Comparison of Initial Dual Oral COMbination Therapy to MOnotherapy in Pulmonary Arterial Hypertension With Cardiovascular comorbiDITIES
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.
• 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