BACKGROUND: Adaptation of the right ventricle is a key determinant of outcomes in pulmonary arterial hypertension (PAH). Despite a compelling rationale to develop targeted therapies for the right ventricle in PAH, no such treatments exist. H RESEARCH QUESTION: Do H STUDY DESIGN AND METHODS: We conducted a 24-week, single-center, 1:1 randomized, double-masked, placebo-controlled trial of the H RESULTS: From May 2019 through July 2023, 80 participants were randomized with 79 receiving study drug. No significant difference in the primary outcome of 6MWD at 24 weeks was found, with an increase of 4.7 m seen in the placebo arm vs a decrease of 17.0 m in the famotidine arm (P = .24). Also no differences were found in secondary end points at 24 weeks. Study drug was well tolerated, and safety profiles were similar between arms. Adherence and study conduct were good overall. Participants with methamphetamine-associated PAH were similar in all aspects to the study participants more broadly. INTERPRETATION: The results of this trial do not support the routine use of famotidine 20 mg/d as an adjunct therapy for the treatment of PAH. The findings of the Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension trial argue against the practice of avoiding participants with methamphetamine-associated PAH in randomized clinical trials of novel therapies. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov
No.: NCT03554291
URL: www. CLINICALTRIALS: gov.