Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study) - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Collaborator:	Pfizer
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00763867

Purpose

Diastolic heart failure (DHF), which affects older individuals and women at a disproportionate rate, is a condition that can lead to shortness of breath and fluid build-up in the lungs. This study will evaluate the effectiveness of the medication sildenafil at improving exercise ability and health outcomes in people with DHF.

Condition	Intervention	Phase
Heart Failure	Drug: Sildenafil Drug: Placebo Comparator	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment
Official Title:	Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX)

Resource links provided by NLM:

MedlinePlus related topics: Exercise and Physical Fitness Heart Failure

Drug Information available for: Sildenafil Sildenafil citrate

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Change in exercise capacity, as determined by peak oxygen uptake [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in peak oxygen uptake during exercise [ Time Frame: Measured at Week 12 ] [ Designated as safety issue: No ]
Change in submaximal exercise capacity, as determined by 6-minute walk test [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]
Change in a composite score reflective of clinical status [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment:	190
Study Start Date:	September 2008
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will receive sildenafil	Drug: Sildenafil Participants will receive 20 mg of sildenafil three times a day for 12 weeks, followed by 60 mg of sildenafil three times a day for 12 weeks
2: Placebo Comparator Participants will receive placebo	Drug: Placebo Comparator Participants will receive 20 mg of placebo three times a day for 12 weeks, followed by 60 mg of placebo three times a day for 12 weeks

Detailed Description:

DHF is a condition in which one of the chambers of the heart, the left ventricle, loses its ability to relax completely because the muscle has become too stiff. When this occurs, the heart is unable to properly fill with blood, which can lead to decreased blood circulation. People with DHF may experience shortness of breath and pulmonary congestion, which is an abnormal build-up of fluid in the lungs. Current treatment for DHF includes guidelines/recommendations to lower blood pressure, stop smoking, and lose weight, but there are no medications available to specifically treat DHF. Sildenafil, commonly known as Revatio or Viagra, is a medication that increases the supply of blood to the lungs and reduces the workload of the heart. Preliminary studies have shown that sildenafil may be beneficial at improving heart and lung function in people with DHF, but more research is needed to confirm these findings. The purpose of this study is to determine if sildenafil can improve exercise ability and health outcomes in people with DHF.

This 24-week study will enroll people with DHF. Participants will be randomly assigned to receive either sildenafil or placebo three times a day for 24 weeks. Participants will attend study visits at baseline and Weeks 1, 4, 12, 13, and 24. At most study visits, the following procedures will occur: physical exam, medical history review, questionnaires, blood collection, 6-minute walk test to measure endurance, and an exercise test. At baseline and Week 24, participants will also undergo an electrocardiogram, which will measure the electrical activity of the heart, and a cardiac magnetic resonance imaging (MRI) procedure and an echocardiogram, which will both obtain pictures of the heart. At Weeks 3, 8, 16, and 20, study researchers will call participants to collect health information.

Eligibility

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

Criteria

Inclusion Criteria:

Previous clinical diagnosis of heart failure with current New York Heart Association (NYHA) Class II-IV symptoms
Has experienced at least one of the following in the 12 months before study entry:
- Hospitalization for decompensated heart failure
- Acute treatment with intravenous loop diuretic or hemofiltration
- Mean pulmonary capillary wedge pressure greater than 15 mm Hg or left ventricular end diastolic pressure (LVEDP) greater than 18 mm Hg at catheterization for dyspnea
- Long term treatment with a loop diuretic and chronic diastolic dysfunction on echocardiography, as determined by left atrial enlargement
Left ventricular ejection fraction greater than or equal to 50%, as determined by a clinical echocardiogram or ventriculogram in the 12 months before study entry
Receiving stable medical therapy in the 30 days before study entry, as determined by no addition or removal of angiotensin converting enzyme inhibitor (ACE), angiotensin receptor blocker (ARB), beta-blockers, or calcium channel blockers (CCB) and no change in dosage of ACE, ARBs, beta-blockers, or CCBs of more than 100%

Exclusion Criteria:

Has a neuromuscular, orthopedic, or other non-cardiac condition that prevents individual from exercise testing on a bicycle ergometer or from walking in a hallway
Non-cardiac condition that limits life expectancy to less than 1 year at the time of study entry, based on the judgment of the physician
Current or anticipated future need for nitrate therapy
Valve disease (i.e., greater than mild aortic or mitral stenosis; greater than moderate aortic or mitral regurgitation)
Hypertrophic cardiomyopathy
Infiltrative or inflammatory myocardial disease (e.g., amyloid, sarcoid)
Pericardial disease
Primary pulmonary arteriopathy
Has experienced a heart attack or unstable angina, or has undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) in the 60 days before study entry, or requires either PTCA or CABG at the time of study entry
Other clinically important causes of dyspnea, such as morbid obesity or significant lung disease, as defined by clinical judgment or use of steroids or oxygen for lung disease
Systolic blood pressure less than 110 mm Hg or greater than 180 mm Hg
Diastolic blood pressure less than 40 mm Hg or greater than 100 mm Hg
Resting heart rate (HR) greater than 100 bpm
History of reduced ejection fraction (less than 50%)
Implanted metallic device that will interfere with MRI examination (in people without atrial fibrillation)
Severe kidney dysfunction (estimated glomerular filtration rate [GFR] less than 20 ml/min/1.73m2 by modified modification of diet in renal disease [MDRD] equation)
Pregnant or not using an effective form of contraception
Hemoglobin level of less than 10 g/dL
Taking alpha antagonists or cytochrome P450 3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, saquinavir, cimetidine, or serum protease inhibitors for HIV)
Retinitis pigmentosa, previous diagnosis of nonischemic optic neuropathy, untreated proliferative retinopathy, or unexplained visual disturbance
Sickle cell anemia, multiple myeloma, leukemia, or penile deformities that increase the risk for priapism (e.g., angulation, cavernosal fibrosis, Peyronie's disease)
Severe liver disease (aspartate aminotransferase [AST] level greater than three times the normal limit, alkaline phosphatase or bilirubin greater than two times the normal limit)
In being consistent with American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, people with dyspnea and risk factors for coronary artery disease should have had a stress test and those people with a clinically indicated stress test demonstrating significant ischemia in the 1 year before study entry will be excluded.
Listed for heart transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00763867

Locations

United States, Georgia
Morehouse School of Medicine	Recruiting
Atlanta, Georgia, United States, 30310
Contact: Elizabeth Ofili, MD 404-752-1970 eofili@msm.edu
Contact: Brenda Lankford, RN, PhD 404-756-1377 blankford@msm.edu
Principal Investigator: Elizabeth Ofili, MD
Sub-Investigator: Anekwe Onwuanyi, MD
Sub-Investigator: Adefisayo Oduwole, MD
United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lynne W. Stevenson, MD 617-732-7406 lstevenson@partners.org
Contact: Jerry Cornish jcornish@partners.org
Principal Investigator: Lynne W. Stevenson, MD
Sub-Investigator: Michael Givertz, MD
Sub-Investigator: Marc Semigran, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Margaret M. Redfield, MD 507-284-1281 redfield.margaret@mayo.edu
Contact: Jilian Foxen 507-284-1281 foxen.jilian@mayo.edu
Principal Investigator: Margaret M. Redfield, MD
Sub-Investigator: John Burnett, MD
Sub-Investigator: Horng Chen, MD
Sub-Investigator: Lisa Costello, MD
Sub-Investigator: John Schirger, MD
Minnesota Heart Failure Network	Recruiting
Minneapolis, Minnesota, United States, 55415
Contact: Steven R. Goldsmith, MD 612-873-2875 srg_hcmc@yahoo.com
Contact: Shari Mackedanz, RN, BSN, CCRC 612-873-5195 shari.mackedanz@hcmed.org
Principal Investigator: Steven R. Goldsmith, MD
Sub-Investigator: Bradley Bart, MD
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27705
Contact: Christopher O'Connor, MD 919-880-6787 oconn002@mc.duke.edu
Contact: Renee Story 919-681-6195 story003@mc.duke.edu
Principal Investigator: Christopher O'Conner, MD
Sub-Investigator: Michael Felker, MD, MHS
Sub-Investigator: Joseph Rogers, MD
Sub-Investigator: Carmelo Milano, MD
United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Douglas Mann, MD 713-798-0285 dmann@bcm.tmc.edu
Contact: Mary Soliz msoliz@bcm.tmc.edu
Principal Investigator: Doug Mann, MD
Sub-Investigator: Anita Deswal, MD, MPH
United States, Utah
University of Utah Health Sciences Center	Recruiting
Murray, Utah, United States, 84107
Contact: David Bull, MD 801-581-5311 david.bull@hsc.utah.edu
Contact: Bev Campbell, MN, CCRC 801-507-4706 bev.campbell@imail.org
Principal Investigator: David Bull, MD
Sub-Investigator: Dale Renlund, MD
Sub-Investigator: Edward Gilbert
United States, Vermont
University of Vermont - Fletcher Allen Health Care	Recruiting
Burlington, Vermont, United States, 05401
Contact: Martin LeWinter, MD 802-847-2879 martin.lewinter@vtmednet.org
Contact: Michaelanne Rowen, RN 802-847-4746 michaelanne.rowen@vtmednet.org
Principal Investigator: Martin LeWinter, MD
Sub-Investigator: Markus Meyer, MD
Sub-Investigator: Richard Pratley, MD
Sub-Investigator: Peter VanBuren, MD
Sub-Investigator: Burton Sobel, MD
Canada, Quebec
Montreal Heart Institute	Recruiting
Montreal, Quebec, Canada, H1T - 1C8
Contact: Jean Rouleau, MD 514-343-6351 jean.rouleau@umontreal.ca
Contact: Lucette Whittom, RN 514-376-3330 ext 3931 lucette.whittom@icm-mhi.org
Principal Investigator: Jean Rouleau, MD
Sub-Investigator: Normand Racine, MD
Sub-Investigator: Michel White, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Pfizer

Investigators

Principal Investigator:	Kerry L. Lee, PhD	Duke University
Study Chair:	Eugene Braunwald, MD	Harvard University

More Information

No publications provided

Responsible Party:	Duke Clinical Research Center ( Kerry L. Lee, PhD )
Study ID Numbers:	521, U01 HL084904-01
Study First Received:	September 30, 2008
Last Updated:	February 23, 2009
ClinicalTrials.gov Identifier:	NCT00763867 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Heart Failure, Diastolic
Decompensated Heart Failure
Sildenafil
Exercise Capacity

Additional relevant MeSH terms:

Vasodilator Agents
Heart Failure, Diastolic
Heart Failure
Phosphodiesterase Inhibitors
Heart Diseases
Molecular Mechanisms of Pharmacological Action

Therapeutic Uses
Enzyme Inhibitors
Sildenafil
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 30, 2009