array(40) {
  ["project_status"]=>
  string(7) "ongoing"
  ["project_assoc_trials"]=>
  array(17) {
    [0]=>
    object(WP_Post)#5865 (24) {
      ["ID"]=>
      int(1835)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-12-05 15:47:00"
      ["post_date_gmt"]=>
      string(19) "2019-12-05 15:47:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(202) "NCT01743001 - A Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group, Phase 3 Study to Evaluate the Effects of Macitentan on Exercise Capacity in Subjects With Eisenmenger Syndrome"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(193) "nct01743001-a-multi-center-double-blind-randomized-placebo-controlled-parallel-group-phase-3-study-to-evaluate-the-effects-of-macitentan-on-exercise-capacity-in-subjects-with-eisenmenger-syndro"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-10-28 13:56:03"
      ["post_modified_gmt"]=>
      string(19) "2025-10-28 17:56:03"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(242) "https://dev-yoda.pantheonsite.io/clinical-trial/nct01743001-a-multi-center-double-blind-randomized-placebo-controlled-parallel-group-phase-3-study-to-evaluate-the-effects-of-macitentan-on-exercise-capacity-in-subjects-with-eisenmenger-syndro/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [1]=>
    object(WP_Post)#5861 (24) {
      ["ID"]=>
      int(1927)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2023-08-05 04:45:03"
      ["post_date_gmt"]=>
      string(19) "2023-08-05 04:45:03"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(201) "NCT02382016 - A Randomized, Double-blind, Placebo-controlled, Prospective, Multicenter, Parallel Group Study to Assess the Safety and Efficacy of Macitentan in Patients With Portopulmonary Hypertension"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(193) "nct02382016-a-randomized-double-blind-placebo-controlled-prospective-multicenter-parallel-group-study-to-assess-the-safety-and-efficacy-of-macitentan-in-patients-with-portopulmonary-hypertensio"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-14 14:27:39"
      ["post_modified_gmt"]=>
      string(19) "2025-05-14 18:27:39"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(242) "https://dev-yoda.pantheonsite.io/clinical-trial/nct02382016-a-randomized-double-blind-placebo-controlled-prospective-multicenter-parallel-group-study-to-assess-the-safety-and-efficacy-of-macitentan-in-patients-with-portopulmonary-hypertensio/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [2]=>
    object(WP_Post)#5856 (24) {
      ["ID"]=>
      int(17844)
      ["post_author"]=>
      string(4) "1885"
      ["post_date"]=>
      string(19) "2025-08-29 11:01:37"
      ["post_date_gmt"]=>
      string(19) "2025-08-29 15:01:37"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(261) "NCT02021292 - Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel-group, 24-week Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (MERIT-1)"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(191) "nct02021292-prospective-randomized-placebo-controlled-double-blind-multicenter-parallel-group-24-week-study-to-assess-the-efficacy-safety-and-tolerability-of-macitentan-in-subjects-with-inope"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-09-03 13:27:53"
      ["post_modified_gmt"]=>
      string(19) "2025-09-03 17:27:53"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(60) "https://yoda.yale.edu/?post_type=clinical_trial&p=17844"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [3]=>
    object(WP_Post)#5860 (24) {
      ["ID"]=>
      int(17773)
      ["post_author"]=>
      string(4) "1885"
      ["post_date"]=>
      string(19) "2025-08-12 12:55:34"
      ["post_date_gmt"]=>
      string(19) "2025-08-12 16:55:34"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(174) "NCT02558231 - The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (TRITON)"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(170) "nct02558231-the-efficacy-and-safety-of-initial-triple-versus-initial-dual-oral-combination-therapy-in-patients-with-newly-diagnosed-pulmonary-arterial-hypertension-triton"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2026-03-26 16:45:03"
      ["post_modified_gmt"]=>
      string(19) "2026-03-26 20:45:03"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(60) "https://yoda.yale.edu/?post_type=clinical_trial&p=17773"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [4]=>
    object(WP_Post)#5859 (24) {
      ["ID"]=>
      int(17834)
      ["post_author"]=>
      string(4) "1885"
      ["post_date"]=>
      string(19) "2025-08-28 10:27:02"
      ["post_date_gmt"]=>
      string(19) "2025-08-28 14:27:02"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(221) "NCT00367770 - A Multi-Center, Open-Label Extension Study to Protocol AC-052-405 to Evaluate the Safety and Efficacy of Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(195) "nct00367770-a-multi-center-open-label-extension-study-to-protocol-ac-052-405-to-evaluate-the-safety-and-efficacy-of-tracleer-bosentan-in-patients-with-pulmonary-arterial-hypertension-related-to-e"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-09-03 13:24:11"
      ["post_modified_gmt"]=>
      string(19) "2025-09-03 17:24:11"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(60) "https://yoda.yale.edu/?post_type=clinical_trial&p=17834"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [5]=>
    object(WP_Post)#5858 (24) {
      ["ID"]=>
      int(17835)
      ["post_author"]=>
      string(4) "1885"
      ["post_date"]=>
      string(19) "2025-08-28 10:31:57"
      ["post_date_gmt"]=>
      string(19) "2025-08-28 14:31:57"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(246) "A double-blind, randomized, placebo-controlled study to assess the effect of Tracleer™ (bosentan) in combination with the initiation of epoprostenol therapy on cardiopulmonary hemodynamics in patients with severe pulmonary arterial hypertension"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(186) "a-double-blind-randomized-placebo-controlled-study-to-assess-the-effect-of-tracleer-bosentan-in-combination-with-the-initiation-of-epoprostenol-therapy-on-cardiopulmonary-hemodynamics-in"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-08-28 10:31:58"
      ["post_modified_gmt"]=>
      string(19) "2025-08-28 14:31:58"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(60) "https://yoda.yale.edu/?post_type=clinical_trial&p=17835"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [6]=>
    object(WP_Post)#5866 (24) {
      ["ID"]=>
      int(1831)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-12-05 14:58:00"
      ["post_date_gmt"]=>
      string(19) "2019-12-05 14:58:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(248) "NCT00313222 - Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Bosentan in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(192) "nct00313222-prospective-randomized-placebo-controlled-double-blind-multicenter-parallel-group-study-to-assess-the-efficacy-safety-and-tolerability-of-bosentan-in-patients-with-inoperable-chron"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-12 16:16:42"
      ["post_modified_gmt"]=>
      string(19) "2025-05-12 20:16:42"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(241) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00313222-prospective-randomized-placebo-controlled-double-blind-multicenter-parallel-group-study-to-assess-the-efficacy-safety-and-tolerability-of-bosentan-in-patients-with-inoperable-chron/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [7]=>
    object(WP_Post)#5868 (24) {
      ["ID"]=>
      int(1797)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-05-20 16:51:00"
      ["post_date_gmt"]=>
      string(19) "2019-05-20 16:51:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(214) "NCT00091715 - A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Bosentan in Patients With Mildly Symptomatic Pulmonary Arterial Hypertension (PAH)"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(193) "nct00091715-a-randomized-double-blind-placebo-controlled-multicenter-study-to-assess-the-efficacy-safety-and-tolerability-of-bosentan-in-patients-with-mildly-symptomatic-pulmonary-arterial-hype"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-12 16:01:51"
      ["post_modified_gmt"]=>
      string(19) "2025-05-12 20:01:51"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(242) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00091715-a-randomized-double-blind-placebo-controlled-multicenter-study-to-assess-the-efficacy-safety-and-tolerability-of-bosentan-in-patients-with-mildly-symptomatic-pulmonary-arterial-hype/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [8]=>
    object(WP_Post)#5869 (24) {
      ["ID"]=>
      int(1795)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-05-20 16:44:00"
      ["post_date_gmt"]=>
      string(19) "2019-05-20 16:44:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(301) "NCT00303459 - Effects of Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Morbidity and Mortality in Symptomatic Patients With Pulmonary Arterial Hypertension - A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Prospective, Event Driven Phase IV Study"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(195) "nct00303459-effects-of-combination-of-bosentan-and-sildenafil-versus-sildenafil-monotherapy-on-morbidity-and-mortality-in-symptomatic-patients-with-pulmonary-arterial-hypertension-a-multicenter-d"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-12 15:58:57"
      ["post_modified_gmt"]=>
      string(19) "2025-05-12 19:58:57"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(244) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00303459-effects-of-combination-of-bosentan-and-sildenafil-versus-sildenafil-monotherapy-on-morbidity-and-mortality-in-symptomatic-patients-with-pulmonary-arterial-hypertension-a-multicenter-d/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [9]=>
    object(WP_Post)#5862 (24) {
      ["ID"]=>
      int(8011)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2023-08-05 04:44:39"
      ["post_date_gmt"]=>
      string(19) "2023-08-05 04:44:39"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(246) "NCT03078907 - A Multi-center, Double-blind, Placebo-controlled Phase 4 Study in Patients With Pulmonary Arterial Hypertension to Assess the Effect of Selexipag on Daily Life Physical Activity and Patient's Self-reported Symptoms and Their Impacts"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(196) "nct03078907-a-multi-center-double-blind-placebo-controlled-phase-4-study-in-patients-with-pulmonary-arterial-hypertension-to-assess-the-effect-of-selexipag-on-daily-life-physical-activity-and-pati"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-13 17:19:13"
      ["post_modified_gmt"]=>
      string(19) "2025-05-13 21:19:13"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(245) "https://dev-yoda.pantheonsite.io/clinical-trial/nct03078907-a-multi-center-double-blind-placebo-controlled-phase-4-study-in-patients-with-pulmonary-arterial-hypertension-to-assess-the-effect-of-selexipag-on-daily-life-physical-activity-and-pati/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [10]=>
    object(WP_Post)#5864 (24) {
      ["ID"]=>
      int(1838)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-12-05 16:47:00"
      ["post_date_gmt"]=>
      string(19) "2019-12-05 16:47:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(288) "NCT02070991 - A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, 12-week Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(192) "nct02070991-a-prospective-multicenter-double-blind-randomized-placebo-controlled-parallel-group-12-week-study-to-evaluate-the-safety-and-tolerability-of-macitentan-in-subjects-with-combined-pr"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-10-28 13:56:41"
      ["post_modified_gmt"]=>
      string(19) "2025-10-28 17:56:41"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(241) "https://dev-yoda.pantheonsite.io/clinical-trial/nct02070991-a-prospective-multicenter-double-blind-randomized-placebo-controlled-parallel-group-12-week-study-to-evaluate-the-safety-and-tolerability-of-macitentan-in-subjects-with-combined-pr/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [11]=>
    object(WP_Post)#5857 (24) {
      ["ID"]=>
      int(17836)
      ["post_author"]=>
      string(4) "1885"
      ["post_date"]=>
      string(19) "2025-08-28 10:37:32"
      ["post_date_gmt"]=>
      string(19) "2025-08-28 14:37:32"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(256) "NCT00317486 - A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Tracleer (Bosentan) on Oxygen Saturation and Cardiac Hemodynamics in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(193) "nct00317486-a-multi-center-randomized-double-blind-placebo-controlled-study-to-evaluate-the-effects-of-tracleer-bosentan-on-oxygen-saturation-and-cardiac-hemodynamics-in-patients-with-pulmonary"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-08-28 10:39:58"
      ["post_modified_gmt"]=>
      string(19) "2025-08-28 14:39:58"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(60) "https://yoda.yale.edu/?post_type=clinical_trial&p=17836"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [12]=>
    object(WP_Post)#5863 (24) {
      ["ID"]=>
      int(1851)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2020-01-28 14:17:00"
      ["post_date_gmt"]=>
      string(19) "2020-01-28 14:17:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(216) "NCT02471183 - Multicenter, Open-label, Single-group Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Adult Patients With Pulmonary Arterial Hypertension"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(196) "nct02471183-multicenter-open-label-single-group-study-to-assess-the-tolerability-and-the-safety-of-the-transition-from-inhaled-treprostinil-to-oral-selexipag-in-adult-patients-with-pulmonary-arter"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-13 17:17:58"
      ["post_modified_gmt"]=>
      string(19) "2025-05-13 21:17:58"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(245) "https://dev-yoda.pantheonsite.io/clinical-trial/nct02471183-multicenter-open-label-single-group-study-to-assess-the-tolerability-and-the-safety-of-the-transition-from-inhaled-treprostinil-to-oral-selexipag-in-adult-patients-with-pulmonary-arter/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [13]=>
    object(WP_Post)#5867 (24) {
      ["ID"]=>
      int(1798)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-05-20 20:53:00"
      ["post_date_gmt"]=>
      string(19) "2019-05-20 20:53:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(257) "NCT00660179 - A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Phase III Study to Assess the Effects of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(189) "nct00660179-a-multicenter-double-blind-randomized-placebo-controlled-parallel-group-event-driven-phase-iii-study-to-assess-the-effects-of-macitentan-act-064992-on-morbidity-and-mortality-in"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-06-25 16:28:35"
      ["post_modified_gmt"]=>
      string(19) "2025-06-25 20:28:35"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(238) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00660179-a-multicenter-double-blind-randomized-placebo-controlled-parallel-group-event-driven-phase-iii-study-to-assess-the-effects-of-macitentan-act-064992-on-morbidity-and-mortality-in/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [14]=>
    object(WP_Post)#5870 (24) {
      ["ID"]=>
      int(1794)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2019-05-20 16:35:00"
      ["post_date_gmt"]=>
      string(19) "2019-05-20 16:35:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(176) "NCT00319111 - Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT)"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(170) "nct00319111-long-term-open-label-extension-study-in-patients-with-inoperable-chronic-thromboembolic-pulmonary-hypertension-cteph-who-completed-protocol-ac-052-366-benefit"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-05-12 15:57:32"
      ["post_modified_gmt"]=>
      string(19) "2025-05-12 19:57:32"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(219) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00319111-long-term-open-label-extension-study-in-patients-with-inoperable-chronic-thromboembolic-pulmonary-hypertension-cteph-who-completed-protocol-ac-052-366-benefit/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [15]=>
    object(WP_Post)#5871 (24) {
      ["ID"]=>
      int(1727)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2018-10-23 14:23:00"
      ["post_date_gmt"]=>
      string(19) "2018-10-23 14:23:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(198) "NCT01106014 - A Multicenter, Double-blind, Placebo-controlled Phase 3 Study Assessing the Safety and Efficacy of Selexipag on Morbidity and Mortality in Patients With Pulmonary Arterial Hypertension"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(194) "nct01106014-a-multicenter-double-blind-placebo-controlled-phase-3-study-assessing-the-safety-and-efficacy-of-selexipag-on-morbidity-and-mortality-in-patients-with-pulmonary-arterial-hypertension"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2025-10-28 16:08:38"
      ["post_modified_gmt"]=>
      string(19) "2025-10-28 20:08:38"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(243) "https://dev-yoda.pantheonsite.io/clinical-trial/nct01106014-a-multicenter-double-blind-placebo-controlled-phase-3-study-assessing-the-safety-and-efficacy-of-selexipag-on-morbidity-and-mortality-in-patients-with-pulmonary-arterial-hypertension/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [16]=>
    object(WP_Post)#5855 (24) {
      ["ID"]=>
      int(19124)
      ["post_author"]=>
      string(4) "1885"
      ["post_date"]=>
      string(19) "2026-04-16 12:46:56"
      ["post_date_gmt"]=>
      string(19) "2026-04-16 16:46:56"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(222) "NCT03904693 - Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (A-DUE)"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(6) "closed"
      ["ping_status"]=>
      string(6) "closed"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(198) "nct03904693-clinical-study-to-compare-the-efficacy-and-safety-of-macitentan-and-tadalafil-monotherapies-with-the-corresponding-fixed-dose-combination-therapy-in-subjects-with-pulmonary-arterial-hype"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2026-04-16 12:46:56"
      ["post_modified_gmt"]=>
      string(19) "2026-04-16 16:46:56"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(60) "https://yoda.yale.edu/?post_type=clinical_trial&p=19124"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
  }
  ["project_title"]=>
  string(125) "Improving clinical trial efficiency and patient outcomes in pulmonary hypertension: Individual participant data meta-analysis"
  ["project_narrative_summary"]=>
  string(644) "Pulmonary arterial hypertension (PAH) is a rare disease and future PAH trials will require larger sample sizes, longer follow-up time to observe outcomes, and ethical issues related to randomization to placebo. Also, the effectiveness of PAH treatments in different patient profiles remains unknown. We will harmonize individual participant data from the various PAH clinical trials to derive novel surrogate and clinical endpoints, validate innovative clinical trial designs, and determine the treatment effectiveness in specific patient groups. Our research findings will improve the efficiency of PAH clinical trials patient outcomes in PAH."
  ["project_learn_source"]=>
  string(9) "colleague"
  ["principal_investigator"]=>
  array(7) {
    ["first_name"]=>
    string(6) "Steven"
    ["last_name"]=>
    string(5) "Kawut"
    ["degree"]=>
    string(6) "MD, MS"
    ["primary_affiliation"]=>
    string(26) "University of Pennsylvania"
    ["email"]=>
    string(15) "kawut@upenn.edu"
    ["state_or_province"]=>
    string(2) "PA"
    ["country"]=>
    string(13) "United States"
  }
  ["project_key_personnel"]=>
  array(3) {
    [0]=>
    array(6) {
      ["p_pers_f_name"]=>
      string(6) "Nadine"
      ["p_pers_l_name"]=>
      string(10) "Al-Naamani"
      ["p_pers_degree"]=>
      string(7) "MD, MSc"
      ["p_pers_pr_affil"]=>
      string(26) "University of Pennsylvania"
      ["p_pers_scop_id"]=>
      string(0) ""
      ["requires_data_access"]=>
      string(3) "yes"
    }
    [1]=>
    array(6) {
      ["p_pers_f_name"]=>
      string(4) "Jude"
      ["p_pers_l_name"]=>
      string(9) " Moutchia"
      ["p_pers_degree"]=>
      string(7) "MD, MPH"
      ["p_pers_pr_affil"]=>
      string(26) "University of Pennsylvania"
      ["p_pers_scop_id"]=>
      string(0) ""
      ["requires_data_access"]=>
      string(3) "yes"
    }
    [2]=>
    array(6) {
      ["p_pers_f_name"]=>
      string(7) "Breanne"
      ["p_pers_l_name"]=>
      string(8) "McCarthy"
      ["p_pers_degree"]=>
      string(6) "MD, MS"
      ["p_pers_pr_affil"]=>
      string(42) "Hospital of the University of Pennsylvania"
      ["p_pers_scop_id"]=>
      string(0) ""
      ["requires_data_access"]=>
      string(3) "yes"
    }
  }
  ["project_ext_grants"]=>
  array(2) {
    ["value"]=>
    string(2) "no"
    ["label"]=>
    string(68) "No external grants or funds are being used to support this research."
  }
  ["project_date_type"]=>
  string(18) "full_crs_supp_docs"
  ["property_scientific_abstract"]=>
  string(1667) "Background: Pulmonary arterial hypertension (PAH) is a rare disease with significant morbidity and mortality. Clinical trials in PAH are faced with increased costs and duration, requiring innovative trial designs and novel endpoints. Also, treatment and adverse event heterogeneity in PAH remains poorly understood. 



Objectives: We aim to derive and validate novel surrogate endpoints in PAH, to describe the placebo effect in PAH, and to validate the use of external synthetic controls in this population. We also aim to assess treatment pathway and adverse event heterogeneity, to assess the association between PAH concomitant medications with outcomes, and to use machine learning to derive conditional average treatment effects.



Study design: Individual-participant data meta-analyses of PH clinical trials.



Participants: Adult and pediatric participants.



Outcome measures: Primary outcomes include all-cause mortality, clinical worsening, multicomponent clinical improvement, and six-minute walk distance. Secondary outcomes include  hemodynamics, biomarkers, WHO functional class, and quality-of-life measures.



Statistical analysis: We will harmonize and meta-analyze the data using one-step and two-step approaches. Regression modelling including Cox, linear, and logistic regression will be used for inferential analysis. Covariate adjustment or propensity score methods will be used to adjust for confounders. Treatment heterogeneity will be assessed by including interaction terms in the models. Machine learning models will be used determine conditional average treatment effects."
  ["project_brief_bg"]=>
  string(3249) "Multiple pulmonary hypertension (PH) randomized clinical trials (RCTs) have not only led to approved medical options but also generated detailed data on thousands of patients. Meta-analysis of multiple RCTs offers significant benefits beyond analysis of single RCTs. Also, meta-analyses using individual participant data (IPD) provide additional advantages over those using aggregate data such as data harmonization and standardized analysis across trials, and increased power to detect heterogeneity [1, 2].



Future PH RCTs will need to adapt to the current treatment landscape. For example, larger sample size requirements and longer follow-up to demonstrate incremental benefit in patients receiving background therapy, and ethical issues related to randomization to placebo. Trial enrichment, novel clinical trial endpoints, and innovative trial designs are potential solutions. 1.) Identifying robust surrogate outcomes and 2.) multicomponent clinical improvement outcomes would reduce the time required to show benefit on long term outcomes. 3.) The use of external synthetic controls and platform trials would reduce sample size requirements and the length of patient recruitment, and deal with issues related to randomization to placebo.



Current guidelines recommend treatment algorithms for PH [3, 4]. However, 4.) treatment effectiveness and adverse events in specific patient subgroups is not fully known. Treatment and adverse event heterogeneity in PH is poorly studied with significant opportunity to improve precision medicine. 5.) While there are various reasons to consider adjunct therapies in PAH patients such as anti-coagulants, diuretics, beta-blockers, digoxin, and SGLT2 inhibitors, and GLP-1 RAs, their effectiveness remains unknown [3]. 6.) Traditional treatment heterogeneity analyses in PH focus on unique body systems and predict treatment response in siloed pathologies. More wholistic approaches to predict treatment response given a patient’s complete clinical profile are needed.



We have already leveraged IPD from RCTs that were submitted to the United States FDA to address important research questions. Our studies focused on the conduct of clinical trials (minimal clinically important differences for 6MWD [5], assessing potential surrogate end points [6] validating the use of external synthetic controls [7], assessing novel inferential statistics [8]), drive understanding of disease mechanisms (including interactions with the heart [9], liver [10], and kidneys [11]), and aim to improve treatment outcomes (comparative effectiveness analysis [12], assessing treatment heterogeneity [13], uncovering clinical phenotypes for precision medicine [14-16]).



The trials included in our meta-analyses were submitted to the FDA up to 2016. We aim to incorporate contemporary PH clinical trials and other PH clinical trials that were not submitted to the FDA. Updating our PH clinical trial IPD will allow us to update previous analyses where necessary and to address new pertinent research questions as discussed in the aims section. These efforts remain within our overarching goal of improving the conduct of clinical trials and patient outcomes in PH."
  ["project_specific_aims"]=>
  string(1717) "The overarching goal of this project is to improve the efficiency of RCTs and patient outcomes in PH. 



1- To derive and validate a novel multidimensional surrogate end point in PAH

We aim to derive and validate a surrogate outcome in PAH. 



2- To compare multicomponent clinical improvement versus clinical worsening as outcomes in PH RCTs

Investigators have proposed that clinical worsening may not be as “patient focused” as clinical improvement. We aim to derive treatment effect estimates for multicomponent clinical improvement at 12–16 and compare with effect estimates for time to clinical worsening. 



3- To validate the use of synthetic external controls in PAH 

We aim to validate the use of external synthetic controls from historical trials in this patient population.



4- To update treatment effect and heterogeneity analyses in PH

We aim to update our published IPD meta-analyses on treatment effectiveness and heterogeneity [10-16] with novel treatment pathways.



5- To assess the effect of concomitant medications on outcomes in PAH

We aim to assess the association between commonly used concomitant medications in PAH such as anti-coagulants, diuretics, beta-blockers, digoxin, SGLT2 Inhibitors, and GLP-1 RAs with clinical outcomes. 



6- To perform treatment heterogeneity analyses and to develop and validate models to predict individual treatment response

We aim to perform treatment heterogeneity analyses by different clinical subgroups, and to develop and validate models to derive conditional average treatment effects (CATE) given a complete clinical profile."
  ["project_study_design"]=>
  array(2) {
    ["value"]=>
    string(14) "indiv_trial_an"
    ["label"]=>
    string(25) "Individual trial analysis"
  }
  ["project_purposes"]=>
  array(10) {
    [0]=>
    array(2) {
      ["value"]=>
      string(56) "new_research_question_to_examine_treatment_effectiveness"
      ["label"]=>
      string(114) "New research question to examine treatment effectiveness on secondary endpoints and/or within subgroup populations"
    }
    [1]=>
    array(2) {
      ["value"]=>
      string(49) "new_research_question_to_examine_treatment_safety"
      ["label"]=>
      string(49) "New research question to examine treatment safety"
    }
    [2]=>
    array(2) {
      ["value"]=>
      string(76) "confirm_or_validate previously_conducted_research_on_treatment_effectiveness"
      ["label"]=>
      string(76) "Confirm or validate previously conducted research on treatment effectiveness"
    }
    [3]=>
    array(2) {
      ["value"]=>
      string(69) "confirm_or_validate previously_conducted_research_on_treatment_safety"
      ["label"]=>
      string(69) "Confirm or validate previously conducted research on treatment safety"
    }
    [4]=>
    array(2) {
      ["value"]=>
      string(22) "participant_level_data"
      ["label"]=>
      string(36) "Participant-level data meta-analysis"
    }
    [5]=>
    array(2) {
      ["value"]=>
      string(56) "participant_level_data_meta_analysis_from_yoda_and_other"
      ["label"]=>
      string(69) "Meta-analysis using data from the YODA Project and other data sources"
    }
    [6]=>
    array(2) {
      ["value"]=>
      string(37) "develop_or_refine_statistical_methods"
      ["label"]=>
      string(37) "Develop or refine statistical methods"
    }
    [7]=>
    array(2) {
      ["value"]=>
      string(34) "research_on_clinical_trial_methods"
      ["label"]=>
      string(34) "Research on clinical trial methods"
    }
    [8]=>
    array(2) {
      ["value"]=>
      string(28) "research_on_comparison_group"
      ["label"]=>
      string(28) "Research on comparison group"
    }
    [9]=>
    array(2) {
      ["value"]=>
      string(50) "research_on_clinical_prediction_or_risk_prediction"
      ["label"]=>
      string(50) "Research on clinical prediction or risk prediction"
    }
  }
  ["project_research_methods"]=>
  string(1352) "a.) Trials

Phase II, Phase III, and Phase IV RCTs of approved PH therapies that included PH patients are eligible for inclusion. There are no restrictions on reported outcomes or the length of the trial. PH therapies: Endothelin receptor antagonists (Ambrisentan, Macitentan, Sitaxsentan, Bosentan), Phosphodiesterase-5 inhibitors (Sildenafil, Tadalafil), Soluble guanylate cyclase activators (Riociguat), Prostacyclin analogues (Epoprostenol, Treprostinil, Iloprost), Prostacyclin receptor agonists (Selexipag), Activin signaling inhibitor (Sotatercept or ACE-011), and drug combinations. 



We performed a systematic search on MEDLINE (n=751), Embase (n=364), and ClinicalTrials.gov (n = 267) and assessed 936 non-duplicate records for eligibility. We found 56 eligible trials. We have obtained and harmonized IPD for 24 of these trials provided by the United States FDA. Of the 32 other trials, 13 are in the possession of YODA. We have already reached out to the PIs/sponsors of the other trials. The IPD from YODA and from the other trial sponsors will be pooled with the already existing IPD from the FDA and analyzed on the University of Pennsylvania secure servers.



b.) Patients

Adult and pediatric PAH patients participating in these trials are eligible for inclusion. There are no exclusion criteria."
  ["project_main_outcome_measure"]=>
  string(1614) "Data will be harmonized across studies using the definitions and methods that were used to harmonize the existing IPD that were obtained from the FDA, based on Study Data Tabulation Model format. The following outcomes will be analyzed depending on the specific aim.



Primary outcomes: time to all-cause mortality, time to first clinical worsening (defined as any one of the following: all-cause death, hospitalization for worsening PAH, lung transplantation, atrial septostomy, discontinuation of study treatment (or study withdrawal) for worsening PAH, initiation of parenteral prostanoid therapy, or decrease of at least 15% in 6MWD from baseline combined with either worsening of WHO functional class from baseline or the addition of an approved PAH treatment), change in the six-minute walk distance at 12–16 weeks, and multicomponent clinical improvement for aim 2 only (defined as improvement of WHO FC or maintenance of FC I/II; 6MWD increase by ≥33 m or maintenance above 440 m; and reduction in NT-proBNP by ≥30% or maintenance of NT-proBNP <300 ng/L), and other continuous and categorical end points of interest.



Secondary outcomes: Hemodynamics from right heart catheterization (PVR, mRAP, cardiac index, mPAP, and PAWP), blood markers (such as BNP or NTproBNP, liver function tests, kidney function tests), clinical variables (WHO functional class, body mass index, blood pressure, etc.), actigraphy, patient reported outcomes including health-related quality-of-life measures (HRQOL: SF-36/-12, emPHasis-10, MLHF questionnaire, etc.), and adverse events.

"
  ["project_main_predictor_indep"]=>
  string(527) "Aims 1–4 and 6: Randomized treatment arms will be considered ‘active treatment’ or ‘control’, or grouped into treatment pathways based on their mechanism of action including the nitric oxide pathway, endothelin pathway, prostacyclin pathway, activin signaling pathway, combination pathways, placebo, and other pathways as they emerge.



Aim 5: Use of concomitant medications (such as anti-coagulants, diuretics, beta-blockers, digoxin, SGLT2 inhibitors, GLP1 RAs, etc.) at trial baseline.



"
  ["project_other_variables_interest"]=>
  string(633) "Demographic data (age, sex, race and ethnicity, geographical region, etc.), anthropometric data (height, weight, body mass index, body surface area), vital signs (blood pressure, etc.), PH disease data (PH etiology, 6MWD, WHO FC, hemodynamics, HRQOL), blood and urine biomarker data (such as liver function tests [ALT, AST, bilirubin, albumin, etc.], kidney function tests [urea, creatinine, UACR, etc], glucose, cholesterol, triglycerides, etc.), pulmonary function tests [FEV1, FVC, TLC, DLCO], blood gases (PaO2, PaCO2), ECG, echocardiography, actigraphy data, comorbidities, background PH therapies, and concomitant medications. "
  ["project_stat_analysis_plan"]=>
  string(4172) "The IPD data requested from YODA will be harmonized with our current IPD dataset of more than 6,600 patients using the SDTM format. 



We will primarily use the one-step approach to IPD meta-analysis and use the two-step approach as sensitivity analyses, as we have done in multiple prior papers based on harmonized IPD data of PH trials [5-16]. Continuous variables will be summarized as mean (± standard deviation) or median (interquartile range). Categorical variables will be summarized as counts and proportions. 



1.	We will use machine learning feature selection to select variables that potentially lie in the causal pathway of treatment of PH and time to clinical worsening and death. Then we will use dimensionality reduction techniques to reduce the selected input variables into continuous variable (s) that capture a high amount of the variance of the input variables. We will confirm adequate surrogacy (treatment effect on the potential surrogate at 12–16 weeks captures 50% or more of the treatment effect on clinical worsening or mortality, estimated by direct and indirect effects). We will validate the surrogate in a set of holdout clinical trials or perform leave-one out meta-regression to determine how the treatment effect on the surrogate will predict the treatment effect on clinical worsening or mortality in the left-out trial. 



2.	Multivariable logistic regression will be used to obtain the odds ratio of having a multicomponent clinical improvement at 12–16 weeks for each trial. Cox regression will also be used to obtain the hazard ratio of a clinical worsening event for each trial. Log(odds ratio) will be plotted against log(hazard ratio) and a weighted correlation will be calculated (a correlation coefficient of ≥|0.7| will suggest a strong correlation between both outcomes).



3.	The adjusted least-squares mean change from baseline to 12–16 in the six-minute walk distance for the placebo arm of each trial will be calculated and plotted by the trial start date to assess placebo response over time. We will derive external controls for each individual trial from the control arms of the other trials by using the same inclusion/exclusion criteria for the trial. We will then compare the treatment effect when the parent trial controls are used versus the treatment effect when the derived external controls are used. The treatment effect with parent trial controls will be plotted against the treatment effect with the external controls. A strong correlation between both estimates will indicate that the external controls are comparable to the parent trial concurrent controls. Bland Altman plots will also be used to assess agreement.



4.	We will update our previous IPD meta-analyses [10-16] by adding nodes of new treatment pathway (endothelin, prostacyclin, etc.) combinations and update existing nodes with data from contemporary trials and trials that were not submitted to the FDA. We will assess treatment pathway heterogeneity across important subgroups by including interaction terms in the one-step models and plotting treatment pathway effect estimates over values of the variable of interest.



5.	We will perform target trial emulation to compare primary and secondary outcomes in patients who were receiving the concurrent medication at baseline to patients who were not. Propensity scores methods such as matching and inverse probability weighting will be used to adjust for measured covariates.



6.	Treatment effect and adverse event heterogeneity will be assessed by including interaction terms in one-step models and reporting subgroup effects. We will develop machine learning-based models to estimate conditional average treatment effect (CATE) as a function of treatment arm assignment and other clinical profile variables. We will assess multiple machine learning and AI models such as Meta-Learners, Casual Forests, SuperLearner ensemble algorithm, and Deep Learning models. Model fitting and treatment effect estimation will be done using cross-validation to minimize overfitting and optimism bias."
  ["project_software_used"]=>
  array(4) {
    [0]=>
    array(2) {
      ["value"]=>
      string(6) "python"
      ["label"]=>
      string(6) "Python"
    }
    [1]=>
    array(2) {
      ["value"]=>
      string(1) "r"
      ["label"]=>
      string(1) "R"
    }
    [2]=>
    array(2) {
      ["value"]=>
      string(7) "rstudio"
      ["label"]=>
      string(7) "RStudio"
    }
    [3]=>
    array(2) {
      ["value"]=>
      string(5) "stata"
      ["label"]=>
      string(5) "STATA"
    }
  }
  ["project_timeline"]=>
  string(772) "We will begin data harmonization once we receive the IPD from YODA. Data harmonization and cleaning may take up to 6 months. We have already harmonized > 20 studies (some older ones which did not use SDTM format) and have a very established pipeline for matching variables  , especially since the data from YODA will be in STDM format.

We will start data analysis once the data harmonization is completed, working sequentially through the various aims.

We aim to have submitted manuscripts for publication for the all the aforementioned aims within 12–18 months of receiving the IPD from YODA.

We would propose the ability to extend the terms of the DUA as long as we are fulfilling the spirit and criteria for the research collaboration.

"
  ["project_dissemination_plan"]=>
  string(426) "We will present our findings at relevant conferences in the field such as the American Thoracic Society Annual conference or Pulmonary Hypertension Association conference.

We will also publish our findings in high impact respiratory and cardiovascular journals such as the American Journal of Respiratory and Critical Care Medicine, Circulation, the European Heart Journal, and the European Respiratory Journal.

"
  ["project_bibliography"]=>
  string(5139) "

Tierney JF, Riley RD, Smith CT, Clarke M, Stewart LA. Rationale for Embarking on an IPD Meta-Analysis Project. Individual Participant Data Meta‐Analysis; 2021. p. 7-19.
Richard DR, Sofia D, Sarah D, Jayne FT, Lesley AS, Orestis E, David MP. Using individual participant data to improve network meta-analysis projects. BMJ Evidence-Based Medicine 2023; 28: 197.
Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S, Group EESD. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). Eur Heart J 2022; 43: 3618-3731.
Sahay S, Chakinala MM, Kim NH, Preston IR, Thenappan T, McLaughlin VV. Contemporary Treatment of Pulmonary Arterial Hypertension: A U.S. Perspective. Am J Respir Crit Care Med 2024; 210: 581-592.
Moutchia J, McClelland RL, Al-Naamani N, Appleby DH, Blank K, Grinnan D, Holmes JH, Mathai SC, Minhas J, Ventetuolo CE, Zamanian RT, Kawut SM. Minimal Clinically Important Difference in the 6-minute-walk Distance for Patients with Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2023; 207: 1070-1079.
Blette BS, Moutchia J, Al-Naamani N, Ventetuolo CE, Cheng C, Appleby D, Urbanowicz RJ, Fritz J, Mazurek JA, Li F, Kawut SM, Harhay MO. Is low-risk status a surrogate outcome in pulmonary arterial hypertension? An analysis of three randomised trials. Lancet Respir Med 2023; 11: 873-882.
Hsieh J, McClelland R, Pan HM, Minhas J, Appleby D, Urbanowicz R, Holmes J, Fritz JS, Al-Naamani N, Kawut SM, Moutchia J. Synthetic External Controls in Pulmonary Arterial Hypertension (PAH) Using Individual Participant Clinical Trial Data. A14 BUILDING LEGO(LAND): LESSONS LEARNED FROM LARGE SCALE CLINICAL TRIALS IN PAH: American Thoracic Society; 2024. p. A1020-A1020.
Weatherald J, Moutchia J, Al-Naamani N, McClelland RL, Ventetuolo CE, Palevsky HI, Harhay MO, Kawut SM. Win Statistics in Pulmonary Arterial Hypertension Clinical Trials. Am J Respir Crit Care Med 2023; 208: 1231-1234.
Minhas J, Moutchia J, Al-Naamani N, Mazurek JA, Holmes JH, Appleby D, Smith KA, Fritz JS, Pugliese SC, Palevsky HI, Kawut SM. Electrocardiographic Abnormalities and Their Association with Outcomes in Randomized Clinical Trials of Pulmonary Arterial Hypertension. Ann Am Thorac Soc 2024; 21: 858-865.
Scott JV, Moutchia J, McClelland RL, Al-Naamani N, Weinberg E, Palevsky HI, Minhas J, Appleby DK, Smith A, Pugliese SC, Ventetuolo CE, Kawut SM. Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension. Am J Respir Crit Care Med 2024; 210: 1045-1056.
Meservey A, Al-Naamani N, Minhas J, Fritz JS, Appleby D, Kawut SM, Moutchia J. Determinants of Estimated Glomerular Filtration Rate in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension. C62 TOP GUN: NOVEL THERAPEUTICS AND OUTCOMES IN PAH: American Thoracic Society; 2024. p. A6095-A6095.
Moutchia J, McClelland RL, Al-Naamani N, Appleby DH, Holmes JH, Minhas J, Mazurek JA, Palevsky HI, Ventetuolo CE, Kawut SM. Pulmonary arterial hypertension treatment: an individual participant data network meta-analysis. Eur Heart J 2024; 45: 1937-1952.
Hao-Min P, Robyn LM, Jude M, Dina HA, Jason SF, John HH, Jasleen M, Harold IP, Ryan JU, Steven MK, Nadine A-N. Heterogeneity of treatment effects by risk in pulmonary arterial hypertension. Eur Respir J 2023; 62: 2300190.
Ventetuolo CE, Moutchia J, Baird GL, Appleby DH, McClelland RL, Minhas J, Min J, Holmes JH, Urbanowicz RJ, Al-Naamani N, Kawut SM. Baseline Sex Differences in Pulmonary Arterial Hypertension Randomized Clinical Trials. Annals of the American Thoracic Society 2022; 20: 58-66.
McCarthy BE, McClelland RL, Appleby DH, Moutchia JS, Minhas JK, Min J, Mazurek JA, Smith KA, Fritz JS, Pugliese SC, Urbanowicz RJ, Holmes JH, Palevsky HI, Kawut SM, Al-Naamani N. Body mass index and treatment response in patients with pulmonary arterial hypertension: A meta-analysis. Chest 2022.
Kovacs G, Moutchia J, Zeder K, Maron BA, Al-Naamani N, Ventetuolo C, Olschewski H, Kawut SM. Clinical Response to Pulmonary Arterial Hypertension Treatment Does Not Depend on Pulmonary Arterial Wedge Pressure: A Meta-Analysis Using Individual Participant Data from Randomized Clinical Trials. Am J Respir Crit Care Med 2024; 210: 844-847.

"
  ["project_suppl_material"]=>
  bool(false)
  ["project_coi"]=>
  array(4) {
    [0]=>
    array(1) {
      ["file_coi"]=>
      array(21) {
        ["ID"]=>
        int(18804)
        ["id"]=>
        int(18804)
        ["title"]=>
        string(10) "coi_sk.pdf"
        ["filename"]=>
        string(10) "coi_sk.pdf"
        ["filesize"]=>
        int(29380)
        ["url"]=>
        string(59) "https://yoda.yale.edu/wp-content/uploads/2026/02/coi_sk.pdf"
        ["link"]=>
        string(56) "https://yoda.yale.edu/data-request/2026-0136/coi_sk-pdf/"
        ["alt"]=>
        string(0) ""
        ["author"]=>
        string(4) "2326"
        ["description"]=>
        string(0) ""
        ["caption"]=>
        string(0) ""
        ["name"]=>
        string(10) "coi_sk-pdf"
        ["status"]=>
        string(7) "inherit"
        ["uploaded_to"]=>
        int(18803)
        ["date"]=>
        string(19) "2026-02-22 13:18:37"
        ["modified"]=>
        string(19) "2026-02-22 13:18:40"
        ["menu_order"]=>
        int(0)
        ["mime_type"]=>
        string(15) "application/pdf"
        ["type"]=>
        string(11) "application"
        ["subtype"]=>
        string(3) "pdf"
        ["icon"]=>
        string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
      }
    }
    [1]=>
    array(1) {
      ["file_coi"]=>
      array(21) {
        ["ID"]=>
        int(18805)
        ["id"]=>
        int(18805)
        ["title"]=>
        string(10) "coi_jm.pdf"
        ["filename"]=>
        string(10) "coi_jm.pdf"
        ["filesize"]=>
        int(18464)
        ["url"]=>
        string(59) "https://yoda.yale.edu/wp-content/uploads/2026/02/coi_jm.pdf"
        ["link"]=>
        string(56) "https://yoda.yale.edu/data-request/2026-0136/coi_jm-pdf/"
        ["alt"]=>
        string(0) ""
        ["author"]=>
        string(4) "2326"
        ["description"]=>
        string(0) ""
        ["caption"]=>
        string(0) ""
        ["name"]=>
        string(10) "coi_jm-pdf"
        ["status"]=>
        string(7) "inherit"
        ["uploaded_to"]=>
        int(18803)
        ["date"]=>
        string(19) "2026-02-22 13:18:39"
        ["modified"]=>
        string(19) "2026-02-22 13:18:40"
        ["menu_order"]=>
        int(0)
        ["mime_type"]=>
        string(15) "application/pdf"
        ["type"]=>
        string(11) "application"
        ["subtype"]=>
        string(3) "pdf"
        ["icon"]=>
        string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
      }
    }
    [2]=>
    array(1) {
      ["file_coi"]=>
      array(21) {
        ["ID"]=>
        int(19089)
        ["id"]=>
        int(19089)
        ["title"]=>
        string(10) "coi_na.pdf"
        ["filename"]=>
        string(10) "coi_na.pdf"
        ["filesize"]=>
        int(23733)
        ["url"]=>
        string(59) "https://yoda.yale.edu/wp-content/uploads/2026/04/coi_na.pdf"
        ["link"]=>
        string(56) "https://yoda.yale.edu/data-request/2026-0136/coi_na-pdf/"
        ["alt"]=>
        string(0) ""
        ["author"]=>
        string(4) "2326"
        ["description"]=>
        string(0) ""
        ["caption"]=>
        string(0) ""
        ["name"]=>
        string(10) "coi_na-pdf"
        ["status"]=>
        string(7) "inherit"
        ["uploaded_to"]=>
        int(18803)
        ["date"]=>
        string(19) "2026-04-11 19:06:03"
        ["modified"]=>
        string(19) "2026-04-11 19:06:04"
        ["menu_order"]=>
        int(0)
        ["mime_type"]=>
        string(15) "application/pdf"
        ["type"]=>
        string(11) "application"
        ["subtype"]=>
        string(3) "pdf"
        ["icon"]=>
        string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
      }
    }
    [3]=>
    array(1) {
      ["file_coi"]=>
      array(21) {
        ["ID"]=>
        int(20280)
        ["id"]=>
        int(20280)
        ["title"]=>
        string(11) "COI FORM BM"
        ["filename"]=>
        string(15) "COI-FORM-BM.pdf"
        ["filesize"]=>
        int(34150)
        ["url"]=>
        string(64) "https://yoda.yale.edu/wp-content/uploads/2026/02/COI-FORM-BM.pdf"
        ["link"]=>
        string(57) "https://yoda.yale.edu/data-request/2026-0136/coi-form-bm/"
        ["alt"]=>
        string(0) ""
        ["author"]=>
        string(4) "1885"
        ["description"]=>
        string(0) ""
        ["caption"]=>
        string(0) ""
        ["name"]=>
        string(11) "coi-form-bm"
        ["status"]=>
        string(7) "inherit"
        ["uploaded_to"]=>
        int(18803)
        ["date"]=>
        string(19) "2026-10-19 14:03:47"
        ["modified"]=>
        string(19) "2026-10-19 14:03:47"
        ["menu_order"]=>
        int(0)
        ["mime_type"]=>
        string(15) "application/pdf"
        ["type"]=>
        string(11) "application"
        ["subtype"]=>
        string(3) "pdf"
        ["icon"]=>
        string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
      }
    }
  }
  ["data_use_agreement_training"]=>
  bool(true)
  ["human_research_protection_training"]=>
  bool(true)
  ["certification"]=>
  bool(true)
  ["request_data_partner"]=>
  string(15) "johnson-johnson"
  ["request_overridden_res"]=>
  string(1) "3"
  ["search_order"]=>
  string(1) "0"
  ["project_send_email_updates"]=>
  bool(false)
  ["project_publ_available"]=>
  bool(true)
  ["project_year_access"]=>
  string(4) "2026"
  ["project_rep_publ"]=>
  bool(false)
  ["project_assoc_data"]=>
  array(0) {
  }
  ["project_due_dil_assessment"]=>
  array(21) {
    ["ID"]=>
    int(20461)
    ["id"]=>
    int(20461)
    ["title"]=>
    string(55) "YODA Project Due Diligence Assessment 2026-0136_updated"
    ["filename"]=>
    string(59) "YODA-Project-Due-Diligence-Assessment-2026-0136_updated.pdf"
    ["filesize"]=>
    int(142552)
    ["url"]=>
    string(108) "https://yoda.yale.edu/wp-content/uploads/2026/02/YODA-Project-Due-Diligence-Assessment-2026-0136_updated.pdf"
    ["link"]=>
    string(101) "https://yoda.yale.edu/data-request/2026-0136/yoda-project-due-diligence-assessment-2026-0136_updated/"
    ["alt"]=>
    string(0) ""
    ["author"]=>
    string(4) "1885"
    ["description"]=>
    string(0) ""
    ["caption"]=>
    string(0) ""
    ["name"]=>
    string(55) "yoda-project-due-diligence-assessment-2026-0136_updated"
    ["status"]=>
    string(7) "inherit"
    ["uploaded_to"]=>
    int(18803)
    ["date"]=>
    string(19) "2026-11-11 17:28:03"
    ["modified"]=>
    string(19) "2026-11-11 17:28:03"
    ["menu_order"]=>
    int(0)
    ["mime_type"]=>
    string(15) "application/pdf"
    ["type"]=>
    string(11) "application"
    ["subtype"]=>
    string(3) "pdf"
    ["icon"]=>
    string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
  }
  ["project_title_link"]=>
  array(21) {
    ["ID"]=>
    int(20462)
    ["id"]=>
    int(20462)
    ["title"]=>
    string(46) "YODA Project Protocol - 2026-0136 - 2026-10-27"
    ["filename"]=>
    string(46) "YODA-Project-Protocol-2026-0136-2026-10-27.pdf"
    ["filesize"]=>
    int(212744)
    ["url"]=>
    string(95) "https://yoda.yale.edu/wp-content/uploads/2026/02/YODA-Project-Protocol-2026-0136-2026-10-27.pdf"
    ["link"]=>
    string(88) "https://yoda.yale.edu/data-request/2026-0136/yoda-project-protocol-2026-0136-2026-10-27/"
    ["alt"]=>
    string(0) ""
    ["author"]=>
    string(4) "1885"
    ["description"]=>
    string(0) ""
    ["caption"]=>
    string(0) ""
    ["name"]=>
    string(42) "yoda-project-protocol-2026-0136-2026-10-27"
    ["status"]=>
    string(7) "inherit"
    ["uploaded_to"]=>
    int(18803)
    ["date"]=>
    string(19) "2026-11-11 17:28:20"
    ["modified"]=>
    string(19) "2026-11-11 17:28:20"
    ["menu_order"]=>
    int(0)
    ["mime_type"]=>
    string(15) "application/pdf"
    ["type"]=>
    string(11) "application"
    ["subtype"]=>
    string(3) "pdf"
    ["icon"]=>
    string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
  }
  ["project_review_link"]=>
  array(21) {
    ["ID"]=>
    int(20463)
    ["id"]=>
    int(20463)
    ["title"]=>
    string(36) "YODA Project Review - 2026-0136_site"
    ["filename"]=>
    string(38) "YODA-Project-Review-2026-0136_site.pdf"
    ["filesize"]=>
    int(1323153)
    ["url"]=>
    string(87) "https://yoda.yale.edu/wp-content/uploads/2026/02/YODA-Project-Review-2026-0136_site.pdf"
    ["link"]=>
    string(80) "https://yoda.yale.edu/data-request/2026-0136/yoda-project-review-2026-0136_site/"
    ["alt"]=>
    string(0) ""
    ["author"]=>
    string(4) "1885"
    ["description"]=>
    string(0) ""
    ["caption"]=>
    string(0) ""
    ["name"]=>
    string(34) "yoda-project-review-2026-0136_site"
    ["status"]=>
    string(7) "inherit"
    ["uploaded_to"]=>
    int(18803)
    ["date"]=>
    string(19) "2026-11-11 17:28:40"
    ["modified"]=>
    string(19) "2026-11-11 17:28:40"
    ["menu_order"]=>
    int(0)
    ["mime_type"]=>
    string(15) "application/pdf"
    ["type"]=>
    string(11) "application"
    ["subtype"]=>
    string(3) "pdf"
    ["icon"]=>
    string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png"
  }
  ["project_highlight_button"]=>
  string(0) ""
}
data partner
array(1) {
  [0]=>
  string(15) "johnson-johnson"
}


pi country
array(0) {
}


pi affil
array(0) {
}


products
array(3) {
  [0]=>
  string(7) "opsumit"
  [1]=>
  string(7) "uptravi"
  [2]=>
  string(8) "tracleer"
}


num of trials
array(1) {
  [0]=>
  string(2) "17"
}


res
array(1) {
  [0]=>
  string(1) "3"
}