PDE5-Inhibition With Sildenafil in Chronic Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00407446
Recruitment Status : Completed
First Posted : December 5, 2006
Last Update Posted : December 14, 2006
Information provided by:
University of Milan

Brief 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

Condition or disease Intervention/treatment Phase
Heart Failure Drug: sildenafil Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure
Study Start Date : January 2004
Estimated Study Completion Date : February 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Primary Outcome Measures :
  1. Exercise performance, ventilation efficiency, symptoms

Secondary Outcome Measures :
  1. quality of life

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00407446

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

Publications: Identifier: NCT00407446     History of Changes
Other Study ID Numbers: 124-04
First Posted: December 5, 2006    Key Record Dates
Last Update Posted: December 14, 2006
Last Verified: December 2006

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 Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents