Beta-blockers in Pulmonary Arterial Hypertension

Beta-blockers in Pulmonary Arterial Hypertension - A Phase 2 Double-Blind, Placebo-Controlled, Crossover Study Evaluating the Efficacy, and Safety of Carvedilol for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Carvedilol

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).

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carvedilol First; Crossover Design: Participants receive Carvedilol first and placebo second	Drug: Placebo; Placebo; Drug: Carvedilol; Beta-adrenergic receptor blocker; Other Names: Beta-blockers
Placebo Comparator: Placebo First; Crossover Design: Participants receive placebo first and Carvedilol second	Drug: Placebo; Placebo; Drug: Carvedilol; Beta-adrenergic receptor blocker; Other Names: Beta-blockers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI	6 months

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Thenappan Thenappan, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2016
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: 1504M69361

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO