Carvedilol PAH A Pilot Study of Efficacy and Safety

Phase 1

Terminated

• Conditions: Pulmonary Hypertension; Cardiac MRI <40
• Interventions: Drug: Carvedilol

• Registration Number: NCT02120339
• Lead Sponsor: University of Minnesota

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-04-17
• Study First Submitted QC: 2014-04-17
• Study First Posted: 2014-04-22
• Study Start: 2014-05
• Primary Completion: 2015-06
• Study Completion: 2016-06
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-10
• Last Update Posted: 2019-07-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Mean change in RVEF	Baseline and 6 months	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

Name	Time	Method
Absence of Adverse Events	6 months	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.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States