Clinical trial NCT00133679: Chronic Sildenafil for Severe Diaphragmatic Hernia
Official title: Chronic Sildenafil for Severe Diaphragmatic Hernia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hernia, Diaphragmatic
Hypertension, Pulmonary
Hypoplasia, Pulmonary
Keywords: Chronic lung disease
Nitric oxide
cyclic guanosine monophosphate
phosphodiesterase inhibitor
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Children's Hospital Los Angeles
name: Ann & Robert H Lurie Children's Hospital of Chicago
First posted: 2005-08-23
Enrollment: 9
Sex: ALL
Minimum age (years): 10
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram
timeFrame: 7 weeks
Secondary outcomes:
measure: Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram
timeFrame: 7 weeks
measure: Adverse Effects of Sildenafil Therapy
timeFrame: 2 years
measure: Somatic Growth at 1 and 2 Years of Age
timeFrame: 2 years
measure: Neurodevelopmental Outcome at 1 and 2 Years of Age
timeFrame: 2 years
measure: Respiratory Status at 1 and 2 Years of Age
timeFrame: 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Children's Hospital
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
Study officials:
affiliation: University of California, San Francisco
name: Roberta L Keller, MD
role: PRINCIPAL_INVESTIGATOR
References: