Trial Outcomes & Findings for Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study) (NCT NCT00763867)
NCT ID: NCT00763867
Last Updated: 2014-07-23
Results Overview
COMPLETED
PHASE3
216 participants
Change from Baseline to Week 24
2014-07-23
Participant Flow
Participant milestones
| Measure |
Placebo
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
103
|
113
|
|
Overall Study
COMPLETED
|
98
|
101
|
|
Overall Study
NOT COMPLETED
|
5
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study)
Baseline characteristics by cohort
| Measure |
Placebo
n=103 Participants
20 mg tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=113 Participants
20 mg tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Total
n=216 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=93 Participants
|
38 Participants
n=4 Participants
|
80 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
61 Participants
n=93 Participants
|
75 Participants
n=4 Participants
|
136 Participants
n=27 Participants
|
|
Age, Continuous
|
68.7 years
STANDARD_DEVIATION 10.1 • n=93 Participants
|
68.4 years
STANDARD_DEVIATION 10.5 • n=4 Participants
|
68.5 years
STANDARD_DEVIATION 10.3 • n=27 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=93 Participants
|
49 Participants
n=4 Participants
|
104 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=93 Participants
|
64 Participants
n=4 Participants
|
112 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
93 participants
n=93 Participants
|
101 participants
n=4 Participants
|
194 participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
10 participants
n=93 Participants
|
12 participants
n=4 Participants
|
22 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=94 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=91 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Exercise Capacity, as Determined by Peak Oxygen Uptake
|
-0.07 ml/min/kg
Standard Deviation 2.00
|
-0.12 ml/min/kg
Standard Deviation 2.29
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 12Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=96 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=97 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Exercise Capacity, as Determined by Peak Oxygen Uptake
|
0.02 ml/min/kg
Standard Deviation 1.70
|
0.03 ml/min/kg
Standard Deviation 2.20
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 12Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
6 Minute Walk Distance
Outcome measures
| Measure |
Placebo
n=96 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=99 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Exercise Capacity as Determined by Walk Distance
|
26.2 meters
Standard Deviation 83.7
|
5.2 meters
Standard Deviation 69.1
|
SECONDARY outcome
Timeframe: Measured at Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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)
Outcome measures
| Measure |
Placebo
n=94 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Composite Score Reflective of Clinical Status
|
95.8 units on a scale
Standard Deviation 55.0
|
94.2 units on a scale
Standard Deviation 54.6
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
6 minute walk distance
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=90 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Exercise Capacity as Determined by Walk Distance
|
17.5 meters
Standard Deviation 88.6
|
12.0 meters
Standard Deviation 94.2
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 12Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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
Outcome measures
| Measure |
Placebo
n=91 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=88 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Cardiopulmonary Exercise Test (CPET) Duration
|
0.25 minutes
Standard Deviation 1.61
|
-0.15 minutes
Standard Deviation 1.60
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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
Outcome measures
| Measure |
Placebo
n=89 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=86 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Cardiopulmonary Exercise Test (CPET) Duration
|
9.82 minutes
Standard Deviation 2.63
|
9.77 minutes
Standard Deviation 3.21
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 12Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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
Outcome measures
| Measure |
Placebo
n=96 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=92 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Ventilatory Anaerobic Threshold
|
-0.01 ml/min/kg
Standard Deviation 1.14
|
0.06 ml/min/kg
Standard Deviation 1.24
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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
Outcome measures
| Measure |
Placebo
n=94 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=88 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Ventilatory Anaerobic Threshold
|
-0.10 ml/min/kg
Standard Deviation 1.26
|
0.17 ml/min/kg
Standard Deviation 1.26
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 12Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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
Outcome measures
| Measure |
Placebo
n=97 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Minnesota Living With Heart Failure Questionnaire (MLWHFQ)
|
-8.3 units on a scale
Standard Deviation 22.0
|
-6.2 units on a scale
Standard Deviation 20.8
|
SECONDARY outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
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.
Outcome measures
| Measure |
Placebo
n=91 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=91 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Minnesota Living With Heart Failure Questionnaire
|
-9.2 units on a scale
Standard Deviation 24.2
|
-8.3 units on a scale
Standard Deviation 19.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in LV Mass is considered an improvement
Outcome measures
| Measure |
Placebo
n=47 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=49 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Left Ventricular Mass
|
0.29 gm
Standard Deviation 14.43
|
-0.07 gm
Standard Deviation 14.93
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Left Ventricular Mass Index is considered an improvement
Outcome measures
| Measure |
Placebo
n=47 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=49 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Left Ventricular Mass Index
|
0.47 gm/m^2
Standard Deviation 6.54
|
0.61 gm/m^2
Standard Deviation 6.96
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in Left Ventricular End Diastolic Volume is considered an improvement
Outcome measures
| Measure |
Placebo
n=103 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=113 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Left Ventricular End Diastolic Volume
|
-3.70 mL
Standard Deviation 21.03
|
3.61 mL
Standard Deviation 25.02
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in Left Ventricular End Diastolic Volume Index is considered an improvement
Outcome measures
| Measure |
Placebo
n=47 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=49 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Left Ventricular End Diastolic Volume Index
|
-1.73 mL/m^2
Standard Deviation 9.45
|
2.11 mL/m^2
Standard Deviation 11.21
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in Left Ventricular End Systolic Volume Index is considered an improvement
Outcome measures
| Measure |
Placebo
n=47 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=49 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Left Ventricular End Systolic Volume Index
|
-0.82 mL/m^2
Standard Deviation 4.09
|
0.25 mL/m^2
Standard Deviation 6.12
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in LVEF is considered an improvement
Outcome measures
| Measure |
Placebo
n=47 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=49 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Left Ventricular Ejection Fraction (LVEF)
|
0.55 percentage of volume
Standard Deviation 4.28
|
0.62 percentage of volume
Standard Deviation 4.88
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Left Ventricular Mass is considered an improvement
Outcome measures
| Measure |
Placebo
n=56 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=58 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Echocardiogram Left Ventricular Mass
|
-1.93 gm
Standard Deviation 47.36
|
-8.79 gm
Standard Deviation 35.60
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Medial Diastolic Elastance is considered an improvement
Outcome measures
| Measure |
Placebo
n=72 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=68 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Medial Diastolic Elastance
|
-0.03 (m/sec)/cc
Standard Deviation 0.11
|
-0.01 (m/sec)/cc
Standard Deviation 0.10
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Lateral Diastolic Elastance is considered an improvement
Outcome measures
| Measure |
Placebo
n=67 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=67 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Lateral Diastolic Elastance
|
-0.00 (m/sec)/cc
Standard Deviation 0.09
|
-0.01 (m/sec)/cc
Standard Deviation 0.08
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in Left Ventricular relaxation is considered to be an improvement
Outcome measures
| Measure |
Placebo
n=83 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=77 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Medial Left Ventricular Relaxation
|
0.00 m/sec
Standard Deviation 0.02
|
-0.00 m/sec
Standard Deviation 0.02
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in Left Ventricular relaxation is considered to be an improvement
Outcome measures
| Measure |
Placebo
n=78 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=74 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Lateral Left Ventricular Relaxation
|
-0.00 m/sec
Standard Deviation 0.02
|
-0.00 m/sec
Standard Deviation 0.02
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in medial filling pressure is considered an improvement
Outcome measures
| Measure |
Placebo
n=80 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=75 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Medial Filling Pressure
|
-1.64 m/sec
Standard Deviation 6.83
|
0.33 m/sec
Standard Deviation 6.04
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in lateral filling pressure is considered an improvement
Outcome measures
| Measure |
Placebo
n=75 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=72 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Lateral Filling Pressure
|
-0.44 m/sec
Standard Deviation 5.17
|
-0.04 m/sec
Standard Deviation 5.68
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Effective Arterial Elastance is considered an improvement
Outcome measures
| Measure |
Placebo
n=76 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=68 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
ECHO Effective Arterial Elastance
|
0.03 Farads-1
Standard Deviation 0.46
|
-0.07 Farads-1
Standard Deviation 0.36
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Systemic Vascular Resistance is considered an improvement
Outcome measures
| Measure |
Placebo
n=74 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=66 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
ECHO Systemic Vascular Resistance
|
0.01 Woods units
Standard Deviation 0.46
|
-0.01 Woods units
Standard Deviation 0.35
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Effective Arterial Elastance is considered an improvement
Outcome measures
| Measure |
Placebo
n=45 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=47 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Effective Arterial Elastance
|
0.04 Farads-1
Standard Deviation 0.44
|
-0.15 Farads-1
Standard Deviation 0.38
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Systemic Vascular Resistance is considered an improvement
Outcome measures
| Measure |
Placebo
n=45 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=47 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Systemic Vascular Resistance
|
0.06 Woods units
Standard Deviation 0.57
|
-0.10 Woods units
Standard Deviation 0.39
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Aortic Thickness is considered an improvement
Outcome measures
| Measure |
Placebo
n=33 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=31 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Aortic Thickness
|
0.01 mm
Standard Deviation 0.17
|
-0.03 mm
Standard Deviation 0.18
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
An increase in Aortic Distensibility is considered to be an improvement
Outcome measures
| Measure |
Placebo
n=31 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=29 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
MRI Aortic Distensibility
|
0.12 cm^2*dyne-1
Standard Deviation 0.66
|
0.29 cm^2*dyne-1
Standard Deviation 1.13
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
A decrease in Pulmonary Artery Systolic Pressure is considered to be an improvement
Outcome measures
| Measure |
Placebo
n=58 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=45 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
ECHO Pulmonary Artery Systolic Pressure
|
-0.15 mmHg
Standard Deviation 12.43
|
0.32 mmHg
Standard Deviation 10.09
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Best available=local lab results only when core lab results not available
Outcome measures
| Measure |
Placebo
n=98 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=100 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Best Available Creatinine
|
0.02 mg/dL
Standard Deviation 0.23
|
0.09 mg/dL
Standard Deviation 0.29
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Best available=local lab results when core lab results not available
Outcome measures
| Measure |
Placebo
n=98 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=100 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Best Available Glomerular Filtration Rate (GFR)
|
-0.91 mL/min/1.73m^2
Standard Deviation 15.02
|
-3.27 mL/min/1.73m^2
Standard Deviation 12.16
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Cystatin C
|
-0.01 mg/L
Standard Deviation 0.27
|
0.10 mg/L
Standard Deviation 0.29
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=94 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=94 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Uric Acid
|
-0.11 mg/dL
Standard Deviation 1.79
|
0.51 mg/dL
Standard Deviation 1.80
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=94 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)
|
-50.52 pg/mL
Standard Deviation 799.87
|
158.25 pg/mL
Standard Deviation 538.85
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Aldosterone
|
7.04 pg/mL
Standard Deviation 220.06
|
1.22 pg/mL
Standard Deviation 213.47
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=93 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
High Sensitivity Troponin I
|
3.88 pg/mL
Standard Deviation 29.71
|
11.11 pg/mL
Standard Deviation 62.49
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=93 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Procollagen III N-terminal Peptide
|
0.58 ug/L
Standard Deviation 5.22
|
0.41 ug/L
Standard Deviation 3.90
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Endothelin-1
|
0.04 pg/mL
Standard Deviation 1.51
|
0.49 pg/mL
Standard Deviation 1.29
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
High Sensitivity C-Reactive Protein
|
0.36 mg/L
Standard Deviation 7.20
|
0.32 mg/L
Standard Deviation 5.49
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Collagen Type I (CITP)
|
-0.17 ug/L
Standard Deviation 4.03
|
5.61 ug/L
Standard Deviation 48.96
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=95 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=95 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Cyclic Guanosine Monophosphate (cGMP)
|
1.28 pmol/mL
Standard Deviation 37.05
|
8.72 pmol/mL
Standard Deviation 30.22
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=93 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=92 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Galectin 3
|
1.10 ng/mL
Standard Deviation 9.63
|
1.26 ng/mL
Standard Deviation 7.71
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Change from Baseline to Week 24Population: Participants analyzed consisted of those participants who had the endpoint data available to be derived.
Outcome measures
| Measure |
Placebo
n=98 Participants
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=100 Participants
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Furosemide-Equivalent Dose
|
-0.23 mg
Standard Deviation 35.44
|
7.27 mg
Standard Deviation 59.53
|
Adverse Events
Placebo
Sildenafil
Serious adverse events
| Measure |
Placebo
n=103 participants at risk
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=113 participants at risk
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.97%
1/103
|
0.88%
1/113
|
|
Cardiac disorders
Angina Pectoris
|
0.97%
1/103
|
0.00%
0/113
|
|
Cardiac disorders
Angina Unstable
|
0.97%
1/103
|
0.88%
1/113
|
|
Cardiac disorders
Atrial Fibrillation
|
1.9%
2/103
|
0.88%
1/113
|
|
Cardiac disorders
Atrioventricular Block Second Degree
|
0.00%
0/103
|
0.88%
1/113
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/103
|
0.88%
1/113
|
|
Cardiac disorders
Cardiac Failure
|
6.8%
7/103
|
8.0%
9/113
|
|
Cardiac disorders
Cardiac Failure Acute
|
2.9%
3/103
|
1.8%
2/113
|
|
Cardiac disorders
Palpitations
|
0.00%
0/103
|
0.88%
1/113
|
|
Cardiac disorders
Sinus Bradycardia
|
0.00%
0/103
|
0.88%
1/113
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/103
|
0.88%
1/113
|
|
Cardiac disorders
Ventricular Tachycardia
|
0.00%
0/103
|
0.88%
1/113
|
|
Vascular disorders
Hypertension
|
1.9%
2/103
|
0.00%
0/113
|
|
Vascular disorders
Hypertensive Emergency
|
0.97%
1/103
|
0.00%
0/113
|
|
Vascular disorders
Hypotension
|
0.00%
0/103
|
0.88%
1/113
|
|
Infections and infestations
Implant Site Infection
|
0.00%
0/103
|
0.88%
1/113
|
|
Infections and infestations
Pneumonia
|
0.97%
1/103
|
3.5%
4/113
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/103
|
0.88%
1/113
|
Other adverse events
| Measure |
Placebo
n=103 participants at risk
placebo 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
Sildenafil
n=113 participants at risk
sildenafil 20 mg three tid for 12 weeks followed by 60 mg tid for 12 weeks
|
|---|---|---|
|
Cardiac disorders
Angina Pectoris
|
1.9%
2/103
|
0.00%
0/113
|
|
Cardiac disorders
Atrial Fibrillation
|
3.9%
4/103
|
0.00%
0/113
|
|
Cardiac disorders
Atrial Flutter
|
0.97%
1/103
|
0.88%
1/113
|
|
Cardiac disorders
Atrioventricular Block Second Degree
|
0.97%
1/103
|
0.00%
0/113
|
|
Cardiac disorders
Cardiac Failure
|
0.97%
1/103
|
4.4%
5/113
|
|
Cardiac disorders
Palpitations
|
3.9%
4/103
|
4.4%
5/113
|
|
Cardiac disorders
Sinus Tachycardia
|
0.00%
0/103
|
0.88%
1/113
|
|
Vascular disorders
Flushing
|
2.9%
3/103
|
8.0%
9/113
|
|
Vascular disorders
Hot Flush
|
0.00%
0/103
|
1.8%
2/113
|
|
Vascular disorders
Hypertension
|
0.97%
1/103
|
0.00%
0/113
|
|
Vascular disorders
Hypotension
|
0.97%
1/103
|
7.1%
8/113
|
|
Vascular disorders
Perhipheral Coldness
|
0.00%
0/103
|
0.88%
1/113
|
|
Vascular disorders
Peripheral Ischaemia
|
0.00%
0/103
|
1.8%
2/113
|
|
Vascular disorders
Thrombosis
|
0.00%
0/103
|
0.88%
1/113
|
|
Vascular disorders
Varicose Vein
|
0.00%
0/103
|
0.88%
1/113
|
|
Nervous system disorders
Balance Disorder
|
0.00%
0/103
|
0.88%
1/113
|
|
Nervous system disorders
Dizziness
|
10.7%
11/103
|
8.0%
9/113
|
|
Nervous system disorders
Dizziness Postural
|
0.97%
1/103
|
0.00%
0/113
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/103
|
0.88%
1/113
|
|
Nervous system disorders
Headache
|
15.5%
16/103
|
23.9%
27/113
|
|
Nervous system disorders
Memory Impairment
|
0.00%
0/103
|
0.88%
1/113
|
|
Nervous system disorders
Parosmia
|
0.00%
0/103
|
0.88%
1/113
|
|
Nervous system disorders
Presyncope
|
0.00%
0/103
|
1.8%
2/113
|
|
Nervous system disorders
Syncope
|
1.9%
2/103
|
0.00%
0/113
|
|
Nervous system disorders
Tremor
|
0.00%
0/103
|
0.88%
1/113
|
|
Gastrointestinal disorders
Diarhea
|
13.6%
14/103
|
12.4%
14/113
|
|
Ear and labyrinth disorders
Tinnitis
|
3.9%
4/103
|
2.7%
3/113
|
|
Eye disorders
Visual Impairment
|
4.9%
5/103
|
6.2%
7/113
|
|
General disorders
Non-Cardiac Chest Pain
|
3.9%
4/103
|
0.00%
0/113
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place