Pulmonary Arterial HypertensionPhase 2REHAB-PHNCT03554291
Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension
A Phase 2 study testing Famotidine 20 MG in people with Pulmonary Arterial Hypertension and Right Heart Failure, run by University of Washington at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pulmonary Arterial Hypertension, Right Heart Failure
- What is being tested?
- Famotidine 20 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to 11 Jul 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Washington Medical Center
Seattle, Washington, 98195
About this study
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.
Read the 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.
- Being tested
- Famotidine 20 MG, Placebo
- Keywords
- famotidine, H2 blocker, H2 antagonist
- Medical subject headings
- Pulmonary Arterial Hypertension, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Famotidine 20 MGDrug
Famotidine 20 mg capsule taken daily for 24 weeks.
PlaceboOther
Placebo capsule taken daily for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Famotidine | Experimental | 20mg of oral famotidine (pill) daily
Other names: Pepcid Receives: Drug: Famotidine 20 MG |
| Placebo | Placebo comparator | Daily oral placebo (pill) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 0 to 24 weeks
Secondary outcomes (5)
Chang in Log-transformed BNP
To determine whether famotidine reduces log-transformed BNP at 24 weeks
Measured: 0 to 24 weeks
Proportion of Participants With New York Heart Association (NYHA) Functional Class of I or II at Week 24
NYHA functional class is graded from 1 to 4 (1: no symptoms of heart failure; 2: symptoms of heart failure with moderate exertion; 3: symptoms of heart failure with mild exertion; 4: symptoms of heart failure at rest). As such, NYHA functional class 1 is considered better than NYHA functional class 4.
Measured: 24 weeks
Change in 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
Measured: 0 to 24 weeks
Change in 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).
Measured: 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.
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). The confidence interval includes a negative percent (e.g. a participant who de-escalated care).
Measured: 0 to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2018
- Study start1 May 2019
- Primary completion11 Jul 2023
- Study completion11 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Peter Leary, University of Washington
- Investigators
- Peter J Leary, MD, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03554291
- Sponsor's protocol ID
- STUDY00005002
- Other IDs
- 1R61HL142539-01
- Acronym
- REHAB-PH
- Status last verified
- Aug 2024
- First submitted
- 31 May 2018
- Last updated
- 9 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 25295642Leary 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.
PubMed 27150686Leary 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.
PubMed 29191567Leary 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.
PubMed 29437490Leary 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.
PubMed 39761829
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT03554291
- Acronym / sponsor ID
- REHAB-PH / STUDY00005002
- Keywords
- famotidine, H2 blocker, H2 antagonist
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 May 2019 (actual)
- Primary completion
- 11 Jul 2023 (actual)
- Study completion
- 11 Jul 2023 (actual)
- First posted
- 13 Jun 2018 (actual)
- Results
- Posted 9 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Famotidine | Experimental | Drug: Famotidine 20 MG20mg of oral famotidine (pill) daily Other names: Pepcid |
| Placebo | Placebo comparator | Other: PlaceboDaily oral placebo (pill) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Famotidine 20 MGFamotidine 20 mg capsule taken daily for 24 weeks. | Drug | Famotidine |
| PlaceboPlacebo capsule taken daily for 24 weeks. | Other | Placebo |
Primary outcome
Change in Six-minute Walk Distance
Time frame: 0 to 24 weeks
To determine whether famotidine increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension
5 secondary outcomes
Chang in Log-transformed BNP
Time frame: 0 to 24 weeks
Proportion of Participants With New York Heart Association (NYHA) Functional Class of I or II at Week 24
Time frame: 24 weeks
Change in Right Ventricular Morphology by Echocardiogram (RV Dilation and TAPSE)
Time frame: 0 to 24 weeks
Change in Health Related Quality of Life (emPHasis-10 Questionnaire)
Time frame: 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.
Time frame: 0 to 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25295642Leary 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.
- Background: PubMed 27150686Leary 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.
- Background: PubMed 29191567Leary 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.
- Background: PubMed 29437490Leary 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.
- Derived from this study: PubMed 39761829Leary 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter J Leary, MD, PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Famotidine 20 MG in people with Pulmonary Arterial Hypertension and Right Heart Failure, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Six-minute Walk Distance (time frame: 0 to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03554291, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.