Text Size

PDE5-Inhibition With Sildenafil in Chronic Heart Failure

This study has been completed.
Sponsor:
Information provided by:
University of Milan
ClinicalTrials.gov Identifier:
NCT00407446
First received: December 1, 2006
Last updated: December 12, 2006
Last verified: December 2006
History of Changes
  Purpose

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


Condition Intervention Phase
Heart Failure
 Drug: sildenafil
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Milan:

Primary Outcome Measures:
  • Exercise performance, ventilation efficiency, symptoms

Secondary Outcome Measures:
  • quality of life

Estimated Enrollment: 40
Study Start Date: January 2004
Estimated Study Completion Date: February 2005
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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligibility criteria were: consent to participate in the study after detailed information about procedures, possible clinical benefits and risks; ability to complete a maximal exercise test; forced expiratory volume in 1 sec/forced vital capacity ratio>70%; left ventricular ejection fraction  45%, determined by echocardiography.

Exclusion Criteria:

  • Patients were not recruited if they had systolic blood pressure > 140 and <110 mmHg, diabetes mellitus, therapy with nitrate preparations, history of sildenafil intolerance, significant lung or valvular diseases, neuromuscular disorders, exercise-induced myocardial ischemia, atrial fibrillation (6), claudication, peripheral vascular disease.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00407446

Locations
Italy
Marco Guazzi, MD, PhD University of Milano
Milano, Italy, 20141
Sponsors and Collaborators
University of Milan
Investigators
Principal Investigator: Marco Guazzi, MD University of Milano
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00407446     History of Changes
Other Study ID Numbers: 124-04
Study First Received: December 1, 2006
Last Updated: December 12, 2006
Health Authority: Italy: Ministry of Health

Keywords provided by University of Milan:
PDE5 inhibition
chronic heart failure
endothelial function
exercise ventilation

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
 Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2013