COMMODITIES Trial: Initial Dual Oral Therapy vs Monotherapy in PAH With Cardiovascular Comorbidities
Comparison of Initial Dual Oral COMbination Therapy to MOnotherapy in Pulmonary Arterial Hypertension With Cardiovascular comorbiDITIES
Assistance Publique - Hôpitaux de Paris
186 participants
Apr 28, 2026
INTERVENTIONAL
Conditions
Summary
Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with poor prognosis, especially in patients with cardiovascular comorbidities. Current guidelines recommend initial combination therapy, but evidence is lacking for patients with significant comorbidities who are often excluded from clinical trials. The COMMODITIES trial is a multicenter, randomized, controlled study designed to compare the efficacy and safety of initial dual oral combination therapy (tadalafil and ambrisentan) versus oral monotherapy in newly diagnosed PAH patients with at least two cardiovascular comorbidities. The study aims to provide robust evidence to guide treatment strategies in this high-risk population.
Eligibility
Inclusion Criteria16
- Initial PAH diagnosis < 6 months preceding randomisation
- Negative vasoreactivity test
- Treatment-naïve PAH (group 1): idiopathic, heritable, associated with drugs and toxin, associated with connective tissue disease, HIV infection or systemic-to-pulmonary congenital shunt corrected for more than one year
- Meet all of the following hemodynamic criteria by means of a RHC prior to screening:
- mPAP≥25 mmHg and
- PAWP<15 mmHg and
- with PVR≥3 WU
- Presence of at least two of the following criteria, as listed in the European pulmonary hypertension guidelines:
- History of essential hypertension
- Diabetes mellitus (any type)
- Obesity (defined by a BMI ≥30 kg/m2)
- Coronary heart disease (established by any of the following: history of myocardial infarction, history of percutaneous coronary intervention, angiographic evidence of coronary artery disease (>50% stenosis in ≥1 vessel), positive ST, previous coronary artery bypass graft, stable angina)
- Participant able to understand the study procedures
- For women of childbearing potential (WOCBP), effective form of contraception* from screening up to 1 month following discontinuation of the last study treatment
- Affiliation to the french social security regime
- Signed written informed consent
Exclusion Criteria16
- Porto-pulmonary hypertension
- Uncorrected systemic-to-pulmonary congenital shunt
- Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or CT pulmonary angiography
- Patients listed for lung or heart-lung transplantation at time of screening
- Patients on any PAH-specific drug therapy at any time preceding randomisation
- Known moderate-to-severe restrictive lung disease (i.e., total lung capacity < 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second \[FEV1\] < 60% of predicted, with FEV1 / forced vital capacity < 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
- Known or suspected pulmonary veno-occlusive disease (PVOD)
- Severe renal insufficiency (creatinine clearance < 30 mL/min)
- Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 x ULN or serum AST and/or ALT > 3xULN (assessed by local laboratory at screening) and/or Child-Pugh Class C.
- Haemoglobin < 10 g/dL
- Patient under guardianship curatorship, deprived of liberty
- Pregnant women, or breast-feeding women
- Treatment with other PDE-5i for erectile dysfunction
- Ongoing or planned treatment with nitrates and/or doxazosin.
- Ongoing or planned treatment with riociguat
- Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤28 days preceding randomisation
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Interventions
Oral phosphodiesterase-5 inhibitor. Initiated at 20 mg once daily for 7 days, then increased to 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated.
Oral endothelin receptor antagonist. Initiated at 5 mg once daily for 4 weeks, then increased to 10 mg once daily (2 × 5 mg tablets). Dose may be maintained at 5 mg once daily in case of intolerance.
Matching placebo for ambrisentan, 2 tablets once daily, identical in appearance to active drug.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07245680