NCT07245680

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

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 186 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance leading to right heart failure and premature death. Although initial combination therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists has demonstrated improved outcomes in patients without major comorbidities, little is known about its benefit-risk balance in patients with cardiovascular comorbidities. The COMMODITIES study is an investigator-initiated, prospective, randomized, controlled, open-label, phase IV trial conducted under European Regulation (EU) 536/2014. The trial will enroll newly diagnosed PAH patients (confirmed by right heart catheterization) who present with at least two cardiovascular comorbidities (including systemic hypertension, diabetes mellitus, coronary artery disease, obesity, or atrial fibrillation). Eligible patients will be randomized 1:1 to receive either: Experimental arm : tadalafil + ambrisentan, Control arm : : tadalafil +placebo. The primary endpoint will be the proportion of patients with PAH and cardiovascular comorbidities who achieve after 6 months a low- or an intermediate-low risk profile according to the noninvasive 4-risk strata method as proposed by the 2022 European pulmonary hypertension guidelines. The total planned sample size is 186, with a study duration of 37 months . Results will provide crucial evidence to inform guideline recommendations and optimize therapeutic strategies in PAH patients with comorbidities.

Conditions

• Pulmonary Arterial Hypertension (PAH)
• Comorbidities
• Cardiovascular Disease (CVD)

Interventions

Type	Name	Description
DRUG	Tadalafil	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.
DRUG	Ambrisentan	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.
DRUG	Placebo (Ambrisentan-matching)	Matching placebo for ambrisentan, 2 tablets once daily, identical in appearance to active drug.

Timeline

• Start date: 2026-01-15
• Primary completion: 2029-02-14
• Completion: 2029-02-14
• First posted: 2025-11-24
• Last updated: 2025-11-24

Locations

1 site across 1 country: France