Heart FailurePhase 3RELAXNCT00763867
Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study)
A Phase 3 study testing Sildenafil in people with Heart Failure, run by Duke University at 10 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 216 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Sep 2008to Sep 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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)
Show all 24Show fewer
- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
Morehouse School of Medicine
Atlanta, Georgia, 30310
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Vermont - Fletcher Allen Health Care
Burlington, Vermont, 05401
Duke University Medical Center
Durham, North Carolina, 27705
Baylor College of Medicine
Houston, Texas, 77030
Minnesota Heart Failure Network
Minneapolis, Minnesota, 55415
University of Utah Health Sciences Center
Murray, Utah, 84107
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX)
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Placebo, Sildenafil
- Keywords
- Heart Failure, Diastolic, Decompensated Heart Failure, Sildenafil, Exercise Capacity
- Medical subject headings
- Heart Failure, Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Sugar pill to mimic Sildenafil
SildenafilDrug
Also called Active Sildenafil
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks Receives: Drug: Placebo |
| Sildenafil | Experimental | Sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exercise Capacity, as Determined by Peak Oxygen Uptake
Measured: Change from Baseline to Week 24
Secondary outcomes (10)
Exercise Capacity, as Determined by Peak Oxygen Uptake
Measured: Change from Baseline to Week 12
Exercise Capacity as Determined by Walk Distance
6 Minute Walk Distance
Measured: Change from Baseline to Week 12
Composite Score Reflective of Clinical Status
Participants ranked sequentially with ranking stratified in one of three tiers based on:
- Death (lowest tier) The person with the shortest time from randomization to death is given the lowest rank within the tier.
- Hospitalizations due to cardiovascular or renal causes (middle tier) For patients alive, the ranking within this tier is based on time to hospitalization from randomization date. The person with the first cardiovascular or renal cause hospitalization will be given the lowest rank within the tier.
- Change in Minnesota Living with Heart Failure Questionnaire (MLWHFQ) from baseline (highest tier)
The use of three tiers within the ranking reflects the greater adverse impact of death or cardiovascular hospitalization on clinical status without an arbitrary assignment as to the relative value of these events in relation to changes in quality of life. Rank order: 1-189 (higher values are better)
Measured: Measured at Week 24
Exercise Capacity as Determined by Walk Distance
6 minute walk distance
Measured: Change from Baseline to Week 24
Cardiopulmonary Exercise Test (CPET) Duration
To interpret the CPET Exercise Duration change endpoints, an increase in exercise duration between Baseline and Week 12/Week 24 is considered to be an improvement
Measured: Change from Baseline to Week 12
Cardiopulmonary Exercise Test (CPET) Duration
To interpret the CPET Exercise Duration change endpoints, an increase in exercise duration between Baseline and Week 12/Week 24 is considered to be an improvement
Measured: Change from Baseline to Week 24
Ventilatory Anaerobic Threshold
To interpret the Ventilatory Anaerobic Threshold (VAT) change endpoints, an increase in VAT between Baseline and Week 12/Week 24 is considered to be an improvement
Measured: Change from Baseline to Week 12
Ventilatory Anaerobic Threshold
To interpret the Ventilatory Anaerobic Threshold (VAT) change endpoints, an increase in VAT between Baseline and Week 12/Week 24 is considered to be an improvement
Measured: Change from Baseline to Week 24
Minnesota Living With Heart Failure Questionnaire (MLWHFQ)
The MLWHFQ is a self-administered, disease-specific measure of health related quality of life (QOL) that assesses patients perceptions of the influence of heart failure on physical, socioeconomic and psychological aspects of life. Patients respond to 21 items using a six-point response scale (0-5). The total summary score can range from 0-105 with a lower score reflecting better heart failure related QOL. Two sub-scale scores reflect physical (8 items) and emotional (5 items) impairment.
Total score: 0 - 105 Physical subscore: 0 - 40 Emotional subscore: 0 - 25
Measured: Change from Baseline to Week 12
Minnesota Living With Heart Failure Questionnaire
The MLWHFQ is a self-administered, disease-specific measure of health related quality of life (QOL) that assesses patients perceptions of the influence of heart failure on physical, socioeconomic and psychological aspects of life. Patients respond to 21 items using a six-point response scale (0-5). The total summary score can range from 0-105 with a lower score reflecting better heart failure related QOL. Two sub-scale scores reflect physical (8 items) and emotional (5 items) impairment.
Measured: Change from Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2008 (estimated)
- Study startSep 2008
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 216 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Pfizer
- Responsible party
- Sponsor
- Investigators
- Kerry L. Lee, PhD, Principal investigator, Duke Clinical Research InstituteEugene Braunwald, MD, Study chair, Harvard University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00763867
- Sponsor's protocol ID
- Pro00018007
- Other IDs
- U01HL084904, U01HL084904-01, 521
- Acronym
- RELAX
- Status last verified
- Jul 2013
- First submitted
- 30 Sep 2008
- Last updated
- 23 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E; RELAX Trial. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013 Mar 27;309(12):1268-77. doi: 10.1001/jama.2013.2024.
PubMed 23478662Chiu L, Agrawal V, Armstrong D, Brittain E, Collins S, Hemnes AR, Hill JA, Lindenfeld J, Shah SJ, Stevenson LW, Wang TJ, Gupta DK. Correlates of Plasma NT-proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial. J Am Heart Assoc. 2024 Apr 2;13(7):e031796. doi: 10.1161/JAHA.123.031796. Epub 2024 Mar 27.
PubMed 38533961Bevan GH, Rana M, Al-Furaih N, Dalton J, Zidar DA, Al-Kindi SG. Anisocytosis is associated with myocardial fibrosis and exercise capacity in heart failure with preserved ejection fraction. Heart Lung. 2022 Jul-Aug;54:68-73. doi: 10.1016/j.hrtlng.2022.03.013. Epub 2022 Mar 28.
PubMed 35358904Reddy YNV, Rikhi A, Obokata M, Shah SJ, Lewis GD, AbouEzzedine OF, Dunlay S, McNulty S, Chakraborty H, Stevenson LW, Redfield MM, Borlaug BA. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur J Heart Fail. 2020 Jun;22(6):1009-1018. doi: 10.1002/ejhf.1788. Epub 2020 Mar 9.
PubMed 32150314Fudim M, Kelly JP, Jones AD, AbouEzzeddine OF, Ambrosy AP, Greene SJ, Reddy YNV, Anstrom KJ, Alhanti B, Lewis GD, Hernandez AF, Felker GM. Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure? Am Heart J. 2020 Feb;220:97-107. doi: 10.1016/j.ahj.2019.11.006. Epub 2019 Nov 16.
PubMed 31805424Reddy YNV, Lewis GD, Shah SJ, Obokata M, Abou-Ezzedine OF, Fudim M, Sun JL, Chakraborty H, McNulty S, LeWinter MM, Mann DL, Stevenson LW, Redfield MM, Borlaug BA. Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study. Mayo Clin Proc. 2019 Jul;94(7):1199-1209. doi: 10.1016/j.mayocp.2018.11.037.
PubMed 31272568AbouEzzeddine OF, McKie PM, Dunlay SM, Stevens SR, Felker GM, Borlaug BA, Chen HH, Tracy RP, Braunwald E, Redfield MM. Suppression of Tumorigenicity 2 in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2017 Feb 18;6(2):e004382. doi: 10.1161/JAHA.116.004382.
PubMed 28214792DeVore AD, McNulty S, Alenezi F, Ersboll M, Vader JM, Oh JK, Lin G, Redfield MM, Lewis G, Semigran MJ, Anstrom KJ, Hernandez AF, Velazquez EJ. Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial. Eur J Heart Fail. 2017 Jul;19(7):893-900. doi: 10.1002/ejhf.754. Epub 2017 Feb 14.
PubMed 28194841Hussain I, Mohammed SF, Forfia PR, Lewis GD, Borlaug BA, Gallup DS, Redfield MM. Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial. Circ Heart Fail. 2016 Apr;9(4):e002729. doi: 10.1161/CIRCHEARTFAILURE.115.002729.
PubMed 27072860Lindman BR, Davila-Roman VG, Mann DL, McNulty S, Semigran MJ, Lewis GD, de las Fuentes L, Joseph SM, Vader J, Hernandez AF, Redfield MM. Cardiovascular phenotype in HFpEF patients with or without diabetes: a RELAX trial ancillary study. J Am Coll Cardiol. 2014 Aug 12;64(6):541-9. doi: 10.1016/j.jacc.2014.05.030.
PubMed 25104521Mohammed SF, Borlaug BA, McNulty S, Lewis GD, Lin G, Zakeri R, Semigran MJ, LeWinter M, Hernandez AF, Braunwald E, Redfield MM. Resting ventricular-vascular function and exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study. Circ Heart Fail. 2014 Jul;7(4):580-9. doi: 10.1161/CIRCHEARTFAILURE.114.001192. Epub 2014 May 15.
PubMed 24833648Zakeri R, Borlaug BA, McNulty SE, Mohammed SF, Lewis GD, Semigran MJ, Deswal A, LeWinter M, Hernandez AF, Braunwald E, Redfield MM. Impact of atrial fibrillation on exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study. Circ Heart Fail. 2014 Jan;7(1):123-30. doi: 10.1161/CIRCHEARTFAILURE.113.000568. Epub 2013 Oct 25.
PubMed 24162898Redfield MM, Borlaug BA, Lewis GD, Mohammed SF, Semigran MJ, Lewinter MM, Deswal A, Hernandez AF, Lee KL, Braunwald E; Heart Failure Clinical Research Network. PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial: rationale and design. Circ Heart Fail. 2012 Sep 1;5(5):653-9. doi: 10.1161/CIRCHEARTFAILURE.112.969071.
PubMed 22991405
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX)
- ClinicalTrials.gov ID
- NCT00763867
- Acronym / sponsor ID
- RELAX / Pro00018007
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Diastolic, Decompensated Heart Failure, Sildenafil, Exercise Capacity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Pfizer
- Study start
- Sep 2008
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 1 Oct 2008 (estimated)
- Results
- Posted 3 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks |
| Sildenafil | Experimental | Drug: SildenafilSildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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%
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: Sugar pill to mimic Sildenafil | Drug | Placebo |
| SildenafilAlso: Active Sildenafil | Drug | Sildenafil |
Primary outcome
Exercise Capacity, as Determined by Peak Oxygen Uptake
Time frame: Change from Baseline to Week 24
10 secondary outcomes
Exercise Capacity, as Determined by Peak Oxygen Uptake
Time frame: Change from Baseline to Week 12
Exercise Capacity as Determined by Walk Distance
Time frame: Change from Baseline to Week 12
Composite Score Reflective of Clinical Status
Time frame: Measured at Week 24
Exercise Capacity as Determined by Walk Distance
Time frame: Change from Baseline to Week 24
Cardiopulmonary Exercise Test (CPET) Duration
Time frame: Change from Baseline to Week 12
Cardiopulmonary Exercise Test (CPET) Duration
Time frame: Change from Baseline to Week 24
Ventilatory Anaerobic Threshold
Time frame: Change from Baseline to Week 12
Ventilatory Anaerobic Threshold
Time frame: Change from Baseline to Week 24
Minnesota Living With Heart Failure Questionnaire (MLWHFQ)
Time frame: Change from Baseline to Week 12
Minnesota Living With Heart Failure Questionnaire
Time frame: Change from Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23478662Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E; RELAX Trial. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013 Mar 27;309(12):1268-77. doi: 10.1001/jama.2013.2024.
- Derived from this study: PubMed 38533961Chiu L, Agrawal V, Armstrong D, Brittain E, Collins S, Hemnes AR, Hill JA, Lindenfeld J, Shah SJ, Stevenson LW, Wang TJ, Gupta DK. Correlates of Plasma NT-proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial. J Am Heart Assoc. 2024 Apr 2;13(7):e031796. doi: 10.1161/JAHA.123.031796. Epub 2024 Mar 27.
- Derived from this study: PubMed 35358904Bevan GH, Rana M, Al-Furaih N, Dalton J, Zidar DA, Al-Kindi SG. Anisocytosis is associated with myocardial fibrosis and exercise capacity in heart failure with preserved ejection fraction. Heart Lung. 2022 Jul-Aug;54:68-73. doi: 10.1016/j.hrtlng.2022.03.013. Epub 2022 Mar 28.
- Derived from this study: PubMed 32150314Reddy YNV, Rikhi A, Obokata M, Shah SJ, Lewis GD, AbouEzzedine OF, Dunlay S, McNulty S, Chakraborty H, Stevenson LW, Redfield MM, Borlaug BA. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur J Heart Fail. 2020 Jun;22(6):1009-1018. doi: 10.1002/ejhf.1788. Epub 2020 Mar 9.
- Derived from this study: PubMed 31805424Fudim M, Kelly JP, Jones AD, AbouEzzeddine OF, Ambrosy AP, Greene SJ, Reddy YNV, Anstrom KJ, Alhanti B, Lewis GD, Hernandez AF, Felker GM. Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure? Am Heart J. 2020 Feb;220:97-107. doi: 10.1016/j.ahj.2019.11.006. Epub 2019 Nov 16.
- Derived from this study: PubMed 31272568Reddy YNV, Lewis GD, Shah SJ, Obokata M, Abou-Ezzedine OF, Fudim M, Sun JL, Chakraborty H, McNulty S, LeWinter MM, Mann DL, Stevenson LW, Redfield MM, Borlaug BA. Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study. Mayo Clin Proc. 2019 Jul;94(7):1199-1209. doi: 10.1016/j.mayocp.2018.11.037.
- Derived from this study: PubMed 28214792AbouEzzeddine OF, McKie PM, Dunlay SM, Stevens SR, Felker GM, Borlaug BA, Chen HH, Tracy RP, Braunwald E, Redfield MM. Suppression of Tumorigenicity 2 in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2017 Feb 18;6(2):e004382. doi: 10.1161/JAHA.116.004382.
- Derived from this study: PubMed 28194841DeVore AD, McNulty S, Alenezi F, Ersboll M, Vader JM, Oh JK, Lin G, Redfield MM, Lewis G, Semigran MJ, Anstrom KJ, Hernandez AF, Velazquez EJ. Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial. Eur J Heart Fail. 2017 Jul;19(7):893-900. doi: 10.1002/ejhf.754. Epub 2017 Feb 14.
- Derived from this study: PubMed 27072860Hussain I, Mohammed SF, Forfia PR, Lewis GD, Borlaug BA, Gallup DS, Redfield MM. Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial. Circ Heart Fail. 2016 Apr;9(4):e002729. doi: 10.1161/CIRCHEARTFAILURE.115.002729.
- Derived from this study: PubMed 25104521Lindman BR, Davila-Roman VG, Mann DL, McNulty S, Semigran MJ, Lewis GD, de las Fuentes L, Joseph SM, Vader J, Hernandez AF, Redfield MM. Cardiovascular phenotype in HFpEF patients with or without diabetes: a RELAX trial ancillary study. J Am Coll Cardiol. 2014 Aug 12;64(6):541-9. doi: 10.1016/j.jacc.2014.05.030.
- Derived from this study: PubMed 24833648Mohammed SF, Borlaug BA, McNulty S, Lewis GD, Lin G, Zakeri R, Semigran MJ, LeWinter M, Hernandez AF, Braunwald E, Redfield MM. Resting ventricular-vascular function and exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study. Circ Heart Fail. 2014 Jul;7(4):580-9. doi: 10.1161/CIRCHEARTFAILURE.114.001192. Epub 2014 May 15.
- Derived from this study: PubMed 24162898Zakeri R, Borlaug BA, McNulty SE, Mohammed SF, Lewis GD, Semigran MJ, Deswal A, LeWinter M, Hernandez AF, Braunwald E, Redfield MM. Impact of atrial fibrillation on exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study. Circ Heart Fail. 2014 Jan;7(1):123-30. doi: 10.1161/CIRCHEARTFAILURE.113.000568. Epub 2013 Oct 25.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kerry L. Lee, PhD principal investigator
Duke Clinical Research Institute
Eugene Braunwald, MD study chair
Harvard University
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sildenafil in people with Heart Failure, run by Duke University at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exercise Capacity, as Determined by Peak Oxygen Uptake (time frame: Change from Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00763867, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2014.