Ambrisentan for Early-Stage Low-Risk Pulmonary Arterial Hypertension

BACKGROUND: Early-stage pulmonary arterial hypertension (PAH) with mild hemodynamic abnormalities is increasingly being concerned because of the revised PAH definition. However, there is a lack of randomized controlled trials evaluating the efficacy of currently available medications in this population. OBJECTIVES: The ALEPH (Ambrisentan for Early Low-Risk Pulmonary Arterial Hypertension) trial is designed to investigate the efficacy and safety of ambrisentan in early-stage low-risk PAH patients. METHODS: The ALEPH trial is a multicenter, randomized, double-blind, placebo-controlled clinical study. Eligible patients are diagnosed with PAH according to 2022 European Society of Cardiology and the European Respiratory Society guidelines, with mean pulmonary artery pressure >20 and 2 and ≤3 WUs, and PAWP ≤15 mm Hg by right heart catheterization, classified as low-risk, and have not previously received PAH-specific therapy. Participants are randomly assigned to receive either ambrisentan or placebo for 12 months. The primary endpoint is a composite of PAH progression. Secondary endpoints include changes in hemodynamic and echocardiographic parameters, N-terminal pro-B-type natriuretic peptide levels, World Health Organization functional class, 6-minute walk distance, and time to clinical events such as hospitalization or death. Primary analysis will be performed in the intention-to-treat population, with sensitivity analysis in the per-protocol population. Statistical analyses include Z-test for the primary endpoint, Cox proportional hazards models for time-to-event data, and analysis of covariance or Mann-Whitney U test for continuous variables. CONCLUSIONS: The ALEPH trial aims to generate high-quality evidence regarding the efficacy and safety of ambrisentan monotherapy in early-stage, low-risk PAH. This study may provide valuable insight into early therapeutic intervention for patients with mild hemodynamic disorder. (Ambrisentan for Early Low-Risk Pulmonary Arterial Hypertension [ALEPH]; NCT06987097).