Chronic Sildenafil for Severe Diaphragmatic Hernia

University of California San Francisco (UCSF)

Status and phase

Terminated

Phase 4

Conditions

Hypertension, Pulmonary

Hypoplasia, Pulmonary

Hernia, Diaphragmatic

Treatments

Drug: Placebo

Drug: sildenafil

Study type

Interventional

Funder types

Other

Identifiers

NCT00133679

K23HL079922-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

9 patients

Sex

All

Ages

10 to 42 days old

Volunteers

No Healthy Volunteers

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