Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension

The purpose of this study is to determine whether carvedilol treatment of patients with pulmonary arterial hypertension and associated right heart failure is safe and results in an improved function of the right heart.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Carvedilol

Detailed Description

Patients with pulmonary arterial hypertension (PAH) will be treated with carvedilol for 24 weeks. During this time, carvedilol will be titrated from an initial dose of 3.125mg BID to a maximal dose of 25mg BID. At the start and end of the study, we will obtain cardiac MRI, 6 minute walk distance, brain natriuretic peptide (serum), echocardiogram, and functional class assessment. Our primary outcome is a change in right ventricular ejection fraction with cardiac MRI.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

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:

• idiopathic, familial or associated PAH, WHO group 1
• NYHA class II or III
• clinically stable with optimized PAH treatment for at least 3 months
• no or minimal evidence of fluid overload or volume depletion, with or without diuretic treatment
• age > 18 years
• mean pulmonary artery pressure (mPAP) > 25 mmHg
• 6 minute walk distance (6MWD) over 100m

Exclusion Criteria:

• Structural heart disease unrelated to PAH
• Recent (<3 months) treatment with an intravenous positive inotropic agent
• current use of β-blockers
• history of reactive airways disease
• history of adverse reaction to β-blockers
• heart block on ECG or resting heart rate < 60 bpm
• cardiac index < 1.8 l/min/m2
• systemic hypotension (systolic pressure < 90 mmHg)
• pulmonary capillary wedge pressure > 15 mmHg
• inability to give informed consent
• contraindications to CT and/or PET scanning
• coagulopathy (INR>1.5 or platelet count<50000/mm3)
• severe renal insufficiency (creatinine clearance <30 ml/min/m2)
• malignancy or any co-morbidity limiting survival or conditions predicting inability to complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: carvedilol; Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI	Drug: Carvedilol; twice daily oral treatment in escalating dose; Other Names: Coreg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Right Ventricular Ejection Fraction	Change in right ventricular ejection fraction is measured by cardiac magnetic resonance imaging, using the method of disks with the reading radiologist being blinded to before and after images. Cardiac magnetic resonance imaging was done at baseline and 6 months only	baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Right Ventricular End Systolic Volume	right ventricular end systolic volume determined by MRI	baseline and 6 months
Change in 6 Minute Walk Distance		baseline and 6 months
Change in Tricuspid Annular Plane Systolic Excursion	Higher values indicate a better outcome.	baseline and 6 months

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Daniel C Grinnan, M.D, Virginia Commonwealth University

Publications and helpful links

General Publications

• Grinnan D, Bogaard HJ, Grizzard J, Van Tassell B, Abbate A, DeWilde C, Priday A, Voelkel NF. Treatment of group I pulmonary arterial hypertension with carvedilol is safe. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1562-4. doi: 10.1164/rccm.201311-2025LE. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: August 24, 2009
• First Submitted That Met QC Criteria: August 24, 2009
• First Posted (Estimate): August 25, 2009

Study Record Updates

• Last Update Posted (Actual): June 8, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

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: HM12120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared