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 pulmonary vascular resistance following treatment.

Condition	Intervention	Phase
Hernia, Diaphragmatic Hypertension, Pulmonary Hypoplasia, Lung	Drug: sildenafil	Phase IV

Further Study Details: 

Primary Outcomes: Pulmonary vascular resistance at final cardiac catheterization (7 weeks from initial cardiac catheterization)
Secondary Outcomes: Pulmonary arterial pressure at final cardiac catheterization (7 weeks); Pulmonary metabolism of vasoactive substances at final cardiac catheterization (7 weeks); Adverse effects of sildenafil therapy; Somatic growth at 1 and 2 years of age; Neurodevelopmental outcome at 1 and 2 years of age; Respiratory status at 1 and 2 years of age
Expected Total Enrollment:  32

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 cardiac catheterization to assess the degree of pulmonary hypertension and the pulmonary vascular resistance. They will then begin either sildenafil or placebo therapy for a 45d course. A final cardiac catheterization will be performed after the experimental drug course is completed. The pulmonary vascular resistance and pulmonary arterial pressure during hyperoxic conditions will be compared between the sildenafil and placebo groups. Infants from either group who have severely elevated pulmonary arterial pressure or pulmonary vascular resistance at the final cardiac catheterization (despite supplemental O2) will be started on sildenafil, which will continue after hospital discharge.

Ages Eligible for Study:  up to  42 Days,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Congenital diaphragmatic hernia
• 10-42 days 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 >=48h 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/ASD)

• 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00133679

Roberta L Keller, MD      415-514-3192    kellerr@peds.ucsf.edu
Samuel Hawgood, MBBS      415-476-9181    hawgoods@peds.ucsf.edu

California
      Children''''s Hospital of Los Angeles, Los Angeles,  California,  90027,  United States; Not yet recruiting
      University of California San Francisco Children''''s Hospital, San Francisco,  California,  94143,  United States; Recruiting

Study chairs or principal investigators

Roberta L Keller, MD,  Principal Investigator,  University of California, San Francisco   

Study ID Numbers:  K12HD49077-01
Last Updated:  August 22, 2005
Record first received:  August 22, 2005
ClinicalTrials.gov Identifier:  NCT00133679
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-08-23