CompletedNCT00763867RELAXUpdated Jul 23, 2014Results posted

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

A Phase 3 interventional study of Placebo and Sildenafil in Heart Failure, sponsored by Duke University. Completed at 10 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-07-23.

Sponsored by Duke University · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 216
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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. 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 studied

Heart Failure

Browse trials for

Keywords

Heart Failure, Diastolic
Decompensated Heart Failure
Sildenafil
Exercise Capacity

In context

Heart Failure

5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.

This study's enrollment of 216 is above the median of 72 across 3,736 interventional studies indexed under Heart Failure.

Browse Heart Failure studies →

Lead sponsor

Duke University is the lead sponsor of 2,025 studies on the registry; 275 are open to participants now.

Of its 194 completed or terminated interventional studies of FDA-regulated products, 159 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 216 participants (actual)

Study arms

Placebo comparator
Placebo
Placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Drug: Placebo
Experimental
Sildenafil
Sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Drug: Sildenafil

Interventions

DrugPlacebo
Also known as: Sugar pill to mimic Sildenafil
DrugSildenafil
Also known as: Active Sildenafil

What researchers measure

Primary outcomes

Exercise Capacity, as Determined by Peak Oxygen Uptake
Time frame: Change from Baseline to Week 24

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
6 Minute Walk Distance
Time frame: 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: 1. Death (lowest tier) The person with the shortest time from randomization to death is given the lowest rank within the tier. 2. 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. 3. 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)
Time frame: Measured at Week 24
Exercise Capacity as Determined by Walk Distance
6 minute walk distance
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Change from Baseline to Week 24

Other outcomes

MRI Left Ventricular Mass
A decrease in LV Mass is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Left Ventricular Mass Index
A decrease in Left Ventricular Mass Index is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Left Ventricular End Diastolic Volume
An increase in Left Ventricular End Diastolic Volume is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Left Ventricular End Diastolic Volume Index
An increase in Left Ventricular End Diastolic Volume Index is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Left Ventricular End Systolic Volume Index
An increase in Left Ventricular End Systolic Volume Index is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Left Ventricular Ejection Fraction (LVEF)
An increase in LVEF is considered an improvement
Time frame: Change from Baseline to Week 24
Echocardiogram Left Ventricular Mass
A decrease in Left Ventricular Mass is considered an improvement
Time frame: Change from Baseline to Week 24
Medial Diastolic Elastance
A decrease in Medial Diastolic Elastance is considered an improvement
Time frame: Change from Baseline to Week 24
Lateral Diastolic Elastance
A decrease in Lateral Diastolic Elastance is considered an improvement
Time frame: Change from Baseline to Week 24
Medial Left Ventricular Relaxation
An increase in Left Ventricular relaxation is considered to be an improvement
Time frame: Change from Baseline to Week 24
Lateral Left Ventricular Relaxation
An increase in Left Ventricular relaxation is considered to be an improvement
Time frame: Change from Baseline to Week 24
Medial Filling Pressure
A decrease in medial filling pressure is considered an improvement
Time frame: Change from Baseline to Week 24
Lateral Filling Pressure
A decrease in lateral filling pressure is considered an improvement
Time frame: Change from Baseline to Week 24
ECHO Effective Arterial Elastance
A decrease in Effective Arterial Elastance is considered an improvement
Time frame: Change from Baseline to Week 24
ECHO Systemic Vascular Resistance
A decrease in Systemic Vascular Resistance is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Effective Arterial Elastance
A decrease in Effective Arterial Elastance is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Systemic Vascular Resistance
A decrease in Systemic Vascular Resistance is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Aortic Thickness
A decrease in Aortic Thickness is considered an improvement
Time frame: Change from Baseline to Week 24
MRI Aortic Distensibility
An increase in Aortic Distensibility is considered to be an improvement
Time frame: Change from Baseline to Week 24
ECHO Pulmonary Artery Systolic Pressure
A decrease in Pulmonary Artery Systolic Pressure is considered to be an improvement
Time frame: Change from Baseline to Week 24
Best Available Creatinine
Best available=local lab results only when core lab results not available
Time frame: Change from Baseline to Week 24
Best Available Glomerular Filtration Rate (GFR)
Best available=local lab results when core lab results not available
Time frame: Change from Baseline to Week 24
Cystatin C
Time frame: Change from Baseline to Week 24
Uric Acid
Time frame: Change from Baseline to Week 24
N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)
Time frame: Change from Baseline to Week 24
Aldosterone
Time frame: Change from Baseline to Week 24
High Sensitivity Troponin I
Time frame: Change from Baseline to Week 24
Procollagen III N-terminal Peptide
Time frame: Change from Baseline to Week 24
Endothelin-1
Time frame: Change from Baseline to Week 24
High Sensitivity C-Reactive Protein
Time frame: Change from Baseline to Week 24
Collagen Type I (CITP)
Time frame: Change from Baseline to Week 24
Cyclic Guanosine Monophosphate (cGMP)
Time frame: Change from Baseline to Week 24
Galectin 3
Time frame: Change from Baseline to Week 24
Furosemide-Equivalent Dose
Time frame: Change from Baseline to Week 24

Results

Posted Jul 3, 2013

Participant flow

Participant flow — Overall Study
Milestone	Placebo	Sildenafil
Started	103	113
Completed	98	101
Not completed	5	12

Outcome measures

PrimaryExercise Capacity, as Determined by Peak Oxygen Uptake

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · ml/min/kg

Exercise Capacity, as Determined by Peak Oxygen Uptake
ml/min/kg	Placebo	Sildenafil
Exercise Capacity, as Determined by Peak Oxygen Uptake	-0.07 ± 2.00	-0.12 ± 2.29

SecondaryExercise Capacity, as Determined by Peak Oxygen Uptake

Time frame:: Change from Baseline to Week 12
Reported as:: Mean · ml/min/kg

Exercise Capacity, as Determined by Peak Oxygen Uptake
ml/min/kg	Placebo	Sildenafil
Exercise Capacity, as Determined by Peak Oxygen Uptake	0.02 ± 1.70	0.03 ± 2.20

SecondaryExercise Capacity as Determined by Walk Distance

6 Minute Walk Distance

Time frame:: Change from Baseline to Week 12
Reported as:: Mean · meters

Exercise Capacity as Determined by Walk Distance
meters	Placebo	Sildenafil
Exercise Capacity as Determined by Walk Distance	26.2 ± 83.7	5.2 ± 69.1

SecondaryComposite Score Reflective of Clinical Status

Participants ranked sequentially with ranking stratified in one of three tiers based on: 1. Death (lowest tier) The person with the shortest time from randomization to death is given the lowest rank within the tier. 2. 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. 3. 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)

Time frame:: Measured at Week 24
Reported as:: Mean · units on a scale

Composite Score Reflective of Clinical Status
units on a scale	Placebo	Sildenafil
Composite Score Reflective of Clinical Status	95.8 ± 55.0	94.2 ± 54.6

SecondaryExercise Capacity as Determined by Walk Distance

6 minute walk distance

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · meters

Exercise Capacity as Determined by Walk Distance
meters	Placebo	Sildenafil
Exercise Capacity as Determined by Walk Distance	17.5 ± 88.6	12.0 ± 94.2

SecondaryCardiopulmonary 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

Time frame:: Change from Baseline to Week 12
Reported as:: Mean · minutes

Cardiopulmonary Exercise Test (CPET) Duration
minutes	Placebo	Sildenafil
Cardiopulmonary Exercise Test (CPET) Duration	0.25 ± 1.61	-0.15 ± 1.60

SecondaryCardiopulmonary 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

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · minutes

Cardiopulmonary Exercise Test (CPET) Duration
minutes	Placebo	Sildenafil
Cardiopulmonary Exercise Test (CPET) Duration	9.82 ± 2.63	9.77 ± 3.21

SecondaryVentilatory 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

Time frame:: Change from Baseline to Week 12
Reported as:: Mean · ml/min/kg

Ventilatory Anaerobic Threshold
ml/min/kg	Placebo	Sildenafil
Ventilatory Anaerobic Threshold	-0.01 ± 1.14	0.06 ± 1.24

SecondaryVentilatory 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

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · ml/min/kg

Ventilatory Anaerobic Threshold
ml/min/kg	Placebo	Sildenafil
Ventilatory Anaerobic Threshold	-0.10 ± 1.26	0.17 ± 1.26

SecondaryMinnesota 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

Time frame:: Change from Baseline to Week 12
Reported as:: Mean · units on a scale

Minnesota Living With Heart Failure Questionnaire (MLWHFQ)
units on a scale	Placebo	Sildenafil
Minnesota Living With Heart Failure Questionnaire (MLWHFQ)	-8.3 ± 22.0	-6.2 ± 20.8

SecondaryMinnesota Living With Heart Failure Questionnaire

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · units on a scale

Minnesota Living With Heart Failure Questionnaire
units on a scale	Placebo	Sildenafil
Minnesota Living With Heart Failure Questionnaire	-9.2 ± 24.2	-8.3 ± 19.7

Other pre-specifiedMRI Left Ventricular Mass

A decrease in LV Mass is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · gm

MRI Left Ventricular Mass
gm	Placebo	Sildenafil
MRI Left Ventricular Mass	0.29 ± 14.43	-0.07 ± 14.93

Other pre-specifiedMRI Left Ventricular Mass Index

A decrease in Left Ventricular Mass Index is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · gm/m^2

MRI Left Ventricular Mass Index
gm/m^2	Placebo	Sildenafil
MRI Left Ventricular Mass Index	0.47 ± 6.54	0.61 ± 6.96

Other pre-specifiedMRI Left Ventricular End Diastolic Volume

An increase in Left Ventricular End Diastolic Volume is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mL

MRI Left Ventricular End Diastolic Volume
mL	Placebo	Sildenafil
MRI Left Ventricular End Diastolic Volume	-3.70 ± 21.03	3.61 ± 25.02

Other pre-specifiedMRI Left Ventricular End Diastolic Volume Index

An increase in Left Ventricular End Diastolic Volume Index is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mL/m^2

MRI Left Ventricular End Diastolic Volume Index
mL/m^2	Placebo	Sildenafil
MRI Left Ventricular End Diastolic Volume Index	-1.73 ± 9.45	2.11 ± 11.21

Other pre-specifiedMRI Left Ventricular End Systolic Volume Index

An increase in Left Ventricular End Systolic Volume Index is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mL/m^2

MRI Left Ventricular End Systolic Volume Index
mL/m^2	Placebo	Sildenafil
MRI Left Ventricular End Systolic Volume Index	-0.82 ± 4.09	0.25 ± 6.12

Other pre-specifiedMRI Left Ventricular Ejection Fraction (LVEF)

An increase in LVEF is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · percentage of volume

MRI Left Ventricular Ejection Fraction (LVEF)
percentage of volume	Placebo	Sildenafil
MRI Left Ventricular Ejection Fraction (LVEF)	0.55 ± 4.28	0.62 ± 4.88

Other pre-specifiedEchocardiogram Left Ventricular Mass

A decrease in Left Ventricular Mass is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · gm

Echocardiogram Left Ventricular Mass
gm	Placebo	Sildenafil
Echocardiogram Left Ventricular Mass	-1.93 ± 47.36	-8.79 ± 35.60

Other pre-specifiedMedial Diastolic Elastance

A decrease in Medial Diastolic Elastance is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · (m/sec)/cc

Medial Diastolic Elastance
(m/sec)/cc	Placebo	Sildenafil
Medial Diastolic Elastance	-0.03 ± 0.11	-0.01 ± 0.10

Other pre-specifiedLateral Diastolic Elastance

A decrease in Lateral Diastolic Elastance is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · (m/sec)/cc

Lateral Diastolic Elastance
(m/sec)/cc	Placebo	Sildenafil
Lateral Diastolic Elastance	-0.00 ± 0.09	-0.01 ± 0.08

Other pre-specifiedMedial Left Ventricular Relaxation

An increase in Left Ventricular relaxation is considered to be an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · m/sec

Medial Left Ventricular Relaxation
m/sec	Placebo	Sildenafil
Medial Left Ventricular Relaxation	0.00 ± 0.02	-0.00 ± 0.02

Other pre-specifiedLateral Left Ventricular Relaxation

An increase in Left Ventricular relaxation is considered to be an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · m/sec

Lateral Left Ventricular Relaxation
m/sec	Placebo	Sildenafil
Lateral Left Ventricular Relaxation	-0.00 ± 0.02	-0.00 ± 0.02

Other pre-specifiedMedial Filling Pressure

A decrease in medial filling pressure is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · m/sec

Medial Filling Pressure
m/sec	Placebo	Sildenafil
Medial Filling Pressure	-1.64 ± 6.83	0.33 ± 6.04

Other pre-specifiedLateral Filling Pressure

A decrease in lateral filling pressure is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · m/sec

Lateral Filling Pressure
m/sec	Placebo	Sildenafil
Lateral Filling Pressure	-0.44 ± 5.17	-0.04 ± 5.68

Other pre-specifiedECHO Effective Arterial Elastance

A decrease in Effective Arterial Elastance is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · Farads-1

ECHO Effective Arterial Elastance
Farads-1	Placebo	Sildenafil
ECHO Effective Arterial Elastance	0.03 ± 0.46	-0.07 ± 0.36

Other pre-specifiedECHO Systemic Vascular Resistance

A decrease in Systemic Vascular Resistance is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · Woods units

ECHO Systemic Vascular Resistance
Woods units	Placebo	Sildenafil
ECHO Systemic Vascular Resistance	0.01 ± 0.46	-0.01 ± 0.35

Other pre-specifiedMRI Effective Arterial Elastance

A decrease in Effective Arterial Elastance is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · Farads-1

MRI Effective Arterial Elastance
Farads-1	Placebo	Sildenafil
MRI Effective Arterial Elastance	0.04 ± 0.44	-0.15 ± 0.38

Other pre-specifiedMRI Systemic Vascular Resistance

A decrease in Systemic Vascular Resistance is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · Woods units

MRI Systemic Vascular Resistance
Woods units	Placebo	Sildenafil
MRI Systemic Vascular Resistance	0.06 ± 0.57	-0.10 ± 0.39

Other pre-specifiedMRI Aortic Thickness

A decrease in Aortic Thickness is considered an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mm

MRI Aortic Thickness
mm	Placebo	Sildenafil
MRI Aortic Thickness	0.01 ± 0.17	-0.03 ± 0.18

Other pre-specifiedMRI Aortic Distensibility

An increase in Aortic Distensibility is considered to be an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · cm^2*dyne-1

MRI Aortic Distensibility
cm^2*dyne-1	Placebo	Sildenafil
MRI Aortic Distensibility	0.12 ± 0.66	0.29 ± 1.13

Other pre-specifiedECHO Pulmonary Artery Systolic Pressure

A decrease in Pulmonary Artery Systolic Pressure is considered to be an improvement

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mmHg

ECHO Pulmonary Artery Systolic Pressure
mmHg	Placebo	Sildenafil
ECHO Pulmonary Artery Systolic Pressure	-0.15 ± 12.43	0.32 ± 10.09

Other pre-specifiedBest Available Creatinine

Best available=local lab results only when core lab results not available

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mg/dL

Best Available Creatinine
mg/dL	Placebo	Sildenafil
Best Available Creatinine	0.02 ± 0.23	0.09 ± 0.29

Other pre-specifiedBest Available Glomerular Filtration Rate (GFR)

Best available=local lab results when core lab results not available

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mL/min/1.73m^2

Best Available Glomerular Filtration Rate (GFR)
mL/min/1.73m^2	Placebo	Sildenafil
Best Available Glomerular Filtration Rate (GFR)	-0.91 ± 15.02	-3.27 ± 12.16

Other pre-specifiedCystatin C

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mg/L

Cystatin C
mg/L	Placebo	Sildenafil
Cystatin C	-0.01 ± 0.27	0.10 ± 0.29

Other pre-specifiedUric Acid

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mg/dL

Uric Acid
mg/dL	Placebo	Sildenafil
Uric Acid	-0.11 ± 1.79	0.51 ± 1.80

Other pre-specifiedN-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · pg/mL

N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)
pg/mL	Placebo	Sildenafil
N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	-50.52 ± 799.87	158.25 ± 538.85

Other pre-specifiedAldosterone

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · pg/mL

Aldosterone
pg/mL	Placebo	Sildenafil
Aldosterone	7.04 ± 220.06	1.22 ± 213.47

Other pre-specifiedHigh Sensitivity Troponin I

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · pg/mL

High Sensitivity Troponin I
pg/mL	Placebo	Sildenafil
High Sensitivity Troponin I	3.88 ± 29.71	11.11 ± 62.49

Other pre-specifiedProcollagen III N-terminal Peptide

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · ug/L

Procollagen III N-terminal Peptide
ug/L	Placebo	Sildenafil
Procollagen III N-terminal Peptide	0.58 ± 5.22	0.41 ± 3.90

Other pre-specifiedEndothelin-1

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · pg/mL

Endothelin-1
pg/mL	Placebo	Sildenafil
Endothelin-1	0.04 ± 1.51	0.49 ± 1.29

Other pre-specifiedHigh Sensitivity C-Reactive Protein

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mg/L

High Sensitivity C-Reactive Protein
mg/L	Placebo	Sildenafil
High Sensitivity C-Reactive Protein	0.36 ± 7.20	0.32 ± 5.49

Other pre-specifiedCollagen Type I (CITP)

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · ug/L

Collagen Type I (CITP)
ug/L	Placebo	Sildenafil
Collagen Type I (CITP)	-0.17 ± 4.03	5.61 ± 48.96

Other pre-specifiedCyclic Guanosine Monophosphate (cGMP)

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · pmol/mL

Cyclic Guanosine Monophosphate (cGMP)
pmol/mL	Placebo	Sildenafil
Cyclic Guanosine Monophosphate (cGMP)	1.28 ± 37.05	8.72 ± 30.22

Other pre-specifiedGalectin 3

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · ng/mL

Galectin 3
ng/mL	Placebo	Sildenafil
Galectin 3	1.10 ± 9.63	1.26 ± 7.71

Other pre-specifiedFurosemide-Equivalent Dose

Time frame:: Change from Baseline to Week 24
Reported as:: Mean · mg

Furosemide-Equivalent Dose
mg	Placebo	Sildenafil
Furosemide-Equivalent Dose	-0.23 ± 35.44	7.27 ± 59.53

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo	—	16/103 (15.5%)	72/103 (69.9%)
Sildenafil	—	25/113 (22.1%)	83/113 (73.5%)

Most frequent serious events

Showing 10 of 18

Most frequent serious events
Event	Placebo	Sildenafil
Cardiac FailureCardiac disorders	7/103	9/113
PneumoniaInfections and infestations	1/103	4/113
Cardiac Failure AcuteCardiac disorders	3/103	2/113
Atrial FibrillationCardiac disorders	2/103	1/113
HypertensionVascular disorders	2/103	0/113
Acute Myocardial InfarctionCardiac disorders	1/103	1/113
Angina PectorisCardiac disorders	1/103	0/113
Angina UnstableCardiac disorders	1/103	1/113
Hypertensive EmergencyVascular disorders	1/103	0/113
Atrioventricular Block Second DegreeCardiac disorders	0/103	1/113

Most frequent other events

Showing 10 of 30

Most frequent other events
Event	Placebo	Sildenafil
HeadacheNervous system disorders	16/103	27/113
DiarheaGastrointestinal disorders	14/103	14/113
DizzinessNervous system disorders	11/103	9/113
FlushingVascular disorders	3/103	9/113
HypotensionVascular disorders	1/103	8/113
Visual ImpairmentEye disorders	5/103	7/113
Cardiac FailureCardiac disorders	1/103	5/113
PalpitationsCardiac disorders	4/103	5/113
Atrial FibrillationCardiac disorders	4/103	0/113
TinnitisEar and labyrinth disorders	4/103	3/113

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Placebo	Sildenafil	Total
<=18 years	0	0	0
Between 18 and 65 years	42	38	80
>=65 years	61	75	136

Age, Continuous
Age, Continuous(years)	Placebo	Sildenafil	Total
Mean	68.7 ± 10.1	68.4 ± 10.5	68.5 ± 10.3

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	Sildenafil	Total
Female	55	49	104
Male	48	64	112

Region of Enrollment
Region of Enrollment(participants)	Placebo	Sildenafil	Total
United States	93	101	194
Canada	10	12	22

Study locations

10 sites

Mayo Clinic Arizona
Phoenix, Arizona 85054, United States
Morehouse School of Medicine
Atlanta, Georgia 30310, United States
Brigham and Women's Hospital
Boston, Massachusetts 02115, United States
Minnesota Heart Failure Network
Minneapolis, Minnesota 55415, United States
Mayo Clinic
Rochester, Minnesota 55905, United States
Duke University Medical Center
Durham, North Carolina 27705, United States
Baylor College of Medicine
Houston, Texas 77030, United States
University of Utah Health Sciences Center
Murray, Utah 84107, United States
University of Vermont - Fletcher Allen Health Care
Burlington, Vermont 05401, United States
Montreal Heart Institute
Montreal, Quebec H1T - 1C8, Canada

References and documents

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 23478662 ↗
Bevan 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 35358904 ↗
Reddy 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 32150314 ↗
Fudim 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 31805424 ↗
Reddy 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 31272568 ↗
AbouEzzeddine 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. Erratum In: J Am Heart Assoc. 2017 Sep 20;6(9):e002231. doi: 10.1161/JAHA.117.002231. PubMed 28214792 ↗
DeVore 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 28194841 ↗
Hussain 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 27072860 ↗
Lindman 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 25104521 ↗
Mohammed 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 24833648 ↗
Zakeri 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 24162898 ↗
Redfield 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 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 23, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00763867
Lead sponsor: Duke University
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Pfizer
Responsible party: Sponsor
First posted: Oct 1, 2008
Start date: Sep 2008
Primary completion: Sep 2012
Completion: Sep 2012
Results posted: Jul 3, 2013
Last update: Jul 23, 2014

Study contacts

Kerry L. Lee, PhD

principal investigator · Duke Clinical Research Institute

Eugene Braunwald, MD

study chair · Harvard University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2013. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Heart Failure→

Other studies from this sponsor

Duke University

Start the discussion