Evaluation of Sildenafil for the Treatment of Moderate Congestive Heart Failure
Recruitment status was Not yet recruiting
The purpose of the study is to evaluate whether sildenafil helps treat heart failure. Some patients with heart failure have high blood pressure in the lungs (referred to as "pulmonary hypertension"). Sildenafil is a medication that is used to treat high blood pressure in the lungs and may reduce symptoms of heart failure. Studies have looked at the short-term benefit of sildenafil in patients with congestive heart failure, but this study will look at the longer-term benefits of 12 weeks of therapy with sildenafil.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Evaluation of Sildenafil for the Treatment of Moderate Congestive Heart Failure|
- Change in 6-minute walk distance [ Time Frame: 24 hours and 3 months ] [ Designated as safety issue: No ]
- Changes in peak oxygen consumption (measured by cardiopulmonary exercise testing) [ Time Frame: 24 hours and 3 months ] [ Designated as safety issue: No ]
- Change in the level of neurohormones (b-type natriuretic peptide, catecholamines, ET-1), [ Time Frame: 24 hours and 3 months ] [ Designated as safety issue: No ]
- Change in quality of life [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||November 2008|
|Estimated Study Completion Date:||February 2011|
|Estimated Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
All patients will receive open-label treatment with sildenafil.
Sildenafil 20mg three times a day for 3 months.
Objective: To determine the effect of acute and long-term treatment with sildenafil on the clinical status of patients with moderate HF. Secondary Objectives: To determine the effect of acute and long-term treatment with sildenafil on cardiopulmonary exercise performance, the effect of acute and long-term treatment with sildenafil on neurohormonal activation, the effect of acute and long-term treatment with sildenafil on hemodynamics, and the effect of long-term treatment with sildenafil on quality of life. Background: Secondary pulmonary hypertension (PH) is a frequent manifestation of heart failure resulting in impaired vascular reactivity and permeability which contributes to the symptoms of HF. Levels of endothelin-1 (ET-1), a potent vasoconstrictor, are increased in patients with HF. At the same time, pulmonary artery nitric oxide (NO) production is decreased. NO increases concentrations of the second messenger cyclic-GMP, ultimately leading to vasodilation. This imbalance between NO-dependent vasodilation and ET-1 induced vasoconstriction likely contributes to the development of secondary pulmonary hypertension. cGMP is metabolized by the type 5 isoform of phosphodiesterase (PDE5) an enzyme that is highly expressed in the lung. Sildenafil, a selective PDE5 inhibitor, has been used extensively for the treatment of erectile dysfunction and has recently been approved for use in the treatment of PH. Recent studies of short-term administration of sildenafil in HF patients with secondary PH have demonstrated reductions in pulmonary arterial pressure, pulmonary vascular resistance, pulmonary capillary wedge pressure, and systemic vascular resistance while increasing cardiac index and exercise performance. However, it remains to be seen if sildenafil is safe and effective in the long-term treatment of heart failure. Methods: This will be an open-label, pilot study designed to evaluate the safety and efficacy of sildenafil for the treatment of moderate heart failure. The primary endpoint will be change in 6-minute walk test distance. Secondary endpoints will be changes in peak oxygen consumption (measured by cardiopulmonary exercise testing), neurohormones (b-type natriuretic peptide, catecholamines, ET-1), quality of life scores. Additionally, we will attempt to analyze responsiveness to sildenafil on the basis of PDE5 polymorphisms. Study procedures will be performed at the UNM General Clinical Research Center and the UNM Congestive Heart Failure Clinic. Patients will be hospitalized for 3 days to analyze safety and efficacy of sildenafil administered three times daily. Patients will complete exercise testing, neurohormone, and hemodynamic assessments at baseline (day 1) and following 24 hours of sildenafil treatment. The patients will then be discharged to complete a 12-week maintenance phase of treatment. At the conclusion of the maintenance phase the patients will be readmitted for 2 day to have repeat measurements performed. The main analysis will be done using paired t-tests. All statistical analysis will be performed using SAS v6.12.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00793338
|Contact: Joe R Anderson, PharmDfirstname.lastname@example.org|
|United States, New Mexico|
|Clinical Translational Science Center||Recruiting|
|Albuquerque, New Mexico, United States, 87131|
|Principal Investigator: Joe R Anderson, PharmD|
|Principal Investigator:||Joe R Anderson, PharmD||University of New Mexico College of Pharmacy|