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.
|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|
- 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.
|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)|
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.
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01586156
|Contact: Samar Farha, MDfirstname.lastname@example.org|
|Contact: Jackie Sharp, CNPemail@example.com|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|Contact: Samar Farha, MD 216-444-3229 firstname.lastname@example.org|
|Contact: Jackie Sharp, CNP pyleJ@ccf.org|
|Principal Investigator: Serpil Erzurum, MD|
|Sub-Investigator: Samar Farha, MD|
|Principal Investigator:||Serpil Erzurum, MD||The Cleveland Clinic|