Rationale and design of the ranolazine PH-RV study: a multicentred randomised and placebo-controlled study of ranolazine to improve RV function in patients with non-group 2 pulmonary hypertension

Yuchi Han, Paul R Forfia, Anjali Vaidya, Jeremy A Mazurek, Myung H Park, Gautam Ramani, Stephen Y Chan, Aaron B Waxman, Yuchi Han, Paul R Forfia, Anjali Vaidya, Jeremy A Mazurek, Myung H Park, Gautam Ramani, Stephen Y Chan, Aaron B Waxman

Abstract

Introduction: A major determining factor on outcomes in patients with pulmonary arterial hypertension (PAH) is right ventricular (RV) function. Ranolazine, which is currently approved for chronic stable angina, has been shown to improve RV function in an animal model and has been shown to be safe in small human studies with PAH. We aim to study the effect of ranolazine on RV function using cardiovascular magnetic resonance (CMR) in patients with pulmonary hypertension (non-group 2 patients) and monitor the effect of ranolazine on metabolism using metabolic profiling and changes of microRNA.

Methods and analysis: This study is a longitudinal, randomised, double-blind, placebo-controlled, multicentre proof-of-concept study in 24 subjects with pulmonary hypertension and RV dysfunction treated with ranolazine over 6 months. Subjects who meet the protocol definition of RV dysfunction (CMR RV ejection fraction (EF) <45%) will be randomised to ranolazine or placebo with a ratio of 2:1. Enrolled subjects will be assessed for functional class, 6 min walk test and health outcome based on SF-36 tool. Peripheral blood will be obtained for N-terminal-pro brain natriuretic peptide, metabolic profiling, and microRNA at baseline and the conclusion of the treatment period. CMR will be performed at baseline and the conclusion of the treatment period. The primary outcome is change in RVEF. The exploratory outcomes include clinical, other CMR parameters, metabolic and microRNA changes.

Ethics and dissemination: The trial protocol was approved by Institutional Review Boards. The trial findings will be disseminated in scientific journals and meetings.

Trial registration numbers: NCT01839110 and NCT02829034; Pre-results.

Keywords: cardiac magnetic resonance imaging; pulmonary hypertension; ranolazine; right ventricle.

Conflict of interest statement

Competing interests: SYC reports consultancy agreements with Actelion, Gilead, Pfizer and Vivus. MHP reports consultant/scientific advisory, Actelion, Bayer, United Therapeutics and speakers’ bureau for Bayer.

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