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Carvedilol PAH A Pilot Study of Efficacy and Safety

Primary Purpose

Pulmonary Hypertension, Cardiac MRI <40

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carvedilol
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pulmonary Hypertension focused on measuring Hypertension, PAH

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subjects will be eligible to participate in the study if all of the following conditions exist:
  2. Age > 18 years
  3. WHO category 1 pulmonary arterial hypertension (Dana Point 2008)
  4. WHO functional class II-III
  5. RVEF by cardiac MRI < 40%
  6. Mean pulmonary artery pressure > 40 mm Hg
  7. 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:

  • 1. Subjects will be excluded from participation in the study if any of the following conditions exist: 2. Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker 3. Second or third degree AV block without a permanent pacemaker 4. Significant sinus tachycardia (resting heart rate > 100 bpm) 5. Use of anti-arrhythmic drugs 6. Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment 7. Significant illness in the past 30 days requiring hospitalization 8. Acute decompensated right heart failure within past 30 days 9. Known allergy or intolerance to carvedilol or other β blockers 10. Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg 11. Asthma

Sites / Locations

  • University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carvedilol

Arm Description

Carvedilol 0-3.125 mg daily Escalating to 6.25 twice a day

Outcomes

Primary Outcome Measures

Mean change in RVEF
1. The primary efficacy outcome is the mean change in RVEF as measured by cardiac MRI before and after 6 months of carvedilol treatment. An improvement of 5% will be considered to be clinically significant. Assessment of the RV is challenging due to its complex geometry. Cardiac MRI offers the ability to acquire 3-dimensional datasets that do not require geometric modeling. In addition to being highly reproducible40, RVEF measured by cardiac MRI can be used to identify PAH patients that are likely to have clinical worsening41. The prognostic ability of cardiac MRI-measurements of RVEF is similar to that as mean pulmonary artery pressure and exercise capacity

Secondary Outcome Measures

Absence of Adverse Events
The primary safety outcome is the absence of adverse events associated with carvedilol including hypotension (<90 mm Hg), bradycardia (<50 bpm or advanced atrioventricular nodal block), bronchospam, or acute decompensated right heart failure requiring hospitalization.

Full Information

First Posted
April 17, 2014
Last Updated
July 10, 2019
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT02120339
Brief Title
Carvedilol PAH A Pilot Study of Efficacy and Safety
Official Title
Beta Blockers in Pulmonary Arterial Hypertension (PAH) A Pilot Study of Efficacy and Safety
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
Low enrollment
Study Start Date
May 2014 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2016 (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
Estimate the effect of chronic beta-adrenergic receptor blockade with carvedilol on RV function in patients with PAH. Assess the safety and tolerability of chronic carvedilol therapy in patients with PAH
Detailed Description
This is a prospective, open label, uncontrolled, pilot study examining the safety and efficacy of beta-blocker therapy with carvedilol on RV function in stable PAH Patients with World Health Organization (WHO) functional class II or III symptoms and RV ejection fraction (EF) < 40%. Twenty-five evaluable patients will be enrolled at the University of Minnesota. Specific Aims: 1.1 Primary Efficacy Endpoint: Adult males and females on a stable dose of an approved PAH medication will undergo cardiac magnetic resonance imaging (MRI), right heart catheterization (RHC), echocardiogram, 6-minute walk test (6-MWT), measurement of plasma NT-ProBNP and serum catecholamine, and quality of life assessment. Patients will receive carvedilol (3.25 mg/kg bid escalating to 25 mg/kg bid over 3 months). Testing is repeated at the end of the study (month 6). RVEF measured by cardiac MRI is the primary efficacy endpoint. We define a 5% increase in RVEF as a meaningful change.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension, Cardiac MRI <40
Keywords
Hypertension, PAH

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol
Arm Type
Experimental
Arm Description
Carvedilol 0-3.125 mg daily Escalating to 6.25 twice a day
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Primary Outcome Measure Information:
Title
Mean change in RVEF
Description
1. The primary efficacy outcome is the mean change in RVEF as measured by cardiac MRI before and after 6 months of carvedilol treatment. An improvement of 5% will be considered to be clinically significant. Assessment of the RV is challenging due to its complex geometry. Cardiac MRI offers the ability to acquire 3-dimensional datasets that do not require geometric modeling. In addition to being highly reproducible40, RVEF measured by cardiac MRI can be used to identify PAH patients that are likely to have clinical worsening41. The prognostic ability of cardiac MRI-measurements of RVEF is similar to that as mean pulmonary artery pressure and exercise capacity
Time Frame
Baseline and 6 months
Secondary Outcome Measure Information:
Title
Absence of Adverse Events
Description
The primary safety outcome is the absence of adverse events associated with carvedilol including hypotension (<90 mm Hg), bradycardia (<50 bpm or advanced atrioventricular nodal block), bronchospam, or acute decompensated right heart failure requiring hospitalization.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects will be eligible to participate in the study if all of the following conditions exist: Age > 18 years WHO category 1 pulmonary arterial hypertension (Dana Point 2008) WHO functional class II-III RVEF by cardiac MRI < 40% Mean pulmonary artery pressure > 40 mm Hg 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: 1. Subjects will be excluded from participation in the study if any of the following conditions exist: 2. Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker 3. Second or third degree AV block without a permanent pacemaker 4. Significant sinus tachycardia (resting heart rate > 100 bpm) 5. Use of anti-arrhythmic drugs 6. Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment 7. Significant illness in the past 30 days requiring hospitalization 8. Acute decompensated right heart failure within past 30 days 9. Known allergy or intolerance to carvedilol or other β blockers 10. Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg 11. Asthma
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
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34259020
Citation
Thenappan T, Weir EK, Prins KW, Pritzker MR, Archer SL. Carvedilol for Treatment of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2021 Jul 20;10(14):e021518. doi: 10.1161/JAHA.121.021518. Epub 2021 Jul 14. No abstract available.
Results Reference
derived

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Carvedilol PAH A Pilot Study of Efficacy and Safety

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