Effects of Viagra on Heart Function in Patients With Heart Failure

Heart Failure Clinical Trial

Official title:

Single Dose Sildenafil in Heart Failure Patients Improves 6-minute Walk Test by a Reduction in Left Ventricular Filling Pressure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00781508
• Other study ID #: MO1RR000080
• Secondary ID: Grant Number UL1
• Status: Completed
• Phase: Phase 4
• First received: October 28, 2008
• Last updated: June 23, 2014
• Start date: December 2006
• Est. completion date: November 2009

Study information

• Verified date: June 2014
• Source: MetroHealth Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Sildenafil (Viagra) is known to reduce pulmonary hypertension. Heart failure patients also have pulmonary hypertension and several recent reports have shown that sildenafil leads to an improvement in their exercise capacity. In these studies sildenafil caused a reduction in the pulmonary and systemic vascular resistances, improved pulmonary gas diffusion and perhaps increased cardiac output. It is uncertain if left ventricular filling pressures are reduced and whether there is improvement in left ventricular relaxation. The investigators hypothesize that in heart failure patients the improvement in exercise capacity associated with sildenafil is related to a significant reduction in left ventricular filling pressures. The investigators propose to study 20 patients with stable but moderately symptomatic heart failure. The study design is a randomized cross-over trial of the administration of a single dose of sildenafil 50 mg or a matching placebo. Exercise capacity will be determined before and after the oral administration of sildenafil 50 mg or placebo. Left ventricular filling pressures will be assessed by Doppler echocardiography and the serum level of B-type natriuretic peptide (BNP is known to increase with higher left ventricular filling pressures). After an initial echocardiogram and performing a 6 minute walk test, the patient will then be given either sildenafil or a matching placebo in a randomized double-blind fashion. One hr later a blood sample for serum BNP, the echocardiogram and the 6 minute walk test will be repeated.

Description:

Sildenafil (Viagra) has been extensively studied in patients with idiopathic pulmonary hypertension. It reduces pulmonary vascular resistance, improves exercise capacity and is now an approved therapy for this condition. Heart failure (HF) patients also have pulmonary hypertension and several recent reports have shown that sildenafil leads to an improvement in their exercise capacity. In HF sildenafil causes a reduction in the pulmonary and systemic vascular resistances, improves pulmonary gas diffusion and perhaps increases cardiac output. It is uncertain if left ventricular filling pressures are reduced and whether there is improvement in left ventricular relaxation. We hypothesize that in HF patients the improvement in exercise capacity associated with sildenafil is related to a significant reduction in left ventricular filling pressures. We propose to study 10 patients with stable, symptomatic HF Class III. The study design is a randomized cross-over assignment of the administration of a single oral dose of sildenafil 50 mg or a matching placebo. Patients will be excluded if walking is impaired due to non-cardiac conditions or if they are taking nitrates. Exercise capacity will be determined before and 60 minutes after the oral administration of sildenafil 50 mg or placebo. The difference in the standardized 6 minute walk test (distance patient is able to walk over a 6 minute interval) will be used to assess exercise capacity. Left ventricular filling pressures will be assessed by Doppler echocardiography and the serum level of B-type natriuretic peptide (BNP). Evaluation of left ventricular relaxation will be determined by Doppler echocardiography techniques. Each patient will have a blood sample for BNP, an initial echocardiogram and perform a 6 minute walk test. They will then be given a single dose of either sildenafil or a matching placebo in a randomized double-blind fashion. The randomization was performed so that half of the group would receive the placebo on the initial test and sildenafil on the subsequent test and the other half would have the reverse sequence. One hr after the medication/placebo administration a blood sample for serum BNP, the echocardiogram and the 6 minute walk test will be repeated. After completion of the above protocol, the patient will return in 48 hrs and the protocol will be repeated with the predetermined assignment of either placebo or sildenafil.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 75 Years

Eligibility

Inclusion Criteria:

• Adults with Class III congestive heart failure and impaired left ventricular systolic function.

• A prior BNP level = 200 pg/mL.

• Previously documented systolic pulmonary artery pressure >40 mmHg.

• Clinically stable for a minimum of 6 weeks.

• Able to give informed consent,

Exclusion Criteria:

• Unable to give informed consent.

• Currently taking nitrates.

• A HF exacerbation within the past 6 weeks.

• Co-morbid conditions that could limit their walking.

• Have a resting systolic blood pressure < 110 mmHg

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Left Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Drug:
• sildenafil
Changes in left ventricular filling pressure 1 hour after the administration of a single oral dose of sildenafil 50 mg.

Other:
• Placebo
Changes in left ventricular filling pressure 1 hour after oral administration of placebo

Locations

Country	Name	City	State
United States	MetroHealth Medical Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
MetroHealth Medical Center	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil	Left ventricular filling pressure was assessed by the ratio of the velocity of early mitral inflow (E) divided by the early tissue velocity (e). E/e	Left ventricular filling pressure was assessed 1 hr after oral administration of sildenafil	No
Secondary	The Distance Walked During the 6-minute Walk Test 1 hr After the Oral Administration of Sildenafil 50 mg.	A standardized course was used to determine the distance walked (meters) during a 6 min walk supervised by a nurse trained in performance of the test.	Measured 1 hr after oral administration of sildenafil 50 mg	No