Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension (REHAB-PH)

This is a Phase 2, single-center, randomized placebo controlled trial of famotidine (an H2 receptor antagonist) in adults with pulmonary arterial hypertension. The study will evaluate the safety and clinical efficacy of a 24-week course of famotidine.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension; Right Heart Failure
• Intervention / Treatment: Drug: Famotidine 20 MG; Other: Placebo

Detailed Description

Pulmonary arterial hypertension (PAH) is one of many conditions that put stress and strain on the right side of the heart. This stress and strain can cause right heart failure. Although there are medications to treat PAH, there are currently no medications that act directly on the heart to improve right heart function. This is different than left heart failure where one of the cornerstones of treatment is medication targeted at the heart to improve left heart function.

Famotidine is a well-tolerated, over-the-counter, and inexpensive medication. Preliminary results suggest that famotidine may help the right heart to adapt and strengthen when stressed instead of fail; however, these results are suggestive and not definitive. A randomized controlled trial is required to evaluate the possibility that famotidine can impact right heart function.

Participants in the study will take famotidine or placebo for 24 weeks. They will have three study visits at 0, 12, and 24 weeks. These visits will add 20-30 minutes to the standard clinic visits at those time points and there will be an echocardiogram at weeks 0 and 24. There will also be one phone visit at 4 weeks to check-in. Some participants may elect to participate in exercise testing and/or right heart catheterization at weeks 0 and 24; however, this is not required to participate in the trial.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laurie Hogl; Phone Number: 206-543-8334; Email: lalnaser@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, age 18 to 80
• WHO Group 1 Pulmonary Arterial Hypertension
• NYHA Functional Class II, III, or IV at screening
• Stable dose of pulmonary vasodilators for 30 days prior to randomization
• Right heart catheterization within five years demonstrating a mean pulmonary arterial pressure of ≥ 25 mmHg, occlusion pressure of ≤ 15 mmHg, and pulmonary vascular resistance of ≥ 3 wood units
• Participants with a right heart catheterization within five years demonstrating a mean pulmonary arterial pressure of ≥ 25 mmHg and occlusion pressure of 15 - 20 mmHg will be considered for inclusion if the pulmonary vascular resistance ≥ 9 wood units and they are being treated with pulmonary arterial hypertension specific therapy
• Able to walk with/without a walking aid for a distance of at least 50 meters

Exclusion Criteria:

• Pregnant or lactating
• Non-group 1 pulmonary hypertension or veno-occlusive disease
• History of interstitial lung disease, unless subject has collagen vascular disease and has pulmonary function testing conducted within 12 months demonstrating a total lung capacity of ≥ 60 %
• Has received or will receive an investigational drug, device, or study within 30 days or during the course of study
• Left sided myocardial disease as evidenced by left ventricular ejection fraction < 40%
• Any other clinically significant illness or abnormal laboratory values (measured during the Screening period) that, in the opinion of the Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data
• Anticipated survival less than 1 year due to concomitant disease
• Regularly taking an H2 receptor antagonist within 30 days of enrollment
• Creatinine clearance < 30 mL/min
• History of bariatric surgery
• Current treatment for HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Famotidine; 20mg of oral famotidine (pill) daily Other names: Pepcid	Drug: Famotidine 20 MG; Famotidine 20 mg capsule taken daily for 24 weeks.
Placebo Comparator: Placebo; Daily oral placebo (pill)	Other: Placebo; Placebo capsule taken daily for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six-minute walk distance	To determine whether famotidine increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension	0 to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BNP	To determine whether famotidine reduces BNP at 24 weeks	0 to 24 weeks
New York Heart Association (NYHA) functional class	To determine whether famotidine improves New York Heart Association (NYHA) functional class at 24 weeks	0 to 24 weeks
Right ventricular morphology by echocardiogram (RV dilation and TAPSE)	To determine whether famotidine improves right ventricular morphology at 24 weeks including improved right ventricular dilation and TAPSE	0 to 24 weeks
Health related quality of life (emPHasis-10 questionnaire)	To determine whether famotidine improves health related quality of life as estimated by the emPHasis-10 score (Each item on the emPHasis-10 questionnaire is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end; EmPHasis-10 scores range from 0 to 50 with higher scores indicating worse quality of life).	0 to 24 weeks
Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators)	To determine whether famotidine decreases the need to escalate PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding an additional pulmonary vasodilator)	0 to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive hemodynamics (sub-study): Stroke Volume Index	To determine whether famotidine increases stroke volume index at 24 weeks	0 to 24 weeks
Cardiopulmonary Exercise Testing (sub-study): Maximal oxygen uptake	To determine whether famotidine increases maximal oxygen uptake in individuals with pulmonary arterial hypertension at 24 weeks	0 to 24 weeks
Invasive hemodynamics (sub-study): Hemodynamics	Exploratory: To explore whether famotidine improves hemodynamics (wedge, RA, PVR) at 24 weeks	0 to 24 weeks
Cardiopulmonary Exercise Testing (sub-study): Exercise	Exploratory: To explore whether famotidine improves exercise (Ve/VCO2 ratio, total achieved wattage).	0 to 24 weeks

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Peter J Leary, MD, PhD, University of Washington

Publications and helpful links

General Publications

• Leary PJ, Barr RG, Bluemke DA, Bristow MR, Kronmal RA, Lima JA, Ralph DD, Ventetuolo CE, Kawut SM. H2 receptor antagonists and right ventricular morphology: the MESA right ventricle study. Ann Am Thorac Soc. 2014 Nov;11(9):1379-86. doi: 10.1513/AnnalsATS.201407-344OC.
• Leary PJ, Tedford RJ, Bluemke DA, Bristow MR, Heckbert SR, Kawut SM, Krieger EV, Lima JA, Masri CS, Ralph DD, Shea S, Weiss NS, Kronmal RA. Histamine H2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk: The MESA Study. J Am Coll Cardiol. 2016 Apr 5;67(13):1544-1552. doi: 10.1016/j.jacc.2016.01.045.
• Leary PJ, Kronmal RA, Bluemke DA, Buttrick PM, Jones KL, Kao DP, Kawut SM, Krieger EV, Lima JA, Minobe W, Ralph DD, Tedford RJ, Weiss NS, Bristow MR. Histamine H2 Receptor Polymorphisms, Myocardial Transcripts, and Heart Failure (from the Multi-Ethnic Study of Atherosclerosis and Beta-Blocker Effect on Remodeling and Gene Expression Trial). Am J Cardiol. 2018 Jan 15;121(2):256-261. doi: 10.1016/j.amjcard.2017.10.016. Epub 2017 Oct 20.
• Leary PJ, Hess E, Baron AE, Branch KR, Choudhary G, Hough CL, Maron BA, Ralph DD, Ryan JJ, Tedford RJ, Weiss NS, Zamanian RT, Lahm T. H2 Receptor Antagonist Use and Mortality in Pulmonary Hypertension: Insight from the VA-CART Program. Am J Respir Crit Care Med. 2018 Jun 15;197(12):1638-1641. doi: 10.1164/rccm.201801-0048LE. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): July 11, 2023
• Study Completion (Actual): July 11, 2023

Study Registration Dates

• First Submitted: May 31, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: famotidine; H2 blocker; H2 antagonist
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Famotidine
• Other Study ID Numbers: STUDY00005002; 1R61HL142539-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes