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

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ClinicalTrials.gov Identifier: NCT00763867
Recruitment Status : Completed
First Posted : October 1, 2008
Results First Posted : July 3, 2013
Last Update Posted : July 23, 2014
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Pfizer
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Placebo
Drug: Sildenafil
Enrollment 216

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Period Title: Overall Study
Started 103 113
Completed 98 101
Not Completed 5 12
Arm/Group Title Placebo Sildenafil Total
Hide Arm/Group Description 20 mg tid for 12 weeks followed by 60 mg tid for 12 weeks 20 mg tid for 12 weeks followed by 60 mg tid for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 103 113 216
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants 113 participants 216 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
42
  40.8%
38
  33.6%
80
  37.0%
>=65 years
61
  59.2%
75
  66.4%
136
  63.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants 113 participants 216 participants
68.7  (10.1) 68.4  (10.5) 68.5  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants 113 participants 216 participants
Female
55
  53.4%
49
  43.4%
104
  48.1%
Male
48
  46.6%
64
  56.6%
112
  51.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 113 participants 216 participants
United States 93 101 194
Canada 10 12 22
1.Primary Outcome
Title Exercise Capacity, as Determined by Peak Oxygen Uptake
Hide Description [Not Specified]
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 94 91
Mean (Standard Deviation)
Unit of Measure: ml/min/kg
-0.07  (2.00) -0.12  (2.29)
2.Secondary Outcome
Title Exercise Capacity, as Determined by Peak Oxygen Uptake
Hide Description [Not Specified]
Time Frame Change from Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 96 97
Mean (Standard Deviation)
Unit of Measure: ml/min/kg
0.02  (1.70) 0.03  (2.20)
3.Secondary Outcome
Title Exercise Capacity as Determined by Walk Distance
Hide Description 6 Minute Walk Distance
Time Frame Change from Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 96 99
Mean (Standard Deviation)
Unit of Measure: meters
26.2  (83.7) 5.2  (69.1)
4.Secondary Outcome
Title Composite Score Reflective of Clinical Status
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 94 95
Mean (Standard Deviation)
Unit of Measure: units on a scale
95.8  (55.0) 94.2  (54.6)
5.Secondary Outcome
Title Exercise Capacity as Determined by Walk Distance
Hide Description 6 minute walk distance
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 90
Mean (Standard Deviation)
Unit of Measure: meters
17.5  (88.6) 12.0  (94.2)
6.Secondary Outcome
Title Cardiopulmonary Exercise Test (CPET) Duration
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 91 88
Mean (Standard Deviation)
Unit of Measure: minutes
0.25  (1.61) -0.15  (1.60)
7.Secondary Outcome
Title Cardiopulmonary Exercise Test (CPET) Duration
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 89 86
Mean (Standard Deviation)
Unit of Measure: minutes
9.82  (2.63) 9.77  (3.21)
8.Secondary Outcome
Title Ventilatory Anaerobic Threshold
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 96 92
Mean (Standard Deviation)
Unit of Measure: ml/min/kg
-0.01  (1.14) 0.06  (1.24)
9.Secondary Outcome
Title Ventilatory Anaerobic Threshold
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 94 88
Mean (Standard Deviation)
Unit of Measure: ml/min/kg
-0.10  (1.26) 0.17  (1.26)
10.Secondary Outcome
Title Minnesota Living With Heart Failure Questionnaire (MLWHFQ)
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 97 95
Mean (Standard Deviation)
Unit of Measure: units on a scale
-8.3  (22.0) -6.2  (20.8)
11.Secondary Outcome
Title Minnesota Living With Heart Failure Questionnaire
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 91 91
Mean (Standard Deviation)
Unit of Measure: units on a scale
-9.2  (24.2) -8.3  (19.7)
12.Other Pre-specified Outcome
Title MRI Left Ventricular Mass
Hide Description A decrease in LV Mass is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 47 49
Mean (Standard Deviation)
Unit of Measure: gm
0.29  (14.43) -0.07  (14.93)
13.Other Pre-specified Outcome
Title MRI Left Ventricular Mass Index
Hide Description A decrease in Left Ventricular Mass Index is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 47 49
Mean (Standard Deviation)
Unit of Measure: gm/m^2
0.47  (6.54) 0.61  (6.96)
14.Other Pre-specified Outcome
Title MRI Left Ventricular End Diastolic Volume
Hide Description An increase in Left Ventricular End Diastolic Volume is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 103 113
Mean (Standard Deviation)
Unit of Measure: mL
-3.70  (21.03) 3.61  (25.02)
15.Other Pre-specified Outcome
Title MRI Left Ventricular End Diastolic Volume Index
Hide Description An increase in Left Ventricular End Diastolic Volume Index is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 47 49
Mean (Standard Deviation)
Unit of Measure: mL/m^2
-1.73  (9.45) 2.11  (11.21)
16.Other Pre-specified Outcome
Title MRI Left Ventricular End Systolic Volume Index
Hide Description An increase in Left Ventricular End Systolic Volume Index is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 47 49
Mean (Standard Deviation)
Unit of Measure: mL/m^2
-0.82  (4.09) 0.25  (6.12)
17.Other Pre-specified Outcome
Title MRI Left Ventricular Ejection Fraction (LVEF)
Hide Description An increase in LVEF is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 47 49
Mean (Standard Deviation)
Unit of Measure: percentage of volume
0.55  (4.28) 0.62  (4.88)
18.Other Pre-specified Outcome
Title Echocardiogram Left Ventricular Mass
Hide Description A decrease in Left Ventricular Mass is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 56 58
Mean (Standard Deviation)
Unit of Measure: gm
-1.93  (47.36) -8.79  (35.60)
19.Other Pre-specified Outcome
Title Medial Diastolic Elastance
Hide Description A decrease in Medial Diastolic Elastance is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 72 68
Mean (Standard Deviation)
Unit of Measure: (m/sec)/cc
-0.03  (0.11) -0.01  (0.10)
20.Other Pre-specified Outcome
Title Lateral Diastolic Elastance
Hide Description A decrease in Lateral Diastolic Elastance is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 67 67
Mean (Standard Deviation)
Unit of Measure: (m/sec)/cc
-0.00  (0.09) -0.01  (0.08)
21.Other Pre-specified Outcome
Title Medial Left Ventricular Relaxation
Hide Description An increase in Left Ventricular relaxation is considered to be an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 83 77
Mean (Standard Deviation)
Unit of Measure: m/sec
0.00  (0.02) -0.00  (0.02)
22.Other Pre-specified Outcome
Title Lateral Left Ventricular Relaxation
Hide Description An increase in Left Ventricular relaxation is considered to be an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 78 74
Mean (Standard Deviation)
Unit of Measure: m/sec
-0.00  (0.02) -0.00  (0.02)
23.Other Pre-specified Outcome
Title Medial Filling Pressure
Hide Description A decrease in medial filling pressure is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 80 75
Mean (Standard Deviation)
Unit of Measure: m/sec
-1.64  (6.83) 0.33  (6.04)
24.Other Pre-specified Outcome
Title Lateral Filling Pressure
Hide Description A decrease in lateral filling pressure is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 75 72
Mean (Standard Deviation)
Unit of Measure: m/sec
-0.44  (5.17) -0.04  (5.68)
25.Other Pre-specified Outcome
Title ECHO Effective Arterial Elastance
Hide Description A decrease in Effective Arterial Elastance is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 76 68
Mean (Standard Deviation)
Unit of Measure: Farads-1
0.03  (0.46) -0.07  (0.36)
26.Other Pre-specified Outcome
Title ECHO Systemic Vascular Resistance
Hide Description A decrease in Systemic Vascular Resistance is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 74 66
Mean (Standard Deviation)
Unit of Measure: Woods units
0.01  (0.46) -0.01  (0.35)
27.Other Pre-specified Outcome
Title MRI Effective Arterial Elastance
Hide Description A decrease in Effective Arterial Elastance is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 45 47
Mean (Standard Deviation)
Unit of Measure: Farads-1
0.04  (0.44) -0.15  (0.38)
28.Other Pre-specified Outcome
Title MRI Systemic Vascular Resistance
Hide Description A decrease in Systemic Vascular Resistance is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 45 47
Mean (Standard Deviation)
Unit of Measure: Woods units
0.06  (0.57) -0.10  (0.39)
29.Other Pre-specified Outcome
Title MRI Aortic Thickness
Hide Description A decrease in Aortic Thickness is considered an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 33 31
Mean (Standard Deviation)
Unit of Measure: mm
0.01  (0.17) -0.03  (0.18)
30.Other Pre-specified Outcome
Title MRI Aortic Distensibility
Hide Description An increase in Aortic Distensibility is considered to be an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 31 29
Mean (Standard Deviation)
Unit of Measure: cm^2*dyne-1
0.12  (0.66) 0.29  (1.13)
31.Other Pre-specified Outcome
Title ECHO Pulmonary Artery Systolic Pressure
Hide Description A decrease in Pulmonary Artery Systolic Pressure is considered to be an improvement
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 58 45
Mean (Standard Deviation)
Unit of Measure: mmHg
-0.15  (12.43) 0.32  (10.09)
32.Other Pre-specified Outcome
Title Best Available Creatinine
Hide Description Best available=local lab results only when core lab results not available
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 98 100
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.02  (0.23) 0.09  (0.29)
33.Other Pre-specified Outcome
Title Best Available Glomerular Filtration Rate (GFR)
Hide Description Best available=local lab results when core lab results not available
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 98 100
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
-0.91  (15.02) -3.27  (12.16)
34.Other Pre-specified Outcome
Title Cystatin C
Hide Description [Not Specified]
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 95
Mean (Standard Deviation)
Unit of Measure: mg/L
-0.01  (0.27) 0.10  (0.29)
35.Other Pre-specified Outcome
Title Uric Acid
Hide Description [Not Specified]
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description:
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 94 94
Mean (Standard Deviation)
Unit of Measure: mg/dL
-0.11  (1.79) 0.51  (1.80)
36.Other Pre-specified Outcome
Title N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)
Hide Description [Not Specified]
Time Frame Change from Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 94 95
Mean (Standard Deviation)
Unit of Measure: pg/mL
-50.52  (799.87) 158.25  (538.85)
37.Other Pre-specified Outcome
Title Aldosterone
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 95
Mean (Standard Deviation)
Unit of Measure: pg/mL
7.04  (220.06) 1.22  (213.47)
38.Other Pre-specified Outcome
Title High Sensitivity Troponin I
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 93
Mean (Standard Deviation)
Unit of Measure: pg/mL
3.88  (29.71) 11.11  (62.49)
39.Other Pre-specified Outcome
Title Procollagen III N-terminal Peptide
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 93 95
Mean (Standard Deviation)
Unit of Measure: ug/L
0.58  (5.22) 0.41  (3.90)
40.Other Pre-specified Outcome
Title Endothelin-1
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 95
Mean (Standard Deviation)
Unit of Measure: pg/mL
0.04  (1.51) 0.49  (1.29)
41.Other Pre-specified Outcome
Title High Sensitivity C-Reactive Protein
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 95
Mean (Standard Deviation)
Unit of Measure: mg/L
0.36  (7.20) 0.32  (5.49)
42.Other Pre-specified Outcome
Title Collagen Type I (CITP)
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 95
Mean (Standard Deviation)
Unit of Measure: ug/L
-0.17  (4.03) 5.61  (48.96)
43.Other Pre-specified Outcome
Title Cyclic Guanosine Monophosphate (cGMP)
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 95 95
Mean (Standard Deviation)
Unit of Measure: pmol/mL
1.28  (37.05) 8.72  (30.22)
44.Other Pre-specified Outcome
Title Galectin 3
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 93 92
Mean (Standard Deviation)
Unit of Measure: ng/mL
1.10  (9.63) 1.26  (7.71)
45.Other Pre-specified Outcome
Title Furosemide-Equivalent Dose
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Time Frame Change from Baseline to Week 24
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Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Arm/Group Title Placebo Sildenafil
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placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
Overall Number of Participants Analyzed 98 100
Mean (Standard Deviation)
Unit of Measure: mg
-0.23  (35.44) 7.27  (59.53)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Sildenafil
Hide Arm/Group Description placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
All-Cause Mortality
Placebo Sildenafil
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Sildenafil
Affected / at Risk (%) Affected / at Risk (%)
Total   16/103 (15.53%)   25/113 (22.12%) 
Cardiac disorders     
Acute Myocardial Infarction  1/103 (0.97%)  1/113 (0.88%) 
Angina Pectoris  1/103 (0.97%)  0/113 (0.00%) 
Angina Unstable  1/103 (0.97%)  1/113 (0.88%) 
Atrial Fibrillation  2/103 (1.94%)  1/113 (0.88%) 
Atrioventricular Block Second Degree  0/103 (0.00%)  1/113 (0.88%) 
Bradycardia  0/103 (0.00%)  1/113 (0.88%) 
Cardiac Failure  7/103 (6.80%)  9/113 (7.96%) 
Cardiac Failure Acute  3/103 (2.91%)  2/113 (1.77%) 
Palpitations  0/103 (0.00%)  1/113 (0.88%) 
Sinus Bradycardia  0/103 (0.00%)  1/113 (0.88%) 
Supraventricular Tachycardia  0/103 (0.00%)  1/113 (0.88%) 
Ventricular Tachycardia  0/103 (0.00%)  1/113 (0.88%) 
Infections and infestations     
Implant Site Infection  0/103 (0.00%)  1/113 (0.88%) 
Pneumonia  1/103 (0.97%)  4/113 (3.54%) 
Pyelonephritis  0/103 (0.00%)  1/113 (0.88%) 
Vascular disorders     
Hypertension  2/103 (1.94%)  0/113 (0.00%) 
Hypertensive Emergency  1/103 (0.97%)  0/113 (0.00%) 
Hypotension  0/103 (0.00%)  1/113 (0.88%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Sildenafil
Affected / at Risk (%) Affected / at Risk (%)
Total   72/103 (69.90%)   83/113 (73.45%) 
Cardiac disorders     
Angina Pectoris  2/103 (1.94%)  0/113 (0.00%) 
Atrial Fibrillation  4/103 (3.88%)  0/113 (0.00%) 
Atrial Flutter  1/103 (0.97%)  1/113 (0.88%) 
Atrioventricular Block Second Degree  1/103 (0.97%)  0/113 (0.00%) 
Cardiac Failure  1/103 (0.97%)  5/113 (4.42%) 
Palpitations  4/103 (3.88%)  5/113 (4.42%) 
Sinus Tachycardia  0/103 (0.00%)  1/113 (0.88%) 
Ear and labyrinth disorders     
Tinnitis  4/103 (3.88%)  3/113 (2.65%) 
Eye disorders     
Visual Impairment  5/103 (4.85%)  7/113 (6.19%) 
Gastrointestinal disorders     
Diarhea  14/103 (13.59%)  14/113 (12.39%) 
General disorders     
Non-Cardiac Chest Pain  4/103 (3.88%)  0/113 (0.00%) 
Nervous system disorders     
Balance Disorder  0/103 (0.00%)  1/113 (0.88%) 
Dizziness  11/103 (10.68%)  9/113 (7.96%) 
Dizziness Postural  1/103 (0.97%)  0/113 (0.00%) 
Dysgeusia  0/103 (0.00%)  1/113 (0.88%) 
Headache  16/103 (15.53%)  27/113 (23.89%) 
Memory Impairment  0/103 (0.00%)  1/113 (0.88%) 
Parosmia  0/103 (0.00%)  1/113 (0.88%) 
Presyncope  0/103 (0.00%)  2/113 (1.77%) 
Syncope  2/103 (1.94%)  0/113 (0.00%) 
Tremor  0/103 (0.00%)  1/113 (0.88%) 
Vascular disorders     
Flushing  3/103 (2.91%)  9/113 (7.96%) 
Hot Flush  0/103 (0.00%)  2/113 (1.77%) 
Hypertension  1/103 (0.97%)  0/113 (0.00%) 
Hypotension  0/103 (0.00%)  1/113 (0.88%) 
Hypotension  1/103 (0.97%)  8/113 (7.08%) 
Perhipheral Coldness  0/103 (0.00%)  1/113 (0.88%) 
Peripheral Ischaemia  0/103 (0.00%)  2/113 (1.77%) 
Thrombosis  0/103 (0.00%)  1/113 (0.88%) 
Varicose Vein  0/103 (0.00%)  1/113 (0.88%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Jenny Ibarra
Organization: Duke University
Phone: 919.236.3291
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00763867     History of Changes
Other Study ID Numbers: Pro00018007
U01HL084904 ( U.S. NIH Grant/Contract )
U01HL084904-01 ( U.S. NIH Grant/Contract )
521
First Submitted: September 30, 2008
First Posted: October 1, 2008
Results First Submitted: April 4, 2013
Results First Posted: July 3, 2013
Last Update Posted: July 23, 2014