Sildenafil After the Fontan Operation

NCT00507819 | Completed Phase 2 Results

• 1 other identifier: IRB 2007-4-5034
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this study, the investigators will evaluate the effect of sildenafil on exercise tolerance in patients with a single cardiac ventricle who have undergone the Fontan operation. The investigators will also evaluate echocardiographic measures of ventricular function and measure quality of life changes using two validated quality of life measures. The hypothesis is that sildenafil will result in increased exercise tolerance in patients who have had the Fontan operation as compared to placebo.

Conditions

Hypoplastic Left Heart Syndrome; Tricuspid Atresia

Keywords

Other Single Ventricle Anatomy; Hypoplastic Left Heart Syndrome; Tricuspid Atresia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean Oxygen Consumption (mL/kg/Min) at 6 Weeks

  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.

  Baseline and 6 Weeks

Secondary Outcomes (3)

• Change From Baseline in Mean Heart Rate (Bpm) at 6 Weeks

  Baseline and 6 Weeks

• Change From Baseline in Mean Respiratory Rate (Breaths/Min) at 6 Weeks

  Baseline and 6 Weeks

• Change From Baseline in Mean Minute Ventilation (L/Min) at 6 Weeks

  Baseline and 6 Weeks

Study Arms (2)

Sildenafil, then Placebo

ACTIVE COMPARATOR

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.

Drug: Sildenafil; Drug: Placebo

Placebo, then Sildenafil

ACTIVE COMPARATOR

Placebo will be given for 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

Drug: Sildenafil; Drug: Placebo

Interventions

Sildenafil DRUG

One 20 mg capsule of sildenafil will be taken by mouth three times-a-day.

Also known as: Revatio, Viagra

Placebo, then Sildenafil; Sildenafil, then Placebo

Placebo DRUG

One placebo capsule will be taken by mouth three times-a-day.

Placebo, then Sildenafil; Sildenafil, then Placebo

Eligibility Criteria

• Age: 8 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years of age or older
• All participants must have had Fontan completion

You may not qualify if:

• Height less than 132 cm
• Unable to participate in exercise testing due to medical restrictions or physical limitations
• Fontan baffle obstruction or single lung physiology
• Coarctation of the aorta or neo-aorta (BP gradient \> 20 mmHg)
• Severe ventricular dysfunction assessed qualitatively by echocardiography
• Severe atrioventricular valvar regurgitation assessed qualitatively by echocardiography
• Presence of electronic pacemaker
• History of treatment with sildenafil in the six weeks prior to enrollment in study
• Patients with severe renal impairment
• Patients with severe hepatic impairment
• Patients taking medications that inhibit or induce Cytochrome P450 3A4 (CYP3A4) (including grapefruit juice and St. John's Wort)
• Patients taking alpha-blockers and nitrates
• Parents/guardians or subjects who, in the opinion of the investigator, may be non-compliant with study schedules or procedures

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• The Mark H. and Blanche M. Harrington Foundation: collaborator

Related Publications (1)

• Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation. 2011 Mar 22;123(11):1185-93. doi: 10.1161/CIRCULATIONAHA.110.981746. Epub 2011 Mar 7.

  PMID: 21382896 DERIVED

MeSH Terms

Conditions

Hypoplastic Left Heart Syndrome; Tricuspid Atresia

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

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.

Results Point of Contact

• Title: David J. Goldberg, MD
• Organization: The Children's Hospital of Philadelphia

goldbergda@email.chop.edu

267-426-8143

Study Officials

• Jack Rychik, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 27, 2007
• Study Start: December 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 5, 2015
• Results First Posted: May 5, 2015

Record last verified: 2015-05