Trial Outcomes & Findings for Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension (NCT NCT03554291)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

0 to 24 weeks

Results posted on

2024-08-09

Participant Flow

Participant milestones

Participant milestones
Measure	Famotidine 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Overall Study STARTED	41	39
Overall Study COMPLETED	34	38
Overall Study NOT COMPLETED	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Famotidine 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Overall Study Death	2	1
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study COVID Travel Restriction- Partial Data Collected	3	0

Baseline Characteristics

Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.	Total n=79 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 13.7 • n=5 Participants	51.4 years STANDARD_DEVIATION 12.7 • n=7 Participants	50.6 years STANDARD_DEVIATION 13.2 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	31 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	35 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Six-minute walk distance	414 meters STANDARD_DEVIATION 91 • n=5 Participants	407 meters STANDARD_DEVIATION 107 • n=7 Participants	411 meters STANDARD_DEVIATION 99 • n=5 Participants

PRIMARY outcome

Timeframe: 0 to 24 weeks

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

Outcome measures

Outcome measures
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Change in Six-minute Walk Distance	-17.0 meters Interval -43.6 to 9.7	4.7 meters Interval -20.1 to 29.6

SECONDARY outcome

Timeframe: 0 to 24 weeks

To determine whether famotidine reduces log-transformed BNP at 24 weeks

Outcome measures

Outcome measures
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Chang in Log-transformed BNP	-0.05 Log of pg/mL Interval -0.16 to 0.26	0.08 Log of pg/mL Interval -0.12 to 0.27

SECONDARY outcome

Timeframe: 24 weeks

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.

Outcome measures

Outcome measures
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Proportion of Participants With New York Heart Association (NYHA) Functional Class of I or II at Week 24	0.71 Proportion participants NYHA class I/II Interval 0.54 to 0.85	0.53 Proportion participants NYHA class I/II Interval 0.36 to 0.69

SECONDARY outcome

Timeframe: 0 to 24 weeks

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

Outcome measures

Outcome measures
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Change in Right Ventricular Morphology by Echocardiogram (RV Dilation and TAPSE) RV dilation	-1.5 RV basal diameter (cm)/TAPSE (mm) Interval -3.2 to 0.3	0.9 RV basal diameter (cm)/TAPSE (mm) Interval -0.9 to 2.6
Change in Right Ventricular Morphology by Echocardiogram (RV Dilation and TAPSE) TAPSE	0.1 RV basal diameter (cm)/TAPSE (mm) Interval -1.2 to 1.3	0.7 RV basal diameter (cm)/TAPSE (mm) Interval -0.6 to 1.9

SECONDARY outcome

Timeframe: 0 to 24 weeks

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).

Outcome measures

Outcome measures
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Change in Health Related Quality of Life (emPHasis-10 Questionnaire)	-1.7 score on a scale Interval -4.2 to 0.8	-1.3 score on a scale Interval -3.9 to 1.2

SECONDARY outcome

Timeframe: 0 to 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).

Outcome measures

Outcome measures
Measure	Famotidine n=40 Participants 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 Participants Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 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.	8.1 model-based percentage of participants Interval -0.3 to 18.9	5.3 model-based percentage of participants Interval -1.8 to 12.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 24 weeks

Other events: 14 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Famotidine n=40 participants at risk 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 participants at risk Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Infections and infestations Coronavirus, Medical Device Site Infection, Metapneumovirus, Pneumonia	10.0% 4/40 • Number of events 4 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	5.1% 2/39 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Cardiac disorders Atrial flutter, Angina Pectoris, Cardiac Failure	10.0% 4/40 • Number of events 4 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Nervous system disorders syncope, encephalopathy	7.5% 3/40 • Number of events 3 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Metabolism and nutrition disorders Dehydration, Hypokalemia	5.0% 2/40 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Renal and urinary disorders Acute Kidney Injury	5.0% 2/40 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Respiratory, thoracic and mediastinal disorders Dyspnea, Hemoptysis	5.0% 2/40 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Product Issues Device malfunction	0.00% 0/40 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Vascular disorders Hypotension	2.5% 1/40 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.

Other adverse events

Other adverse events
Measure	Famotidine n=40 participants at risk 20mg of oral famotidine (pill) daily Other names: Pepcid Famotidine 20 MG: Famotidine 20 mg capsule taken daily for 24 weeks.	Placebo n=39 participants at risk Daily oral placebo (pill) Placebo: Placebo capsule taken daily for 24 weeks.
Gastrointestinal disorders Abdominal pain, dyspepsia, nausea, flatulence, discomfort	20.0% 8/40 • Number of events 8 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	12.8% 5/39 • Number of events 5 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Infections and infestations Coronavirus, Influenza, Medical Device site infection, Ear infection, Metapneumovirus, Nasopharyngit	20.0% 8/40 • Number of events 8 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	10.3% 4/39 • Number of events 4 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Nervous system disorders Syncope, Dizziness, Headache, Dysgeusia, Encephalopathy	12.5% 5/40 • Number of events 5 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
General disorders non-cardiac chest pain, swelling	5.0% 2/40 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Respiratory, thoracic and mediastinal disorders dyspnea, hemoptysis, throat irritation	10.0% 4/40 • Number of events 4 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Cardiac disorders angina, atrial flutter, cardiac failure	10.0% 4/40 • Number of events 4 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Metabolism and nutrition disorders dehydration, hypokalemia	5.0% 2/40 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Renal and urinary disorders acute kidney injury,	5.0% 2/40 • Number of events 2 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Musculoskeletal and connective tissue disorders back pain, bursitis, neck pain	2.5% 1/40 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Skin and subcutaneous tissue disorders rash	2.5% 1/40 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Injury, poisoning and procedural complications ligament strain, muscle strain	0.00% 0/40 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Product Issues device malfunction	0.00% 0/40 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	2.6% 1/39 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Reproductive system and breast disorders vaginal hemorrhage	2.5% 1/40 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.
Vascular disorders hypotension	2.5% 1/40 • Number of events 1 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.	0.00% 0/39 • Adverse events were collected over 24 weeks. Events were collected during all study visits and on a continuous basis as reported by participants or their proxies.

Additional Information

Peter Leary

University of Washington

Phone: 206-685-2484

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place