Beta-blockers in Pulmonary Arterial Hypertension

NCT ID: NCT02507011

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2019-07-01

Brief Summary

The investigators will conduct a, randomized, phase 2, placebo-controlled, double-blinded, crossover trial of carvedilol in 26 PAH patients with World Health Organization functional class II or III symptoms and RV ejection fraction (EF) < 45% for 6 months.

Detailed Description

Adult PAH patients on a stable dose of an approved PAH medication will undergo the following baseline assessments: cardiac magnetic resonance imaging (MRI), right heart catheterization (RHC), echocardiogram, 6-minute walk test (6-MWT), plasma NT-ProBNP (biomarkers of RV function) and serum catecholamine (measure of sympathetic activation), and quality of life. Patients will be randomized to carvedilol (3.125 mg bid and escalated to 9.375 mg bid, as tolerated, over 3 months) or placebo in a 1:1 fashion. After 6 months, testing is repeated and patients are crossed over to the alternate treatment. Testing is repeated at the end of the study (month 13).

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Carvedilol First

Crossover Design: Participants receive Carvedilol first and placebo second

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

Beta-adrenergic receptor blocker

Placebo

Intervention Type: DRUG

Placebo

Placebo First

Crossover Design: Participants receive placebo first and Carvedilol second

Group Type: PLACEBO_COMPARATOR

Carvedilol

Intervention Type: DRUG

Beta-adrenergic receptor blocker

Placebo

Intervention Type: DRUG

Placebo

Interventions

Carvedilol

Beta-adrenergic receptor blocker

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Beta-blockers

Eligibility Criteria

Inclusion Criteria

• Age > 18 years
• WHO category 1 pulmonary arterial hypertension (Nice 2013)
• WHO functional class II-III
• RVEF by cardiac MRI < 45%
• Stable on PAH-specific therapy as defined by no change in PAH-specific treatment and functional class in the past 3 months. Patient can be on either mono or combination PAH-specific therapy

Exclusion Criteria

• Subjects will be excluded from participation in the study if any of the following conditions exist:
• Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker
• Second or third degree AV block without a permanent pacemaker
• Significant sinus tachycardia (resting heart rate > 110 bpm)
• Use of anti-arrhythmic drugs
• Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment
• Significant illness in the past 30 days requiring hospitalization
• Acute decompensated right heart failure within past 30 days
• Known allergy or intolerance to carvedilol or other β blockers
• Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg by right heart catheterization within last 3 months
• Asthma
• Positive pregnancy test in patients of child bearing-potential

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thenappan Thenappan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1504M69361

Identifier Type: -

Identifier Source: org_study_id