Phase 3
Completed N=247
The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
Source: ClinicalTrials.gov NCT02558231 ↗Enrolled (actual)
247
Serious AEs
43.1%
Results posted
Sep 2020
Primary outcomePrimary: Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR) — 0.46; 0.48 ratio — p=0.4239
◆ Published Evidence
Highly cited
165citations · ~33 / year
Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary Arterial Hypertension.
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.
Linked Publications
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Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary Arterial Hypertension.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR) |
0.46; 0.48 | 0.4239 |
| SECONDARY Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) |
54.96; 56.39 | 0.8758 |
| SECONDARY Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels |
0.26; 0.25 | 0.8529 |
| SECONDARY Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC) |
99.2; 97.5 | — |
| SECONDARY Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP) |
-12.92; -12.20 | 0.4998 |
| SECONDARY Change From Baseline to Week 26 in Mean Right Atrial Pressure (mRAP) |
-1.78; -1.69 | 0.8528 |
| SECONDARY Change From Baseline to Week 26 in Total Pulmonary Resistance |
-511.88; -514.28 | 0.9474 |
| SECONDARY Change From Baseline to Week 26 in Cardiac Index |
0.97; 0.84 | 0.1902 |
| SECONDARY Change From Baseline to Week 26 in Venous Oxygen Saturation (%) |
5.59; 6.79 | 0.1227 |
| SECONDARY Number of Participants With Disease Progression Event |
8; 13; 13; 20; 15; 23 | 0.0867 |
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 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 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.
Data sourced from ClinicalTrials.gov (NCT02558231) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.