Effects of Viagra on Heart Function in Patients With Heart Failure

• Sponsor: MetroHealth Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00781508
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Left Ventricular Dysfunction	Drug: sildenafil; Other: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Single Dose Sildenafil in Heart Failure Patients Improves 6-minute Walk Test by a Reduction in Left Ventricular Filling Pressure
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sildenafil Effect of oral administration of a single dose of sildenafil 50 mg on left ventricular filling pressures as evaluated 1 hr after sildenafil administration in patients with heart failure	Drug: sildenafil; Changes in left ventricular filling pressure 1 hour after the administration of a single oral dose of sildenafil 50 mg.; Other Names: Viagra ; Other: Placebo; Changes in left ventricular filling pressure 1 hour after oral administration of placebo
Placebo Comparator: placebo Inactive placebo prepared to mimic the appearance of sildenafil.	Drug: sildenafil; Changes in left ventricular filling pressure 1 hour after the administration of a single oral dose of sildenafil 50 mg.; Other Names: Viagra ; Other: Placebo; Changes in left ventricular filling pressure 1 hour after oral administration of placebo

Outcome Measures

Primary Outcome Measures

1. Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil [Left ventricular filling pressure was assessed 1 hr after oral 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

Secondary Outcome Measures

1. The Distance Walked During the 6-minute Walk Test 1 hr After the Oral Administration of Sildenafil 50 mg. [Measured 1 hr after 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MetroHealth Medical Center	Cleveland	Ohio	United States	44109

Sponsors and Collaborators

• MetroHealth Medical Center
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Robert C Bahler, MD, MetroHealth Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Bahler, Cardiologist Professor of Medicine CWRU, MetroHealth Medical Center
• ClinicalTrials.gov Identifier: NCT00781508
• Other Study ID Numbers: MO1RR000080; Grant Number UL1 RR024989; ULI RR024989
• First Posted: Oct 29, 2008
• Last Update Posted: Jul 2, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Robert Bahler, Cardiologist Professor of Medicine CWRU, MetroHealth Medical Center: heart failure, left sided; ventricular dysfunction; diastolic dysfunction; sildenafil
• Additional relevant MeSH terms: Heart Failure; Ventricular Dysfunction; Ventricular Dysfunction, Left; Sildenafil Citrate

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the Heart Failure Clinic at MetroHealth Medical Center over a 12 month interval. Recruitment was slow due to the fact that many of the patients were already perscirbed nitrates and so were ineligible for the study.
Pre-assignment Detail	More than 50 patients had to be excluded due to their already taking nitrates for their heart failure.

Arm/Group Title	Sildenafil Then Placebo	Placebo Then Sildenafil
Arm/Group Description	Effect of sildenafil on left ventricular filling pressures in patients with heart failure	Effect of Sildenafil on left ventricular function
Period Title: Overall Study
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sildenafil First Placebo Second	Placebo First Sildenafil Second	Total
Arm/Group Description	Effect of sildenafil on left ventricular filling pressures in patients with heart failure	Effect of placebo on left ventricular filling pressures in patients with heart failure	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 80%	3 60%	7 70%
>=65 years	1 20%	2 40%	3 30%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (12)	64 (12)	64 (12)
Sex: Female, Male (Count of Participants)
Female	1 20%	0 0%	1 10%
Male	4 80%	5 100%	9 90%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil
Description	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
Time Frame	Left ventricular filling pressure was assessed 1 hr after oral administration of sildenafil

Outcome Measure Data

Analysis Population Description

All patients (10) that completed the protocol were analyzed.

Arm/Group Title	Sildenafil First Then Placebo	Placebo First Then Sildenafil
Arm/Group Description	sildenafil 50 mg administered orally, placebo administered orally 48 hrs later	placebo administered orally, then sildenafil orally 48 hrs later
Measure Participants	5	5
Mean (Standard Deviation) [E/e' ratio]	16.7 (6.9)	16.4 (6.5)

2. Secondary Outcome

Title	The Distance Walked During the 6-minute Walk Test 1 hr After the Oral Administration of Sildenafil 50 mg.
Description	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.
Time Frame	Measured 1 hr after oral administration of sildenafil 50 mg

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil First Then Placebo	Placebo First Then Sildenafil
Arm/Group Description	Sildenafil 50 mg orally, placebo orally 2 days later.	placebo orally, then sildenafil 50 mg orally 2 days later.
Measure Participants	5	5
Mean (Standard Deviation) [meters]	210 (34)	219 (40)

Adverse Events

Time Frame	The study took place over a 1 year interval
Adverse Event Reporting Description	Patients were observered for any side effects or adverse reactions for 2 hrs following the administration of either sildenafil or placebo.
Arm/Group Title	Sildenafil First Then Placebo		Placebo First Then Sildenafil
Arm/Group Description	Effect of sildenafil first on left ventricular filling pressures, then effect of placebo on left ventricular filling pressure		Effect of placebo on left ventricular filing pressures, then effect of sildenafil on left ventricular filling pressure.
All Cause Mortality
	Sildenafil First Then Placebo		Placebo First Then Sildenafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sildenafil First Then Placebo		Placebo First Then Sildenafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Sildenafil First Then Placebo		Placebo First Then Sildenafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)

Limitations/Caveats

The study was limited by the small number of participants. Additionally, the inclusion criterion of a systolic pulmonary artery pressure of > 40 mmHg was no longer present in the majority of patients at the time they presented for study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.