Trial Outcomes & Findings for Sildenafil After the Fontan Operation (NCT NCT00507819)

Last Updated: 2015-05-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Baseline and 6 Weeks

Results posted on

2015-05-05

Participant Flow

Of 125 eligible subjects contacted by the study team, 28 (22%) participated in the study.

Participant milestones

Participant milestones
Measure	Sildenafil, Then Placebo 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, Then Sildenafil 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
First Intervention (6 Weeks) STARTED	14	14
First Intervention (6 Weeks) COMPLETED	14	14
First Intervention (6 Weeks) NOT COMPLETED	0	0
Washout (6 Weeks) STARTED	14	14
Washout (6 Weeks) COMPLETED	13	14
Washout (6 Weeks) NOT COMPLETED	1	0
Second Intervention (6 Weeks) STARTED	13	14
Second Intervention (6 Weeks) COMPLETED	13	14
Second Intervention (6 Weeks) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sildenafil, Then Placebo 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, Then Sildenafil 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
Washout (6 Weeks) Withdrawal by Subject	1	0

Baseline Characteristics

Sildenafil After the Fontan Operation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Population n=28 Participants Subjects who were randomized to receive either Sildenafil 20mg three times a day by mouth or Placebo three times a day by mouth.
Age, Continuous	14.9 Years STANDARD_DEVIATION 5.1 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 Weeks

Outcome measures

Outcome measures
Measure	Sildenafil n=28 Participants Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks	Placebo n=27 Participants Placebo was given by mouth three times a day for six weeks
Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks Oxygen Consumption at Baseline (mL/kg/min)	30.5 mL/kg/min Standard Deviation 6.9	30.5 mL/kg/min Standard Deviation 6.9
Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks Oxygen Consumption at 6 Weeks (mL/kg/min)	31.3 mL/kg/min Standard Deviation 7.1	31.3 mL/kg/min Standard Deviation 7.5

SECONDARY outcome

Timeframe: Baseline and 6 Weeks

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.

Outcome measures

Outcome measures
Measure	Sildenafil n=28 Participants Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks	Placebo n=27 Participants Placebo was given by mouth three times a day for six weeks
Change From Baseline in Mean Heart Rate (Bpm) at 6 Weeks Heart rate at Baseline (bpm)	163 bpm Standard Deviation 20	163 bpm Standard Deviation 15
Change From Baseline in Mean Heart Rate (Bpm) at 6 Weeks Heart rate at 6 Weeks (bpm)	163 bpm Standard Deviation 14	163 bpm Standard Deviation 15

SECONDARY outcome

Timeframe: Baseline and 6 Weeks

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.

Outcome measures

Outcome measures
Measure	Sildenafil n=28 Participants Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks	Placebo n=27 Participants Placebo was given by mouth three times a day for six weeks
Change From Baseline in Mean Respiratory Rate (Breaths/Min) at 6 Weeks Mean Respiratory rate at Baseline (breaths/min)	53.7 breaths/min Standard Deviation 8.9	53.0 breaths/min Standard Deviation 7.5
Change From Baseline in Mean Respiratory Rate (Breaths/Min) at 6 Weeks Mean Respiratory rate at 6 Weeks (breaths/min)	51.0 breaths/min Standard Deviation 9.4	53.0 breaths/min Standard Deviation 8.3

SECONDARY outcome

Timeframe: Baseline and 6 Weeks

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.

Outcome measures

Outcome measures
Measure	Sildenafil n=28 Participants Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks	Placebo n=27 Participants Placebo was given by mouth three times a day for six weeks
Change From Baseline in Mean Minute Ventilation (L/Min) at 6 Weeks Minute Ventilation at Baseline (L/min)	68.8 L/min Standard Deviation 25	68.1 L/min Standard Deviation 27
Change From Baseline in Mean Minute Ventilation (L/Min) at 6 Weeks Minute Ventilation at 6 Weeks (L/min)	67.2 L/min Standard Deviation 23	68.8 L/min Standard Deviation 26

Adverse Events

Sildenafil

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sildenafil n=28 participants at risk Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks	Placebo n=27 participants at risk Placebo was given by mouth three times a day for six weeks
Gastrointestinal disorders Constipation	3.6% 1/28 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	0.00% 0/27 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.

Other adverse events

Other adverse events
Measure	Sildenafil n=28 participants at risk Sildenafil was given by mouth at a dose of 20 mg three times a day for six weeks	Placebo n=27 participants at risk Placebo was given by mouth three times a day for six weeks
General disorders Headache	32.1% 9/28 • Number of events 9 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	18.5% 5/27 • Number of events 5 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Vascular disorders Flushing	17.9% 5/28 • Number of events 5 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	0.00% 0/27 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
General disorders Dizziness	7.1% 2/28 • Number of events 2 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	7.4% 2/27 • Number of events 2 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Gastrointestinal disorders Nausea / vomiting	7.1% 2/28 • Number of events 2 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	0.00% 0/27 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Renal and urinary disorders Kidney Stone	3.6% 1/28 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	0.00% 0/27 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Eye disorders Photosensitivity	3.6% 1/28 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	0.00% 0/27 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Skin and subcutaneous tissue disorders Rash	3.6% 1/28 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	0.00% 0/27 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Gastrointestinal disorders Diarrhea	0.00% 0/28 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	3.7% 1/27 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Cardiac disorders Hypotension	0.00% 0/28 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	3.7% 1/27 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Musculoskeletal and connective tissue disorders Muscle Pain	0.00% 0/28 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	3.7% 1/27 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
Ear and labyrinth disorders Tinnitus	0.00% 0/28 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	3.7% 1/27 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.
General disorders Tremulous	0.00% 0/28 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.	3.7% 1/27 • Number of events 1 • 6 weeks for each intervention. Adverse event summary information includes all subjects who received at least one dose of study medication/placebo.

Additional Information

David J. Goldberg, MD

The Children's Hospital of Philadelphia

Phone: 267-426-8143

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place