Chronic Sildenafil Treatment in Heart Failure

This study has been completed.
Sponsor:
Information provided by:
University of Milan
ClinicalTrials.gov Identifier:
NCT00975494
First received: September 3, 2009
Last updated: September 10, 2009
Last verified: September 2009
  Purpose

In heart failure (HF), a defective nitric oxide (NO) signaling may be involved in left ventricular (LV) diastolic abnormalities and LV remodelling progression. PDE5-inhibition, by blocking NO degradation and overexpressing cellular cyclic guanosine monophosphate (cGMP) pathways might be beneficial. Several short term studies have demonstrated safety and clinical improvement in stable heart failure (HF) patients.

The purpose of this study is to test the effects on LV diastolic function, cardiac geometry and clinical status in a cohort of HF patients.


Condition Intervention Phase
Heart Failure
Drug: Sildenafil
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Chronic PDE5-Inhibition With Sildenafil Improves Diastolic Function, Cardiac Geometry and Clinical Status in Patients With Stable HF: A 1-Year Prospective Randomized, Placebo-Controlled Study

Resource links provided by NLM:


Further study details as provided by University of Milan:

Primary Outcome Measures:
  • Left ventricular diastolic function [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Functional capacity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Neurohumoral (brain natriuretic peptide) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Cardiac remodeling [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: April 2005
Study Completion Date: December 2008
Arms Assigned Interventions
Active Comparator: sildenafil
sildenafil 50 mg three times/day
Drug: Sildenafil
Placebo Comparator: Placebo
Placebo
Drug: Placebo

Detailed Description:

Heart failure (HF) is a significant health care concern that is evolving to epidemic proportions. Development of new forms of interventions remains a challenging task. An abnormal nitric oxide (NO) pathway is involved in several basic pathophysiological abnormalities encountered in HF syndrome and NO overexpression may represent a desirable therapeutic target in the cure of the disease.

PDE5-inhibition is an intriguing pharmacological strategy to enhance in vivo nitric oxide (NO) signaling by increasing the cyclic guanosine monophosphate (cGMP). availability. A number of theoretical backgrounds support the use of PDE5-inhibitors in HF and an increasing number of clinical studies have been testing PDE5-inhibition as a potential valid adjunct in the management of HF patients.

In failing hearts of animal models, PDE5-inhibition has also provided the attractive therapeutic properties to reverse left ventricular chamber remodelling by preventing and reversing LV cardiac hypertrophy and fibrosis and by protecting the myocardium from ischemia-reperfusion injury and apoptosis. There is also evidence that a defective NO activity plays an important role in the excitation-relaxation process of the failing heart, an effect explained by a defective cGMP-induced phosphorylation of troponin I, which facilitates calcium-independent diastolic cross-bridge cycling and concomitant myocardium diastolic stiffening.

No report has so far investigated whether cardiac function and, primarily, diastolic LV function may be a target of chronic PDE5-inhibition and whether any improvement in diastolic function is related to a reverse effect in cardiac geometry in patients with HF. Furthermore, it is undefined whether a favourable effect on left ventricular function may be involved in the reported changes in important clinical correlates such as functional status and quality of life. We tested these hypotheses, by addressing the effects of chronic sildenafil administration (50 mg three times/day) on diastolic function and clinical status by Tissue Doppler imaging, cardiopulmonary exercise testing and quality of life score.

  Eligibility

Ages Eligible for Study:   38 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • consent to participate in the study after detailed information about procedures, possible clinical benefits and risks;
  • negative exercise stress test prior to study initiation;
  • forced expiratory volume in 1 sec/forced vital capacity ratio>70%;
  • left ventricular ejection fraction < 45%, determined by echocardiography.

Exclusion Criteria:

  • subjects unable to complete a maximal exercise test
  • systolic blood pressure > 140 and <110 mmHg
  • diabetes mellitus
  • therapy with nitrate preparations
  • history of sildenafil intolerance
  • significant lung or valvular diseases
  • neuromuscular disorders, claudication
  • peripheral vascular disease
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00975494

Locations
Italy
University of Milano
Milano, Italy
University of Milano
Milano, Italy, 20142
Sponsors and Collaborators
University of Milan
  More Information

No publications provided by University of Milan

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Marco Guazzi (PI), University of Milano, Cardiology
ClinicalTrials.gov Identifier: NCT00975494     History of Changes
Other Study ID Numbers: 444-05
Study First Received: September 3, 2009
Last Updated: September 10, 2009
Health Authority: Italy: Ministry of Health

Keywords provided by University of Milan:
pde5-inhibition
sildenafil
LV diastolic function
heart failure patients

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 April 22, 2014