Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— REHAB-PH  

Official title:

Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03554291
• Other study ID #: STUDY00005002
• Secondary ID: 1R61HL142539-01
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2019
• Est. completion date: July 11, 2023

Study information

• Verified date: July 2023
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: July 11, 2023
• Est. primary completion date: July 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension
• Right Heart Failure

Intervention

Drug:
• Famotidine 20 MG
Famotidine 20 mg capsule taken daily for 24 weeks.

Other:
• Placebo
Placebo capsule taken daily for 24 weeks.

Locations

Country	Name	City	State
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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 Ca — View 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 Stu — View 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 C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Invasive hemodynamics (sub-study): Stroke Volume Index	To determine whether famotidine increases stroke volume index at 24 weeks	0 to 24 weeks
Other	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
Other	Invasive hemodynamics (sub-study): Hemodynamics	Exploratory: To explore whether famotidine improves hemodynamics (wedge, RA, PVR) at 24 weeks	0 to 24 weeks
Other	Cardiopulmonary Exercise Testing (sub-study): Exercise	Exploratory: To explore whether famotidine improves exercise (Ve/VCO2 ratio, total achieved wattage).	0 to 24 weeks
Primary	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	BNP	To determine whether famotidine reduces BNP at 24 weeks	0 to 24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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