Clinical trial NCT00781508: Effects of Viagra on Heart Function in Patients With Heart Failure
Official title: Single Dose Sildenafil in Heart Failure Patients Improves 6-minute Walk Test by a Reduction in Left Ventricular Filling Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Left Ventricular Dysfunction
Keywords: heart failure, left sided
ventricular dysfunction
diastolic dysfunction
sildenafil
Lead sponsor: MetroHealth Medical Center
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2008-10-29
Enrollment: 10
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil
timeFrame: Left ventricular filling pressure was assessed 1 hr after oral administration of sildenafil
Secondary outcomes:
measure: The Distance Walked During the 6-minute Walk Test 1 hr After the Oral Administration of Sildenafil 50 mg.
timeFrame: Measured 1 hr after oral administration of sildenafil 50 mg
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
Study officials:
affiliation: MetroHealth Medical Center
name: Robert C Bahler, MD
role: PRINCIPAL_INVESTIGATOR
References: