Evaluation of Sildenafil for the Treatment of Moderate Congestive Heart Failure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by University of New Mexico.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
University of New Mexico
ClinicalTrials.gov Identifier:
NCT00793338
First received: November 17, 2008
Last updated: November 18, 2008
Last verified: November 2008
  Purpose

The purpose of the study is to evaluate whether sildenafil helps treat heart failure. Some patients with heart failure have high blood pressure in the lungs (referred to as "pulmonary hypertension"). Sildenafil is a medication that is used to treat high blood pressure in the lungs and may reduce symptoms of heart failure. Studies have looked at the short-term benefit of sildenafil in patients with congestive heart failure, but this study will look at the longer-term benefits of 12 weeks of therapy with sildenafil.


Condition Intervention Phase
Heart Failure
Drug: Sildenafil
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Sildenafil for the Treatment of Moderate Congestive Heart Failure

Resource links provided by NLM:


Further study details as provided by University of New Mexico:

Primary Outcome Measures:
  • Change in 6-minute walk distance [ Time Frame: 24 hours and 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in peak oxygen consumption (measured by cardiopulmonary exercise testing) [ Time Frame: 24 hours and 3 months ] [ Designated as safety issue: No ]
  • Change in the level of neurohormones (b-type natriuretic peptide, catecholamines, ET-1), [ Time Frame: 24 hours and 3 months ] [ Designated as safety issue: No ]
  • Change in quality of life [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2008
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sildenafil
All patients will receive open-label treatment with sildenafil.
Drug: Sildenafil
Sildenafil 20mg three times a day for 3 months.
Other Names:
  • Sildenafil
  • Heart failure
  • Cardiopulmonary exercise test

Detailed Description:

Objective: To determine the effect of acute and long-term treatment with sildenafil on the clinical status of patients with moderate HF. Secondary Objectives: To determine the effect of acute and long-term treatment with sildenafil on cardiopulmonary exercise performance, the effect of acute and long-term treatment with sildenafil on neurohormonal activation, the effect of acute and long-term treatment with sildenafil on hemodynamics, and the effect of long-term treatment with sildenafil on quality of life. Background: Secondary pulmonary hypertension (PH) is a frequent manifestation of heart failure resulting in impaired vascular reactivity and permeability which contributes to the symptoms of HF. Levels of endothelin-1 (ET-1), a potent vasoconstrictor, are increased in patients with HF. At the same time, pulmonary artery nitric oxide (NO) production is decreased. NO increases concentrations of the second messenger cyclic-GMP, ultimately leading to vasodilation. This imbalance between NO-dependent vasodilation and ET-1 induced vasoconstriction likely contributes to the development of secondary pulmonary hypertension. cGMP is metabolized by the type 5 isoform of phosphodiesterase (PDE5) an enzyme that is highly expressed in the lung. Sildenafil, a selective PDE5 inhibitor, has been used extensively for the treatment of erectile dysfunction and has recently been approved for use in the treatment of PH. Recent studies of short-term administration of sildenafil in HF patients with secondary PH have demonstrated reductions in pulmonary arterial pressure, pulmonary vascular resistance, pulmonary capillary wedge pressure, and systemic vascular resistance while increasing cardiac index and exercise performance. However, it remains to be seen if sildenafil is safe and effective in the long-term treatment of heart failure. Methods: This will be an open-label, pilot study designed to evaluate the safety and efficacy of sildenafil for the treatment of moderate heart failure. The primary endpoint will be change in 6-minute walk test distance. Secondary endpoints will be changes in peak oxygen consumption (measured by cardiopulmonary exercise testing), neurohormones (b-type natriuretic peptide, catecholamines, ET-1), quality of life scores. Additionally, we will attempt to analyze responsiveness to sildenafil on the basis of PDE5 polymorphisms. Study procedures will be performed at the UNM General Clinical Research Center and the UNM Congestive Heart Failure Clinic. Patients will be hospitalized for 3 days to analyze safety and efficacy of sildenafil administered three times daily. Patients will complete exercise testing, neurohormone, and hemodynamic assessments at baseline (day 1) and following 24 hours of sildenafil treatment. The patients will then be discharged to complete a 12-week maintenance phase of treatment. At the conclusion of the maintenance phase the patients will be readmitted for 2 day to have repeat measurements performed. The main analysis will be done using paired t-tests. All statistical analysis will be performed using SAS v6.12.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than 18 years
  • Diagnosis of chronic heart failure with an ejection fraction less than or equal to 45% per either an echocardiogram, nuclear cardiolyte stress test, or cardiac catheterization performed within the past 6 months.
  • New York Heart Association Functional Class III
  • Must be on optimal heart failure therapy according to AHA/ACC heart failure guidelines, including treatment with ACEI and beta-blocker therapy, or have documented rationale for variation, including intolerance, contraindication, patient preference, or personal physician's judgment

Exclusion Criteria:

  • Comorbid disease or behavioral or other limitations that: 1) interfere with performing exercise test, or 2) prevent completion of 12 week study
  • Currently pregnant or intent to become pregnant in the next 12 weeks or currently breastfeeding.
  • Major cardiovascular event or cardiovascular procedure within the prior 6 weeks
  • History of Chronic Obstructive Pulmonary Disease or Reactive Airway Disease
  • Known hypersensitivity to sildenafil
  • Current use of medications known to be a potent inhibitor of CYP3A4 (e.g., ritonavir, ketoconazole, itraconazole)
  • Current or recent (within 6 months) use of organic nitrate medications (e.g. isosorbide dinitrate, sublingual nitroglycerin)
  • Known diagnosis of pulmonary veno-occlusive disease or non-arteritic anterior ischemic optic neuropathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793338

Contacts
Contact: Joe R Anderson, PharmD 505-272-3664 janderson@salud.unm

Locations
United States, New Mexico
Clinical Translational Science Center Recruiting
Albuquerque, New Mexico, United States, 87131
Principal Investigator: Joe R Anderson, PharmD         
Sponsors and Collaborators
University of New Mexico
Investigators
Principal Investigator: Joe R Anderson, PharmD University of New Mexico College of Pharmacy
  More Information

No publications provided

Responsible Party: Joe R. Anderson, PharmD, University of New Mexico College of Pharmacy
ClinicalTrials.gov Identifier: NCT00793338     History of Changes
Other Study ID Numbers: HRRC 05-369
Study First Received: November 17, 2008
Last Updated: November 18, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by University of New Mexico:
Heart failure
Sildenafil
Cardiopulmonary exercise test
quality of life
6 minute walk test

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 11, 2014