Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

NCT03554291 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY000050021R61HL142539-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension; Right Heart Failure

Keywords

famotidine; H2 blocker; H2 antagonist

Outcome Measures

Primary Outcomes (1)

• Change in 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 Outcomes (5)

• Chang in Log-transformed BNP

  0 to 24 weeks

• Proportion of Participants With New York Heart Association (NYHA) Functional Class of I or II at Week 24

  24 weeks

• Change in Right Ventricular Morphology by Echocardiogram (RV Dilation and TAPSE)

  0 to 24 weeks

• Change in Health Related Quality of Life (emPHasis-10 Questionnaire)

  0 to 24 weeks

• Percent of Participants by Arm Who Added PAH Focused Care (Increased Diuretics, Escalating Doses of Pulmonary Vasodilators, and/or Adding Additional Pulmonary Vasodilators) Over 24 Weeks.

  0 to 24 weeks

Other Outcomes (4)

• Invasive Hemodynamics (Sub-study): Stroke Volume Index

  0 to 24 weeks

• Cardiopulmonary Exercise Testing (Sub-study): Maximal Oxygen Uptake

  0 to 24 weeks

• Invasive Hemodynamics (Sub-study): Hemodynamics

  0 to 24 weeks

Study Arms (2)

Famotidine

EXPERIMENTAL

20mg of oral famotidine (pill) daily Other names: Pepcid

Drug: Famotidine 20 MG

Placebo

PLACEBO COMPARATOR

Daily oral placebo (pill)

Other: Placebo

Interventions

Famotidine 20 MG DRUG

Famotidine 20 mg capsule taken daily for 24 weeks.

Famotidine

Placebo OTHER

Placebo capsule taken daily for 24 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Able to walk with/without a walking aid for a distance of at least 50 meters

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (5)

• 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.

  PMID: 25295642 BACKGROUND

• 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.

  PMID: 27150686 BACKGROUND

• 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.

  PMID: 29191567 BACKGROUND

• 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.

  PMID: 29437490 BACKGROUND

• Leary PJ, Rayner SG, Branch KRH, Hogl L, Liston NM, Barros LM, Prout J, Nolley S, Buber J, Ralph DD, Probstfield JL. Effect of Famotidine on Outcomes in Pulmonary Arterial Hypertension: A Randomized Controlled Trial. Chest. 2025 Jul;168(1):189-199. doi: 10.1016/j.chest.2024.12.029. Epub 2025 Jan 4.

  PMID: 39761829 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Heart Failure

Interventions

Famotidine

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Peter Leary
• Organization: University of Washington

learyp@uw.edu

206-685-2484

Study Officials

• Peter J Leary, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pulmonary Vascular Disease Program

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: June 13, 2018
• Study Start: May 1, 2019
• Primary Completion: July 11, 2023
• Study Completion: July 11, 2023
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)