Chronic Sildenafil for Severe Diaphragmatic Hernia

Hypertension, Pulmonary Clinical Trial

Official title:

Chronic Sildenafil for Severe Diaphragmatic Hernia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00133679
• Other study ID #: K23HL079922-01
• Status: Terminated
• Phase: Phase 4
• Start date: February 2006
• Est. completion date: October 2013

Study information

• Verified date: January 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test if sildenafil is effective in the treatment of infants with severe congenital diaphragmatic hernia (determined by the presence of prolonged pulmonary hypertension or prolonged oxygen supplementation on mechanical ventilation), as measured by the estimated pulmonary artery systolic pressure following treatment.

Description:

Congenital diaphragmatic hernia (CDH) is a condition characterized by pulmonary parenchymal and vascular hypoplasia. Severe CDH carries a high rate of mortality, and significant morbidity among survivors. This proposal is a randomized, blinded, placebo-controlled study designed to evaluate the efficacy and potential mechanisms of activity of sildenafil, a phosphodiesterase-5 inhibitor, for treatment of severe CDH. Infants who meet criteria at ≥10d of age predicting a poor outcome [death or chronic lung disease (CLD) severe enough to require hospital discharge on supplemental oxygen (O2)] will be eligible for the study. Infants whose parents consent for the study will undergo an initial echocardiogram to assess the degree of pulmonary hypertension. They will then begin either sildenafil or placebo therapy for a 45d course. A final echocardiogram will be performed after the experimental drug course is completed. The pulmonary arterial systolic pressure estimate during hyperoxic conditions will be compared between the sildenafil and placebo groups. Infants from either group who have severely elevated pulmonary arterial pressure (despite supplemental O2) will be considered for open-label sildenafil, which will continue after hospital discharge, depending on the results of a cardiac catheterization performed for clinical care.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: October 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 42 Days

Eligibility

Inclusion Criteria:

• Congenital diaphragmatic hernia

• 10-42 days (d) of age

• Significant illness severity as demonstrated by:

• Receiving assisted ventilation and

• FiO2 >= 0.40 at 10-14d of age, or

• FiO2 >= 0.40 for >=48hours at 15-27d of age, or

• FiO2 >= 0.35 at 28-42d of age

• Or, need for extracorporeal support at >=10d of age

• Or, estimated pulmonary arterial or right ventricular systolic pressure of >= 2/3 systemic pressure at 14-42d of age

Exclusion Criteria:

• Structural congenital heart disease (other than patent ductus arteriosus or patent foramen ovale/atrial septal defect [ASD] or non-hemodynamically significant ventricular septal defect [VSD])

• Sildenafil contraindicated (until condition resolves):

• Unable to absorb oral medication, or

• Unstable systemic blood pressure, or

• Receiving a drug that may interfere with sildenafil metabolism, or

• Renal insufficiency

• Hepatic insufficiency Previous use of sildenafil

Related Conditions & MeSH terms

• Hernia
• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital
• Hypertension, Pulmonary
• Hypoplasia, Pulmonary

Intervention

Drug:
• sildenafil
Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
• Placebo
Placebo suspension (equal volume to experimental drug) x 45 days

Locations

Country	Name	City	State
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	University of California San Francisco Children's Hospital	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Ann & Robert H Lurie Children's Hospital of Chicago, Children's Hospital Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram		7 weeks
Secondary	Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram		7 weeks
Secondary	Adverse Effects of Sildenafil Therapy		2 years
Secondary	Somatic Growth at 1 and 2 Years of Age		2 years
Secondary	Neurodevelopmental Outcome at 1 and 2 Years of Age		2 years
Secondary	Respiratory Status at 1 and 2 Years of Age		2 years