Back to resultsThe Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (TRITON)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Macitentan
Tadalafil
Selexipag
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent prior to any study-mandated procedure.
- Male or female ≥ 18 and ≤ 75 years of age at screening.
- Initial PAH diagnosis < 6 months prior to enrollment.
RHC performed between Day -28 and Day 1, meeting all the following criteria:
- Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg.
- Pulmonary artery wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg.
- PVR ≥ 480 dyn•sec/cm5 (≥ 6 Wood Units).
- Negative vasoreactivity test mandatory in idiopathic, heritable, and drug/toxin induced PAH (at this or a previous RHC).
Symptomatic PAH belonging to one of the following subgroups:
- Idiopathic.
- Heritable.
- Drug or toxin induced.
- Associated with one of the following: connective tissue disease; HIV infection; congenital heart disease.
- 6-minute walk distance (6MWD) ≥ 50 m at screening.
- Women of childbearing potential must not be pregnant, must perform regular pregnancy tests, and use reliable contraception.
Exclusion Criteria:
- Any PAH-specific drug therapy at any time.
- Cardio pulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Day 1).
- Body mass index (BMI) > 40 kg/m2 at screening.
Presence of three or more of the following risk factors for heart failure with preserved ejection fraction at screening:
- BMI > 30 kg/m2.
- Diabetes mellitus of any type.
- Essential hypertension.
Coronary artery disease, i.e., any of the following:
- History of stable angina or
- More than 50% stenosis in a coronary artery (by coronary angiography) or
- History of myocardial infarction or
- History of or planned coronary artery bypass grafting and/or coronary artery stenting.
- Acute myocardial infarction ≤ 12 weeks prior to screening.
- Stroke ≤ 12 weeks prior to screening.
- Known permanent atrial fibrillation.
- SBP < 90 mmHg at screening or Day 1.
- Ongoing or planned treatment with organic nitrates and/or doxazosin.
Presence of one or more of the following signs of relevant lung disease at any time up to screening:
- Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% of predicted (eligible only if no or mild interstitial lung disease on computed tomography).
- Forced vital capacity (FVC) < 60% of predicted.
- Forced expiratory volume in one second (FEV1) < 60% of predicted.
- Known or suspected pulmonary veno-occlusive disease (PVOD).
- Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) > ULN (assessed by central laboratory at screening); and/or Child-Pugh Class C.
- Serum AST and/or alanine aminotransferase (ALT) > 3 × ULN (assessed by central laboratory at screening).
- Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min/1.73 m2) assessed by central laboratory at screening.
- Ongoing or planned dialysis.
- Hemoglobin < 100 g/L assessed by central laboratory at screening.
- Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism).
- Loss of vision in one or both eyes because of non-arteritic ischemic optic neuropathy (NAION).
- Treatment with strong inducers of cytochrome P450 3A4 (CYP3A4; e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤ 28 days prior to Day 1.
- Treatment with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) and/or strong inhibitors of CYP2C8 (e.g., gemfibrozil) ≤ 28 days prior to Day 1.
- Treatment with another investigational drug (planned, or taken ≤ 12 weeks prior to Day 1).
- Hypersensitivity to any of the 3 study treatments or any excipient of their formulations.
- Pregnancy, breastfeeding, or intention to become pregnant during the study.
- Concomitant life-threatening disease with a life expectancy < 12 months.
- Alcohol abuse.
- Any factor or condition likely to affect protocol compliance of the subject, as judged by the investigator.
Sites / Locations
- Arizona Pulmonary Specialists, LTD
- UCSD Health Sciences
- UCLA Medical Center
- Mayo Clinic Jacksonville
- Cleveland Clinic Florida
- Piedmont Pulmonary and Critical Care Research
- Northwestern University
- University of Iowa Hospitals & Clinics
- Kentuckiana Pulmonary Associates
- LSU Health Sciences Center
- Johns Hopkins School of Medicine
- Tufts Medical Center
- Boston University Medical Center
- Washington University School of Medicine
- University of New Mexico Hospital
- The Christ Hospital
- Allegheny General Hospital of Research
- UPMC Presbyterian
- University of Texas Southwestern Medical Center
- Houston Methodist Hospital
- Royal Prince Albert Hospital
- St. Vincents Hospital Sydney
- LKH -Universität Klinkum Graz
- Krankenhaus der Elisabethinen Linz
- AKH Wien
- Hôpital Erasme
- UZ Leuven - Campus Gasthuisberg
- Vancouver General Hospital
- London Health Sciences Centre - Victoria Hospital
- University of Toronto
- Jewish General Hospital
- Institut Universitaire de Cardiologie et de Pneumologie de Québec
- University of Calgary
- University of Ottawa Heart Institute
- Aarhus University Hospital Skejby
- Rigshospitalet Copenhagen
- CHU de Bicêtre
- Unversitätsklinikum Carl Gustav Carus
- Universitätsklinikum Giessen
- Universitätsklinikum Hamburg-Eppendorf
- Medizinische Hochschule Hannover
- Universitätsklinikum Heidelberg
- Universitätsklinikum Köln
- Universitätsklinikum Regensburg
- Mater Misericordiae University Hospital
- Ospedale Sant'Orsola
- VUmc Amsterdam
- Maastricht University Medical Center
- Hospital Clinic de Barcelona
- Hospital 12 de Octubre
- Skånes universitetssjukhus Lund
- Norrlands universitetssjukhus
- Kardiologkliniken
- Universiätsspital Zürich
- Golden Jubilee National Hospital
- The Royal Free Hospital
- Royal Brompton Hospital
- Hammersmith Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Triple oral combination treatment
Dual oral combination treatment
Arm Description
Macitentan, tadalafil, and selexipag
Macitentan, tadalafil, and placebo
Outcomes
Primary Outcome Measures
Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR)
Change from baseline to Week 26 in PVR was expressed as the ratio of Week 26 to baseline PVR value (Week 26 divided by baseline) using re-calculated PVR. PVR was determined by right heart catheterization (RHC). A geometric least square mean ratio of Week 26 to baseline PVR less than (<) 1 corresponds to a reduction in PVR from baseline. Missing values were imputed using a last observation carried forward (LOCF) approach.
Secondary Outcome Measures
Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD)
The change from baseline to Week 26 in 6MWD was calculated as Week 26 minus baseline. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. Missing values were imputed using a LOCF approach.
Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels
The change from baseline to Week 26 in NT-proBNP was expressed as the ratio of Week 26 to baseline NT-proBNP (Week 26 divided by baseline). A geometric least square mean ratio of Week 26 to baseline NT-proBNP <1 corresponds to a reduction in NT-proBNP from baseline. Missing values were imputed using a LOCF approach.
Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC)
WHO FC is a classification graded from Class I to IV which reflects disease severity based on symptoms. Worsening was defined as death or hospitalization due to PAH. Class I: No limitation of activity; Class II: slight limitation with ordinary activities; Class III: may not have symptoms at rest but greatly limited activities; Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Missing values were imputed using a LOCF approach.
Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP)
Change from baseline to Week 26 in mean Pulmonary Arterial Pressure (mPAP) was measured. The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Missing values were imputed using a LOCF approach.
Change From Baseline to Week 26 in Mean Right Atrial Pressure (mRAP)
Change from baseline to Week 26 in mean Right Atrial Pressure (mRAP) was measured. Missing values were imputed using a LOCF approach.
Change From Baseline to Week 26 in Total Pulmonary Resistance
Change from baseline to Week 26 in total pulmonary resistance was measured. Total pulmonary resistance was calculated as mPAP/CO*80, where CO is cardiac output. Re-calculated values were used for analysis and missing values were imputed using a LOCF approach.
Change From Baseline to Week 26 in Cardiac Index
Change from baseline to Week 26 in cardiac index was measured. Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Re-calculated values were used for analysis and missing values were imputed using a LOCF approach.
Change From Baseline to Week 26 in Venous Oxygen Saturation (%)
Change from baseline to Week 26 in venous oxygen saturation was measured. Missing values were imputed using a LOCF approach.
Number of Participants With Disease Progression Event
Number of participants with disease progression event were reported. Disease progression event as adjudicated by the CEC, defined as any of the following: a. Death (all causes; adjudicated for PAH relationship); b. Hospitalization for worsening PAH; c. Initiation of prostacyclin, a prostacyclin analog, or a prostacyclin receptor agonist for worsening PAH; d. Clinical worsening defined as a post-baseline decrease in 6MWD by more than (>) 15 percent (%) from the highest 6MWD obtained at or after baseline, accompanied by WHO FC III or IV (both conditions confirmed at two consecutive post-baseline visits separated by 1-21 days).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02558231
Brief Title
The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
Acronym
TRITON
Official Title
The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Placebo-controlled, Phase 3b Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
May 1, 2016 (Actual)
Primary Completion Date
August 29, 2019 (Actual)
Study Completion Date
April 20, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of this clinical trial is to compare the efficacy and safety of an initial triple oral treatment regimen (macitentan, tadalafil, selexipag) versus an initial dual oral treatment regimen (macitentan, tadalafil, placebo) in newly diagnosed, treatment-naïve patients with pulmonary arterial hypertension.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
247 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Triple oral combination treatment
Arm Type
Experimental
Arm Description
Macitentan, tadalafil, and selexipag
Arm Title
Dual oral combination treatment
Arm Type
Placebo Comparator
Arm Description
Macitentan, tadalafil, and placebo
Intervention Type
Drug
Intervention Name(s)
Macitentan
Intervention Description
Used open-label in both arms, 10 mg tablet, 1 tablet u.i.d.
Intervention Type
Drug
Intervention Name(s)
Tadalafil
Intervention Description
Used open-label in both arms, 20 mg tablet, 1-2 tablets u.i.d.
Intervention Type
Drug
Intervention Name(s)
Selexipag
Intervention Description
Used double-blind in the triple oral treatment arm, 200 microgram tablet, 1-8 tablets b.i.d.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR)
Description
Change from baseline to Week 26 in PVR was expressed as the ratio of Week 26 to baseline PVR value (Week 26 divided by baseline) using re-calculated PVR. PVR was determined by right heart catheterization (RHC). A geometric least square mean ratio of Week 26 to baseline PVR less than (<) 1 corresponds to a reduction in PVR from baseline. Missing values were imputed using a last observation carried forward (LOCF) approach.
Time Frame
Baseline, Week 26
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD)
Description
The change from baseline to Week 26 in 6MWD was calculated as Week 26 minus baseline. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. Missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels
Description
The change from baseline to Week 26 in NT-proBNP was expressed as the ratio of Week 26 to baseline NT-proBNP (Week 26 divided by baseline). A geometric least square mean ratio of Week 26 to baseline NT-proBNP <1 corresponds to a reduction in NT-proBNP from baseline. Missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC)
Description
WHO FC is a classification graded from Class I to IV which reflects disease severity based on symptoms. Worsening was defined as death or hospitalization due to PAH. Class I: No limitation of activity; Class II: slight limitation with ordinary activities; Class III: may not have symptoms at rest but greatly limited activities; Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Missing values were imputed using a LOCF approach.
Time Frame
Week 26
Title
Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP)
Description
Change from baseline to Week 26 in mean Pulmonary Arterial Pressure (mPAP) was measured. The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Change From Baseline to Week 26 in Mean Right Atrial Pressure (mRAP)
Description
Change from baseline to Week 26 in mean Right Atrial Pressure (mRAP) was measured. Missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Change From Baseline to Week 26 in Total Pulmonary Resistance
Description
Change from baseline to Week 26 in total pulmonary resistance was measured. Total pulmonary resistance was calculated as mPAP/CO*80, where CO is cardiac output. Re-calculated values were used for analysis and missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Change From Baseline to Week 26 in Cardiac Index
Description
Change from baseline to Week 26 in cardiac index was measured. Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Re-calculated values were used for analysis and missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Change From Baseline to Week 26 in Venous Oxygen Saturation (%)
Description
Change from baseline to Week 26 in venous oxygen saturation was measured. Missing values were imputed using a LOCF approach.
Time Frame
Baseline, Week 26
Title
Number of Participants With Disease Progression Event
Description
Number of participants with disease progression event were reported. Disease progression event as adjudicated by the CEC, defined as any of the following: a. Death (all causes; adjudicated for PAH relationship); b. Hospitalization for worsening PAH; c. Initiation of prostacyclin, a prostacyclin analog, or a prostacyclin receptor agonist for worsening PAH; d. Clinical worsening defined as a post-baseline decrease in 6MWD by more than (>) 15 percent (%) from the highest 6MWD obtained at or after baseline, accompanied by WHO FC III or IV (both conditions confirmed at two consecutive post-baseline visits separated by 1-21 days).
Time Frame
Week 26, Month 12, Month 18, Month 24, Month 30, and End of Analysis Period (up to 40 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent prior to any study-mandated procedure.
Male or female ≥ 18 and ≤ 75 years of age at screening.
Initial PAH diagnosis < 6 months prior to enrollment.
RHC performed between Day -28 and Day 1, meeting all the following criteria:
Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg.
Pulmonary artery wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg.
PVR ≥ 480 dyn•sec/cm5 (≥ 6 Wood Units).
Negative vasoreactivity test mandatory in idiopathic, heritable, and drug/toxin induced PAH (at this or a previous RHC).
Symptomatic PAH belonging to one of the following subgroups:
Idiopathic.
Heritable.
Drug or toxin induced.
Associated with one of the following: connective tissue disease; HIV infection; congenital heart disease.
6-minute walk distance (6MWD) ≥ 50 m at screening.
Women of childbearing potential must not be pregnant, must perform regular pregnancy tests, and use reliable contraception.
Exclusion Criteria:
Any PAH-specific drug therapy at any time.
Cardio pulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Day 1).
Body mass index (BMI) > 40 kg/m2 at screening.
Presence of three or more of the following risk factors for heart failure with preserved ejection fraction at screening:
BMI > 30 kg/m2.
Diabetes mellitus of any type.
Essential hypertension.
Coronary artery disease, i.e., any of the following:
History of stable angina or
More than 50% stenosis in a coronary artery (by coronary angiography) or
History of myocardial infarction or
History of or planned coronary artery bypass grafting and/or coronary artery stenting.
Acute myocardial infarction ≤ 12 weeks prior to screening.
Stroke ≤ 12 weeks prior to screening.
Known permanent atrial fibrillation.
SBP < 90 mmHg at screening or Day 1.
Ongoing or planned treatment with organic nitrates and/or doxazosin.
Presence of one or more of the following signs of relevant lung disease at any time up to screening:
Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% of predicted (eligible only if no or mild interstitial lung disease on computed tomography).
Forced vital capacity (FVC) < 60% of predicted.
Forced expiratory volume in one second (FEV1) < 60% of predicted.
Known or suspected pulmonary veno-occlusive disease (PVOD).
Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) > ULN (assessed by central laboratory at screening); and/or Child-Pugh Class C.
Serum AST and/or alanine aminotransferase (ALT) > 3 × ULN (assessed by central laboratory at screening).
Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min/1.73 m2) assessed by central laboratory at screening.
Ongoing or planned dialysis.
Hemoglobin < 100 g/L assessed by central laboratory at screening.
Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism).
Loss of vision in one or both eyes because of non-arteritic ischemic optic neuropathy (NAION).
Treatment with strong inducers of cytochrome P450 3A4 (CYP3A4; e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤ 28 days prior to Day 1.
Treatment with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) and/or strong inhibitors of CYP2C8 (e.g., gemfibrozil) ≤ 28 days prior to Day 1.
Treatment with another investigational drug (planned, or taken ≤ 12 weeks prior to Day 1).
Hypersensitivity to any of the 3 study treatments or any excipient of their formulations.
Pregnancy, breastfeeding, or intention to become pregnant during the study.
Concomitant life-threatening disease with a life expectancy < 12 months.
Alcohol abuse.
Any factor or condition likely to affect protocol compliance of the subject, as judged by the investigator.
Facility Information:
Facility Name
Arizona Pulmonary Specialists, LTD
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
UCSD Health Sciences
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Cleveland Clinic Florida
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Piedmont Pulmonary and Critical Care Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Iowa Hospitals & Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Kentuckiana Pulmonary Associates
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
LSU Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Johns Hopkins School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111-1552
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118-2526
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Michigan
ZIP/Postal Code
63110
Country
United States
Facility Name
University of New Mexico Hospital
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219-2906
Country
United States
Facility Name
Allegheny General Hospital of Research
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
UPMC Presbyterian
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8550
Country
United States
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Royal Prince Albert Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
St. Vincents Hospital Sydney
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
LKH -Universität Klinkum Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Krankenhaus der Elisabethinen Linz
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
AKH Wien
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Hôpital Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
UZ Leuven - Campus Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
London Health Sciences Centre - Victoria Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Institut Universitaire de Cardiologie et de Pneumologie de Québec
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
University of Calgary
City
Calgary
ZIP/Postal Code
T1Y 6J4
Country
Canada
Facility Name
University of Ottawa Heart Institute
City
Ottawa
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
Aarhus University Hospital Skejby
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Rigshospitalet Copenhagen
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
CHU de Bicêtre
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94270
Country
France
Facility Name
Unversitätsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Giessen
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Universitätsklinikum Köln
City
Köln
ZIP/Postal Code
50924
Country
Germany
Facility Name
Universitätsklinikum Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Mater Misericordiae University Hospital
City
Dublin
ZIP/Postal Code
D07 R2WY
Country
Ireland
Facility Name
Ospedale Sant'Orsola
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
VUmc Amsterdam
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Maastricht University Medical Center
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Skånes universitetssjukhus Lund
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Norrlands universitetssjukhus
City
Umeå
ZIP/Postal Code
901 85
Country
Sweden
Facility Name
Kardiologkliniken
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Universiätsspital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Golden Jubilee National Hospital
City
Clydebank
ZIP/Postal Code
G81 4DY
Country
United Kingdom
Facility Name
The Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
34593120
Citation
Chin KM, Sitbon O, Doelberg M, Feldman J, Gibbs JSR, Grunig E, Hoeper MM, Martin N, Mathai SC, McLaughlin VV, Perchenet L, Poch D, Saggar R, Simonneau G, Galie N. Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary Arterial Hypertension. J Am Coll Cardiol. 2021 Oct 5;78(14):1393-1403. doi: 10.1016/j.jacc.2021.07.057.
Results Reference
derived
Learn more about this trial
The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
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