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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
186
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.
Hôpital Bicêtre -Service de pneumologie et soins intensifs respiratoires
Le Kremlin-Bicêtre, France
RECRUITINGMesurement 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.
Time frame: Week 24
Pulmonary vascular resistance
Change from baseline to Week 24 in pulmonary vascular resistance, assessed by right heart catheterization and expressed in Wood units (WU).
Time frame: week 24
BNP or NT-proBNP
Percent change from baseline to week 24 in BNP or NT-proBNP
Time frame: Week 24
6-Minute Walk Distance (6-MWD)
Change from baseline to week 24 in 6-MWD
Time frame: Week 24
WHO/NYHA Functional class
Proportion of participants who improve in WHO/NYHA FC at the end of the DBPC Treatment period
Time frame: Week 24
TAPSE/systolic pulmonary artery pressure (SPAP) ratio
Change from baseline to week 24 in the TAPSE/systolic pulmonary artery pressure (SPAP) ratio
Time frame: Week 24
Death or Nonfatal Clinical Worsening
Rate of Death or Nonfatal Clinical Worsening defined by hospitalisation for PAH worsening or disease progression defined by worsening of functional class and decrease in 6-min walk distance of more than 15% from baseline, or need for additional specific therapy or lung transplantation
Time frame: Week 24
emPHasis-10 score
Change from baseline to week 24 in the emPHasis-10 score
Time frame: Week 24
EuroQoL-5 dimensions scale 5 levels (EQ-5D-5L)
Change from baseline to week 24 EuroQoL-5 dimensions scale 5 levels (EQ-5D-5L)
Time frame: Week 24
Death
All causes of death
Time frame: Week 24
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