Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Study Overview
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Brief Summary
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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
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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.

Official Title
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Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Conditions
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Pulmonary Arterial Hypertension, Right Heart Failure

Intervention / Treatment
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* Drug: Famotidine 20 MG
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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famotidine, H2 blocker, H2 antagonist