NCT00407446

PDE5-Inhibition With Sildenafil in Chronic Heart Failure

Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 40 (planned)
• Sponsor: University of Milan · Academic / Other
• Sex: Male
• Age: 30 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

To test the hypothesis that long-term PDE5-inhibition by overexpressing the nitric oxide pathway is beneficial in chronic heart failure patients. Double-blind and placebo-controlled trial. Primary end-points: quality of life and exercise performance

Detailed description

In chronic heart failure (CHF), endothelial function (EF) deterioration and muscle underperfusion elicit ergoreflex exercise oversignaling, hyperventilation and breathlessness. PDE5 inhibition, by improving EF, might be beneficial. We tested this hypothesis in a long-term therapeutic trial. CHF patients were randomly assigned to placebo (23 cases, group 1) or sildenafil (23 cases, group 2) in addition to their current antifailure therapy, for 6 months. In group 2 and not in group 1, assessments at 3 and 6 months showed the following changes: reduction of systolic pulmonary artery pressure (-25.2 and -29.0 %), ergoreflex effect on ventilation (-66.6 and -72.5%), ventilation to CO2 production slope (VE/VCO2, -14.0 and -16.0%) and breathlessness (-29.6 and -27.1%); increase of brachial artery flow-mediated dilatation (FMD, +57.6 and +67.0%), peak exercise O2 uptake (peak VO2, +25.0 and +26.3%) and ratio of VO2 to work rate changes (VO2WR, +20.7 and +22.0%). These changes were significant at p\<0.01. In group 2 and not in group 1, a significant correlation was found, at 3 and 6 months, between changes in FMD and those in ergoreflex VE. Changes in ergoreflex correlated with those in peak VO2 and VE/VCO2 slope. No remarkable side effects were noted, but flushing in 3 patients. In CHF, benefits of sildenafil are sustained and consist of improvement in EF, modulation in ergoreflex signaling, attenuation in exercise hyperventilation and breathlessness, increase in aerobic efficiency and exercise performance. Thus, sildenafil can affect peripheral mechanisms of breathlessness and may be viewed as an effective and safe adjunct to the therapeutic armamentarium of CHF.

Conditions

• Heart Failure

Interventions

Type	Name	Description
DRUG	sildenafil

Timeline

• Start date: 2004-01-01
• Completion: 2005-02-01
• First posted: 2006-12-05
• Last updated: 2006-12-14

Locations

1 site across 1 country: Italy