Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT00793338 |
| Other study ID # |
HRRC 05-369 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
November 2008 |
| Est. completion date |
February 2011 |
Study information
| Verified date |
June 2023 |
| Source |
University of New Mexico |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
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.
