PAHTCH (Carvedilol)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by The Cleveland Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Samar Farha, MD, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01586156
First received: April 23, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

Pulmonary arterial hypertension (PAH) is a serious condition characterized by endothelial dysfunction leading to pulmonary vascular constriction, smooth muscle and endothelial proliferation, and progressive right-sided heart failure. The severity of pulmonary hypertension is mostly determined by the response of the right ventricle (RV) to the increased afterload or pulmonary pressures, and RV failure is the leading cause of death in PAH. Most accepted therapies for PAH have been aimed at vasodilation of the pulmonary vasculature, and there has been little thought that PAH patients would benefit from traditional left heart failure treatments. A cornerstone therapy in left heart failure is £]-adrenergic receptor blockade because of its ability to reverse cardiac remodeling and improve clinical outcomes, despite decades of concern regarding its propensity to exacerbate heart failure. It has been reported to reduce mortality by about 30% in patients, and while the precise mechanisms that contribute to its beneficial effects remain to be elucidated, there is evidence that patients with underlying contractile reserve (i.e., via recruitment of viable myocardium with £]-adrenergic receptor stimulation) may experience greater recovery of their cardiac function. In a study using rats with pulmonary hypertension treated with £] blocker, RV function improved, and maladaptive myocardial remodeling was prevented.


Condition Intervention
Pulmonary Hypertension
Drug: Carvedilol
Drug: Carvedilol placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Biochemical abnormalities (HIF activation, NO synthesis, beta-adrenergic receptor recovery) [ Time Frame: Throughout 1-5 years of the program ] [ Designated as safety issue: No ]
    We hypothesize that use of carvedilol in patients with PAH will improve right and left ventricular function, decrease right and left ventricular size, and improve exercise and functional capacity.


Estimated Enrollment: 68
Study Start Date: December 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Open Label Carvedilol
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study.
Drug: Carvedilol
Group 1 will receive 3.125mg carvedilol twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme.
Placebo Comparator: Placebo Arm
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Drug: Carvedilol placebo
Placebo taken twice daily for 6 months

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women age 18 or older not greater than age 65 years
  • Diagnosis of pulmonary arterial hypertension class 1, 3, 4, 5 (Dana Point 2008)
  • NYHA/WHO Class I-III
  • PAH medications must have been initiated according to the latest consensus statement recommendations and remained stable for the last 30 days
  • Women of child-bearing age must use a double-barrier local contraception till completion of the study
  • Subjects must demonstrate understanding of the study, sign the informed consent, and have a reliable method of communication for contact and ability to comply with the study requirements

Exclusion Criteria:

  • Participation in any other treatment studies during enrollment
  • Significant illness in the past 30 days requiring hospitalization
  • Hepatic insufficiency (transaminase levels > 4 fold the upper limit of normal or bilirubin > 2 fold the upper limit of normal),
  • History of HIV, Hepatitis B or C
  • Serum creatinine > 2.8 mg/dl
  • Pregnancy, breast-feeding, or lack of safe contraception
  • Acute decompensated heart failure within past 30 days
  • Known allergy or intolerance to carvedilol or other β blockers
  • Significant, persistent bradycardia (resting heart rate < 50 bpm) or hypotension (systolic blood pressure < 100 mmHg or mean blood pressure < 70 mmHg) at the time of enrollment
  • Second or third-degree AV block without pacemaker
  • Use of CYP2D6 isoenzyme inhibitors (such as quinidine, fluoxetine, paroxetine, propafenone) which increase drug levels and result in greater vasodilating effects and hypotension
  • Use of hypotensive drugs that deplete catecholamines (such as reserpine and monoamine oxidase inhibitors) which may lead to greater signs of hypotension or bradycardia
  • Other medical and psychosocial conditions as determined by principal investigator deemed unsuitable for enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01586156

Contacts
Contact: Samar Farha, MD 216/444-3229 farhas@ccf.org
Contact: Jackie Sharp, CNP pylej@ccf.org

Locations
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Samar Farha, MD    216-444-3229    farhas@ccf.org   
Contact: Jackie Sharp, CNP       pyleJ@ccf.org   
Principal Investigator: Serpil Erzurum, MD         
Sub-Investigator: Samar Farha, MD         
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Principal Investigator: Serpil Erzurum, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: Samar Farha, MD, Clinical Study Director, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01586156     History of Changes
Other Study ID Numbers: 11-1198
Study First Received: April 23, 2012
Last Updated: May 22, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Carvedilol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists

ClinicalTrials.gov processed this record on July 29, 2014