The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension

Completed · Phase 3

Conditions studied: Pulmonary Arterial Hypertension

In brief

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.

Key facts

Study ID

NCT02558231

Run by

Actelion

People needed

247

Starts

2016-05-01

Expected to finish

2020-04-20

Last updated by the study team

2025-03-30

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• UCSD Health Sciences — La Jolla, California, United States
• UCLA Medical Center — Los Angeles, California, United States
• Mayo Clinic Jacksonville — Jacksonville, Florida, United States
• Cleveland Clinic Florida — Weston, Florida, United States
• Piedmont Pulmonary and Critical Care Research — Atlanta, Georgia, United States
• Northwestern University — Chicago, Illinois, United States
• University of Iowa Hospitals & Clinics — Iowa City, Iowa, United States
• Kentuckiana Pulmonary Associates — Louisville, Kentucky, United States
• LSU Health Sciences Center — New Orleans, Louisiana, United States
• Johns Hopkins School of Medicine — Baltimore, Maryland, United States
• Tufts Medical Center — Boston, Massachusetts, United States
• Boston University Medical Center — Boston, Massachusetts, United States
• Washington University School of Medicine — Saint Louis, Michigan, United States
• University of New Mexico Hospital — Albuquerque, New Mexico, United States
• The Christ Hospital — Cincinnati, Ohio, United States
• Allegheny General Hospital of Research — Pittsburgh, Pennsylvania, United States
• UPMC Presbyterian — Pittsburgh, Pennsylvania, United States
• University of Texas Southwestern Medical Center — Dallas, Texas, United States
• Houston Methodist Hospital — Houston, Texas, United States
• Royal Prince Albert Hospital — Camperdown, New South Wales, Australia
• St. Vincents Hospital Sydney — Darlinghurst, New South Wales, Australia
• LKH -Universität Klinkum Graz — Graz, Austria
• Krankenhaus der Elisabethinen Linz — Linz, Austria
• AKH Wien — Vienna, Austria
• Arizona Pulmonary Specialists, LTD — Phoenix, Arizona, United States

Full record on ClinicalTrials.gov

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