Carvedilol PAH A Pilot Study of Efficacy and Safety

NCT02120339 | Terminated Phase 1 DMC

• 1 other identifier: PAH
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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

Conditions

Pulmonary Hypertension; Cardiac MRI <40

Keywords

Hypertension; PAH

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline and 6 months

Secondary Outcomes (1)

• Absence of Adverse Events

  6 months

Study Arms (1)

Carvedilol

EXPERIMENTAL

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

Drug: Carvedilol

Interventions

Carvedilol DRUG

Carvedilol

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Related Publications (1)

• 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.

  PMID: 34259020 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary; Hypertension

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Thenappan Thenappan, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2014
• First Posted: April 22, 2014
• Study Start: May 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: July 12, 2019

Record last verified: 2019-07

Locations

US (1)