Chronic Sildenafil Treatment in Heart Failure
|ClinicalTrials.gov Identifier: NCT00975494|
Recruitment Status : Completed
First Posted : September 11, 2009
Last Update Posted : September 11, 2009
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 or disease||Intervention/treatment||Phase|
|Heart Failure||Drug: Sildenafil Drug: Placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Study Start Date :||April 2005|
|Actual Study Completion Date :||December 2008|
Active Comparator: sildenafil
sildenafil 50 mg three times/day
Placebo Comparator: Placebo
- Left ventricular diastolic function [ Time Frame: 1 year ]
- Functional capacity [ Time Frame: 1 year ]
- Quality of life [ Time Frame: 1 year ]
- Neurohumoral (brain natriuretic peptide) [ Time Frame: 1 year ]
- Cardiac remodeling [ Time Frame: 1 year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00975494
|University of Milano|
|Milano, Italy, 20142|
|University of Milano|