PDE5-Inhibition With Sildenafil in Chronic Heart Failure
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
sildenafil
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring PDE5 inhibition, chronic heart failure, endothelial function, exercise ventilation
Eligibility 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.
Sites / Locations
- Marco Guazzi, MD, PhD University of Milano
Outcomes
Primary Outcome Measures
Exercise performance, ventilation efficiency, symptoms
Secondary Outcome Measures
quality of life
Full Information
NCT ID
NCT00407446
First Posted
December 1, 2006
Last Updated
December 12, 2006
Sponsor
University of Milan
1. Study Identification
Unique Protocol Identification Number
NCT00407446
Brief Title
PDE5-Inhibition With Sildenafil in Chronic Heart Failure
Official Title
Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
December 2006
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2005 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of Milan
4. Oversight
5. Study Description
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
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 (VO2WR, +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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
PDE5 inhibition, chronic heart failure, endothelial function, exercise ventilation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
40 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
sildenafil
Primary Outcome Measure Information:
Title
Exercise performance, ventilation efficiency, symptoms
Secondary Outcome Measure Information:
Title
quality of life
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marco Guazzi, MD
Organizational Affiliation
University of Milano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marco Guazzi, MD, PhD University of Milano
City
Milano
ZIP/Postal Code
20141
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
15619391
Citation
Katz SD, Parker JD, Glasser DB, Bank AJ, Sherman N, Wang H, Sweeney M. Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure. Am J Cardiol. 2005 Jan 1;95(1):36-42. doi: 10.1016/j.amjcard.2004.08.060.
Results Reference
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PDE5-Inhibition With Sildenafil in Chronic Heart Failure
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