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

April 23, 2012
May 22, 2014
December 2012
July 2017   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01586156 on ClinicalTrials.gov Archive Site
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PAHTCH (Carvedilol)
Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure

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.

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Interventional
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Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Pulmonary Hypertension
  • Drug: Carvedilol
    Group 1 will receive 3.125mg carvedilol twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme.
  • Drug: Carvedilol placebo
    Placebo taken twice daily for 6 months
  • 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.
    Intervention: Drug: Carvedilol
  • 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.
    Intervention: Drug: Carvedilol placebo
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
68
July 2018
July 2017   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact: Samar Farha, MD 216/444-3229 farhas@ccf.org
Contact: Jackie Sharp, CNP pylej@ccf.org
United States
 
NCT01586156
11-1198
Yes
Samar Farha, MD, The Cleveland Clinic
The Cleveland Clinic
National Institutes of Health (NIH)
Principal Investigator: Serpil Erzurum, MD The Cleveland Clinic
The Cleveland Clinic
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP