COMMODITIES Trial: Initial Dual Oral Therapy vs Monotherapy in PAH With Cardiovascular Comorbidities

NCT07245680 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: APHP2308472023-509891-40-00
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

PAH; Endothelin Receptor Antagonist (Ambrisentan); Phosphodiesterase-5 Inhibitor (Tadalafil); Cardiovascular Comorbidities; Combination Therapy; Randomized Controlled Trial; Pulmonary arterial hypertension

Outcome Measures

Primary Outcomes (1)

• Mesurement of the risk profile according to the non-invasive 4-risk strata method

  Proportion of patients with PAH and with at least two cardiovascular comorbidities who achieve after 24 week a low- or an intermediate-low risk profile according to the non-invasive 4-risk strata method as proposed by the 2022 european pulmonary hypertension guidelines.

  Week 24

Secondary Outcomes (9)

• Pulmonary vascular resistance

  week 24

• BNP or NT-proBNP

  Week 24

• 6-Minute Walk Distance (6-MWD)

  Week 24

• WHO/NYHA Functional class

  Week 24

• TAPSE/systolic pulmonary artery pressure (SPAP) ratio

  Week 24

Study Arms (2)

Tadalafil + Ambrisentan

EXPERIMENTAL

Tadalafil - 20 mg once daily for 7 days, then 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated. Ambrisentan - 5 mg once daily for 4 weeks, then 10 mg once daily (2 × 5 mg tablets). Dose may be maintained at 5 mg once daily in case of intolerance

Drug: Tadalafil; Drug: Ambrisentan

Tadalafil + Placebo

ACTIVE COMPARATOR

Tadalafil - 20 mg once daily for 7 days, then 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated. Placebo - Matching placebo for ambrisentan, 2 tablets once daily.

Drug: Tadalafil; Drug: Placebo (Ambrisentan-matching)

Interventions

Tadalafil DRUG

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.

Tadalafil + Ambrisentan; Tadalafil + Placebo

Ambrisentan DRUG

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.

Tadalafil + Ambrisentan

Placebo (Ambrisentan-matching) DRUG

Matching placebo for ambrisentan, 2 tablets once daily, identical in appearance to active drug.

Tadalafil + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Bicêtre -Service de pneumologie et soins intensifs respiratoires

Le Kremlin-Bicêtre, 94270, France

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Cardiovascular Diseases

Interventions

Tadalafil; ambrisentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Central Study Contacts

Laurent SAVALE,, MD, PhD

CONTACT

+33 1 45 21 79 08; laurent.savale@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind design: participants and investigators are blinded to treatment allocation. A matching placebo is used in place of ambrisentan to ensure blinding, while tadalafil is given in both arms.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a 1:1 ratio to receive either tadalafil plus ambrisentan or tadalafil plus placebo, in a parallel assignment design with two treatment arms under double-blind masking.

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: November 24, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): February 14, 2029
• Study Completion (Estimated): February 14, 2029
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

FR (1)