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Sildenafil After the Fontan Operation (SAFO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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)
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)
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)
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)
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   --/--      --/--    
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
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
Layout table for Results Point of Contact information
Name/Title: David J. Goldberg, MD
Organization: The Children's Hospital of Philadelphia
Phone: 267-426-8143
EMail: goldbergda@email.chop.edu
Layout table for additonal information
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00507819    
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