Chronic Sildenafil for Severe Diaphragmatic Hernia

NCT ID: NCT00133679

Last Updated: 2021-01-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2013-10-31

Brief 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.

Detailed 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.

Conditions

Hernia, Diaphragmatic; Hypertension, Pulmonary; Hypoplasia, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Sildenafil x 45 days

Group Type: EXPERIMENTAL

sildenafil

Intervention Type: DRUG

Sildenafil 0.5 mg/kg every 6 hours orally x 45 d

2

Placebo x 45 d

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo suspension (equal volume to experimental drug) x 45 days

Interventions

sildenafil

Sildenafil 0.5 mg/kg every 6 hours orally x 45 d

Intervention Type: DRUG

Placebo

Placebo suspension (equal volume to experimental drug) x 45 days

Intervention Type: DRUG

Other Intervention Names

Viagra, Revatio

Eligibility Criteria

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

• Minimum Eligible Age: 10 Days
• Maximum Eligible Age: 42 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Los Angeles

OTHER

Sponsor Role: collaborator

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberta L Keller, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Children's Hospital of Los Angeles

Los Angeles, California, United States

University of California San Francisco Children's Hospital

San Francisco, California, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Countries

United States

Other Identifiers

K23HL079922-01

Identifier Type: NIH

Identifier Source: org_study_id

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