Carvedilol PAH A Pilot Study of Efficacy and Safety

NCT ID: NCT02120339

Last Updated: 2019-07-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-06-30

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.

Conditions

Pulmonary Hypertension; Cardiac MRI <40

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Carvedilol

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

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

Interventions

Carvedilol

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 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

Minneapolis, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34259020 (View on PubMed)

Other Identifiers

PAH

Identifier Type: -

Identifier Source: org_study_id