Hernia, Diaphragmatic, Hypertension, Pulmonary, Hypoplasia, Pulmonary
Conditions
Keywords
Chronic lung disease, Nitric oxide, cyclic guanosine monophosphate, phosphodiesterase inhibitor
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.
Interventions
DRUGsildenafil
Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
DRUGPlacebo
Placebo suspension (equal volume to experimental drug) x 45 days
Sponsors
Children's Hospital Los Angeles
Ann & Robert H Lurie Children's Hospital of Chicago
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Days to 42 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram | 7 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram | 7 weeks |
| Adverse Effects of Sildenafil Therapy | 2 years |
| Somatic Growth at 1 and 2 Years of Age | 2 years |
| Neurodevelopmental Outcome at 1 and 2 Years of Age | 2 years |
| Respiratory Status at 1 and 2 Years of Age | 2 years |
Countries
United States
Participant flow
Recruitment details
Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Sildenafil x 45 days
sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d | 0 |
| Placebo Placebo x 45 d
Placebo: Placebo suspension (equal volume to experimental drug) x 45 days | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram
Time frame: 7 weeks
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Secondary
Adverse Effects of Sildenafil Therapy
Time frame: 2 years
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Secondary
Neurodevelopmental Outcome at 1 and 2 Years of Age
Time frame: 2 years
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Secondary
Respiratory Status at 1 and 2 Years of Age
Time frame: 2 years
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Secondary
Somatic Growth at 1 and 2 Years of Age
Time frame: 2 years
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Secondary
Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram
Time frame: 7 weeks
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.