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

Primary Purpose

Pulmonary Arterial Hypertension, Right Heart Failure

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Famotidine 20 MG

Placebo

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring famotidine, H2 blocker, H2 antagonist

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Washington Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Famotidine

Placebo

Arm Description

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

Daily oral placebo (pill)

Outcomes

Primary Outcome Measures

Six-minute walk distance

To determine whether famotidine increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension

Secondary Outcome Measures

BNP

To determine whether famotidine reduces BNP at 24 weeks

New York Heart Association (NYHA) functional class

To determine whether famotidine improves New York Heart Association (NYHA) functional class at 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

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).

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)

Full Information

NCT ID

NCT03554291

First Posted

May 31, 2018

Last Updated

July 13, 2023

Sponsor

University of Washington

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT03554291

Brief Title

Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Acronym

REHAB-PH

Official Title

Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

May 1, 2019 (Actual)

Primary Completion Date

July 11, 2023 (Actual)

Study Completion Date

July 11, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Washington

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial Hypertension, Right Heart Failure

Keywords

famotidine, H2 blocker, H2 antagonist

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Famotidine

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Daily oral placebo (pill)

Intervention Type

Drug

Intervention Name(s)

Famotidine 20 MG

Intervention Description

Famotidine 20 mg capsule taken daily for 24 weeks.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo capsule taken daily for 24 weeks.

Primary Outcome Measure Information:

Title

Six-minute walk distance

Description

To determine whether famotidine increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension

Time Frame

0 to 24 weeks

Secondary Outcome Measure Information:

Title

BNP

Description

To determine whether famotidine reduces BNP at 24 weeks

Time Frame

0 to 24 weeks

Title

New York Heart Association (NYHA) functional class

Description

To determine whether famotidine improves New York Heart Association (NYHA) functional class at 24 weeks

Time Frame

0 to 24 weeks

Title

Right ventricular morphology by echocardiogram (RV dilation and TAPSE)

Description

To determine whether famotidine improves right ventricular morphology at 24 weeks including improved right ventricular dilation and TAPSE

Time Frame

0 to 24 weeks

Title

Health related quality of life (emPHasis-10 questionnaire)

Description

Time Frame

0 to 24 weeks

Title

Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators)

Description

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)

Time Frame

0 to 24 weeks

Other Pre-specified Outcome Measures:

Title

Invasive hemodynamics (sub-study): Stroke Volume Index

Description

To determine whether famotidine increases stroke volume index at 24 weeks

Time Frame

0 to 24 weeks

Title

Cardiopulmonary Exercise Testing (sub-study): Maximal oxygen uptake

Description

To determine whether famotidine increases maximal oxygen uptake in individuals with pulmonary arterial hypertension at 24 weeks

Time Frame

0 to 24 weeks

Title

Invasive hemodynamics (sub-study): Hemodynamics

Description

Exploratory: To explore whether famotidine improves hemodynamics (wedge, RA, PVR) at 24 weeks

Time Frame

0 to 24 weeks

Title

Cardiopulmonary Exercise Testing (sub-study): Exercise

Description

Exploratory: To explore whether famotidine improves exercise (Ve/VCO2 ratio, total achieved wattage).

Time Frame

0 to 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peter J Leary, MD, PhD

Organizational Affiliation

University of Washington

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Washington Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25295642

Citation

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.

Results Reference

result

PubMed Identifier

27150686

Citation

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.

Results Reference

result

PubMed Identifier

29191567

Citation

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.

Results Reference

result

PubMed Identifier

29437490

Citation

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.

Results Reference

result

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Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

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