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  • 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

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Pulmonary vascular disease
Protocol
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
  1. Yuchi Han1,
  2. Paul R Forfia2,
  3. Anjali Vaidya2,
  4. Jeremy A Mazurek1,
  5. Myung H Park3,
  6. Gautam Ramani4,
  7. Stephen Y Chan5 and
  8. Aaron B Waxman6
  1. 1Cardiovascular Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  2. 2Cardiovascular Division, Temple University, Philadelphia, Pennsylvania, USA
  3. 3Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, USA
  4. 4Cardiovascular Division, University of Maryland, Baltimore, Maryland, USA
  5. 5Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  6. 6Center for Pulmonary Heart Disease, Heart and Vascular and Lung Centers, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Yuchi Han; yuchi.han{at}uphs.upenn.edu

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.

  • pulmonary hypertension
  • right ventricle
  • cardiac magnetic resonance imaging
  • ranolazine

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2017-000736

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    Footnotes

    • Contributors YH, MHP, SYC, PF and ABW were involved in the initial drafting of the protocol. AV, JAM and GR contributed to refinement of the protocol. All authors read and approved the protocol.

    • Funding This work was supported by Cardiovascular Medical Research and Education Fund (CMREF), Philadelphia, PA, to YH and an investigator-initiated grant funded by Gilead Sciences to YH. The study is also supported in part by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878. ABW was supported by U01 HL125215, R01 HL131910 and R42 HL132742. SYC was supported by NIH grants R01 HL124021, HL 122596, HL 138437 and UH2 TR002073.

    • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

    • 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.

    • Patient consent Obtained.

    • Ethics approval Institutional Review Board of University of Pennsylvania, University of Maryland and Brigham Women’s Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement The full data set is available from the corresponding author upon reasonable request.