Beta-blockers in Pulmonary Arterial Hypertension
Primary Purpose
Pulmonary Arterial Hypertension
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carvedilol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
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
Sites / Locations
- University of Minnesota Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Carvedilol First
Placebo First
Arm Description
Crossover Design: Participants receive Carvedilol first and placebo second
Crossover Design: Participants receive placebo first and Carvedilol second
Outcomes
Primary Outcome Measures
Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02507011
Brief Title
Beta-blockers in Pulmonary Arterial Hypertension
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
Recruitment
Study Start Date
January 31, 2016 (Actual)
Primary Completion Date
July 1, 2019 (Actual)
Study Completion Date
July 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carvedilol First
Arm Type
Experimental
Arm Description
Crossover Design: Participants receive Carvedilol first and placebo second
Arm Title
Placebo First
Arm Type
Placebo Comparator
Arm Description
Crossover Design: Participants receive placebo first and Carvedilol second
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Other Intervention Name(s)
Beta-blockers
Intervention Description
Beta-adrenergic receptor blocker
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thenappan Thenappan, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Beta-blockers in Pulmonary Arterial Hypertension
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