Initial dual oral therapy versus monotherapy for PAH with cardiovascular comorbidities
Comparison of Initial Dual Oral COMbination Therapy to MOnotherapy in Pulmonary Arterial Hypertension With Cardiovascular comorbiDITIES
This trial will test whether starting both tadalafil and ambrisentan together works better than tadalafil alone for people newly diagnosed with pulmonary arterial hypertension who have at least two heart or vascular health problems.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 186 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Locations | 1 site (Le Kremlin-Bicêtre) |
| Trial ID | NCT07245680 on ClinicalTrials.gov |
What this trial studies
The COMMODITIES trial randomizes newly diagnosed, treatment-naïve group 1 PAH patients with at least two cardiovascular comorbidities to receive either tadalafil plus ambrisentan or tadalafil plus placebo in a 1:1 open-label design. Eligibility requires confirmation by right heart catheterization and a negative vasoreactivity test. The primary outcome is the proportion of patients who reach a low- or intermediate-low risk profile by a noninvasive four-strata method after six months. A total of 186 participants will be followed over a planned 37-month study period to capture safety and short-term risk profile changes.
Who should consider this trial
Good fit: Ideal candidates are newly diagnosed, treatment-naïve group 1 PAH patients confirmed by right heart catheterization within six months who have at least two cardiovascular comorbidities such as hypertension, diabetes, obesity, coronary artery disease, or atrial fibrillation.
Not a fit: Patients with significant left heart disease, a positive vasoreactivity test, prior PAH therapy, or contraindications to endothelin receptor antagonists or PDE-5 inhibitors are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, the trial could show that initial combination oral therapy helps more high-risk PAH patients with cardiovascular comorbidities achieve a lower risk profile at six months, informing treatment guidelines.
How similar studies have performed: Previous trials such as AMBITION demonstrated benefit of initial ambrisentan plus tadalafil in PAH populations without major comorbidities, but patients with multiple cardiovascular comorbidities were often excluded, so this trial addresses that gap.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * 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
Where this trial is running
Le Kremlin-Bicêtre
- Hôpital Bicêtre -Service de pneumologie et soins intensifs respiratoires — Le Kremlin-Bicêtre, France (Recruiting)
Study contacts
- Study coordinator: Laurent SAVALE,, MD, PhD
- Email: laurent.savale@aphp.fr
- Phone: +33 1 45 21 79 08
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.