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Sildenafil After the Fontan Operation (SAFO)

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ClinicalTrials.gov Identifier: NCT00507819
Recruitment Status : Completed
First Posted : July 27, 2007
Results First Posted : May 5, 2015
Last Update Posted : May 5, 2015
Sponsor:
Collaborator:
The Mark H. and Blanche M. Harrington Foundation
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hypoplastic Left Heart Syndrome
Tricuspid Atresia
Interventions Drug: Sildenafil
Drug: Placebo
Enrollment 28
Recruitment Details Of 125 eligible subjects contacted by the study team, 28 (22%) participated in the study.
Pre-assignment Details  
Arm/Group Title Sildenafil, Then Placebo Placebo, Then Sildenafil
Hide Arm/Group Description Sildenafil will be given at a dose of 20 mg three times-a-day for six weeks followed by a six week washout period followed by placebo for an additional six weeks. Placebo six weeks followed by a six week washout period followed by Sildenafil which will be given at a dose of 20 mg three times-a-day for six weeks
Period Title: First Intervention (6 Weeks)
Started 14 14
Completed 14 14
Not Completed 0 0
Period Title: Washout (6 Weeks)
Started 14 14
Completed 13 14
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
Period Title: Second Intervention (6 Weeks)
Started 13 14
Completed 13 14
Not Completed 0 0
Arm/Group Title Study Population
Hide Arm/Group Description Subjects who were randomized to receive either Sildenafil 20mg three times a day by mouth or Placebo three times a day by mouth.
Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
All subjects who consented to participate and were randomized, completed at least the first six-week study period.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants
14.9  (5.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female
10
  35.7%
Male
18
  64.3%
1.Primary Outcome
Title Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks
Hide Description Oxygen consumption measurements were taken at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.
Time Frame Baseline and 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks
Placebo was given by mouth three times a day for six weeks
Overall Number of Participants Analyzed 28 27
Mean (Standard Deviation)
Unit of Measure: mL/kg/min
Oxygen Consumption at Baseline (mL/kg/min) 30.5  (6.9) 30.5  (6.9)
Oxygen Consumption at 6 Weeks (mL/kg/min) 31.3  (7.1) 31.3  (7.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Heart Rate (Bpm) at 6 Weeks
Hide Description Heart rate was measured at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.
Time Frame Baseline and 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks
Placebo was given by mouth three times a day for six weeks
Overall Number of Participants Analyzed 28 27
Mean (Standard Deviation)
Unit of Measure: bpm
Heart rate at Baseline (bpm) 163  (20) 163  (15)
Heart rate at 6 Weeks (bpm) 163  (14) 163  (15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Respiratory Rate (Breaths/Min) at 6 Weeks
Hide Description Respiratory rate was measured at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.
Time Frame Baseline and 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks
Placebo was given by mouth three times a day for six weeks
Overall Number of Participants Analyzed 28 27
Mean (Standard Deviation)
Unit of Measure: breaths/min
Mean Respiratory rate at Baseline (breaths/min) 53.7  (8.9) 53.0  (7.5)
Mean Respiratory rate at 6 Weeks (breaths/min) 51.0  (9.4) 53.0  (8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Mean Minute Ventilation (L/Min) at 6 Weeks
Hide Description Minute ventilation measurements were taken at peak exercise. Subjects were exercised to maximal volition with an electronically braked cycle ergometer. The protocol consisted of 3 minutes of pedaling in an unloaded state followed by a ramp increase in work rate (watts) to maximal exercise. Metabolic and ventilatory data were obtained throughout the exercise study and for the first 2 minutes of recovery on a breath-by-breath basis with a metabolic cart.
Time Frame Baseline and 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks
Placebo was given by mouth three times a day for six weeks
Overall Number of Participants Analyzed 28 27
Mean (Standard Deviation)
Unit of Measure: L/min
Minute Ventilation at Baseline (L/min) 68.8  (25) 68.1  (27)
Minute Ventilation at 6 Weeks (L/min) 67.2  (23) 68.8  (26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Time Frame 6 weeks for each intervention.
Adverse Event Reporting Description Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
 
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks Placebo was given by mouth three times a day for six weeks
All-Cause Mortality
Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Sildenafil Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/28 (3.57%)      0/27 (0.00%)    
Gastrointestinal disorders     
Constipation  [1]  1/28 (3.57%)  1 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Constipation-related abdominal pain
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sildenafil Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/28 (39.29%)      10/27 (37.04%)    
Cardiac disorders     
Hypotension   0/28 (0.00%)  0 1/27 (3.70%)  1
Ear and labyrinth disorders     
Tinnitus   0/28 (0.00%)  0 1/27 (3.70%)  1
Eye disorders     
Photosensitivity   1/28 (3.57%)  1 0/27 (0.00%)  0
Gastrointestinal disorders     
Nausea / vomiting  [1]  2/28 (7.14%)  2 0/27 (0.00%)  0
Diarrhea   0/28 (0.00%)  0 1/27 (3.70%)  1
General disorders     
Headache  [2]  9/28 (32.14%)  9 5/27 (18.52%)  5
Dizziness  [3]  2/28 (7.14%)  2 2/27 (7.41%)  2
Tremulous   0/28 (0.00%)  0 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders     
Muscle Pain   0/28 (0.00%)  0 1/27 (3.70%)  1
Renal and urinary disorders     
Kidney Stone   1/28 (3.57%)  1 0/27 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash   1/28 (3.57%)  1 0/27 (0.00%)  0
Vascular disorders     
Flushing  [4]  5/28 (17.86%)  5 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Nausea / vomiting
[2]
Headache
[3]
Dizziness
[4]
Non-painful facial flushing
Characteristics of screened but not enrolled subjects was not evaluated, so enrolled subjects may not be a representative sample from the group at large. Safety of Sildenafil over a prolonged (>6week) period of continuous use was not evaluated.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: David J. Goldberg, MD
Organization: The Children's Hospital of Philadelphia
Phone: 267-426-8143
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00507819     History of Changes
Other Study ID Numbers: IRB 2007-4-5034
First Submitted: July 25, 2007
First Posted: July 27, 2007
Results First Submitted: February 9, 2011
Results First Posted: May 5, 2015
Last Update Posted: May 5, 2015