# REHAB-PH Trial: Repurposing a Histamine Antagonist to Benefit Patients with Pulmonary Hypertension

> **NIH NIH R33** · UNIVERSITY OF WASHINGTON · 2020 · $708,040

## Abstract

Although there has been substantial progress in the development of medications to lower pulmonary
vascular resistance in pulmonary arterial hypertension (PAH), there are no therapies that are known to
benefit the right heart in the absence of changes in right ventricular afterload. Right heart failure is the
key driver for morbidity and mortality in patients with PAH, but also complicates a range of other
common diseases such as emphysema and left heart failure.
We are pursuing a novel approach that targets histamine H2 receptors in patients with PAH and right
heart failure. Previous animal studies suggest myocardial H2 receptors contribute to myocardial fibrosis
and are important heart failure mediators. A previous randomized controlled trial showed famotidine
improved b-natriuretic peptide, left ventricular morphology, and symptoms in participants with Heart
Failure and Reduced Ejection Fraction (left heart failure). Our work has shown differences in right
ventricular morphology among community dwelling adults and a lower all-cause mortality in veterans
with pulmonary hypertension who use H2 receptor antagonists. These preliminary results raise the
strong possibility that H2 receptor antagonism might be an effective treatment for right heart failure.
H2 receptor antagonism is an appealing therapeutic target that is well aligned with current NIH priorities
of repurposing existing, inexpensive, and well-tolerated medications for novel use in other disease
states. Medications for pulmonary arterial hypertension are particularly expensive. If adjunctive therapy
with an H2 receptor antagonist is efficacious this would benefit PAH patients and society at-large.
We propose a Phase 2, single-center, randomized placebo controlled trial of famotidine (an H2 receptor
antagonist) in adults with PAH. The study will evaluate the safety and clinical efficacy of a 24-week
course of famotidine. The primary end-point is six-minute walk distance at 24 weeks. Secondary
endpoints include differences in right ventricular function, biochemical markers of right heart failure (nt-
pro-BNP), New York Heart Association Functional Class, health related quality of life as assessed by
the disease specific emPHasis-10 instrument, and the frequency with which routine therapies for
patients with PAH are escalated during the trial.

## Key facts

- **NIH application ID:** 10022303
- **Project number:** 5R33HL142539-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Peter J Leary
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $708,040
- **Award type:** 5
- **Project period:** 2018-09-16 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022303

## Citation

> US National Institutes of Health, RePORTER application 10022303, REHAB-PH Trial: Repurposing a Histamine Antagonist to Benefit Patients with Pulmonary Hypertension (5R33HL142539-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022303. Licensed CC0.

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