Effects of Viagra on Heart Function in Patients With Heart Failure

• ClinicalTrials.gov Identifier: NCT00781508
• Recruitment Status: Completed
• First Posted: October 29, 2008
• Results First Posted: June 23, 2014
• Last Update Posted: July 2, 2014
• Sponsor: MetroHealth Medical Center
• Collaborator: National Center for Research Resources (NCRR)
• Information provided by (Responsible Party): Robert Bahler, MetroHealth Medical Center

Tracking Information

• First Submitted Date: October 28, 2008
• First Posted Date: October 29, 2008
• Results First Submitted Date: April 22, 2013
• Results First Posted Date: June 23, 2014
• Last Update Posted Date: July 2, 2014
• Study Start Date: December 2006
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2014)

Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil [ Time Frame: 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

• Original Primary Outcome Measures (submitted: October 28, 2008): The primary outcome measure is a fall in the left ventricular filling pressure in association with administration of sildenafil [ Time Frame: The left ventricular filling presure will be assessed at 60 minutes after the administration of sildenafil ]

Current Secondary Outcome Measures (submitted: May 20, 2014)

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

• Original Secondary Outcome Measures (submitted: October 28, 2008): A secondary outcome is the distance walked with the 6-minute walk test after the administration of sildenafil [ Time Frame: Determned at the end of the 6-minute walk test ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Heart Failure
• Left Ventricular Dysfunction

Intervention

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

Study Arms

• 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
  Interventions:

  • Drug: sildenafil
  • Other: Placebo
• Placebo Comparator: placebo
  Inactive placebo prepared to mimic the appearance of sildenafil.
  Interventions:

  • Drug: sildenafil
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 20, 2014): 10
• Original Estimated Enrollment (submitted: October 28, 2008): 20
• Actual Study Completion Date: November 2009
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00781508
• Other Study ID Numbers: MO1RR000080; Grant Number UL1 RR024989 ( Other Grant/Funding Number: CWRU-CTSC ); ULI RR024989 ( Other Grant/Funding Number: NIH/NCRR CWRU-CTSC )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Robert Bahler, MetroHealth Medical Center
• Original Responsible Party: Robert C Bahler, MD, MetroHealth Medical Center
• Current Study Sponsor: MetroHealth Medical Center
• Original Study Sponsor: Same as current
• Collaborators: National Center for Research Resources (NCRR)

Investigators

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

• PRS Account: MetroHealth Medical Center
• Verification Date: June 2014