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Change in clinical practice allowing chronic therapy at 6 weeks of age, incompatible with possibility of placebo beyond 6 weeks of age on study protocol
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| Name | Class |
|---|---|
| Children's Hospital Los Angeles | OTHER |
| Ann & Robert H Lurie Children's Hospital of Chicago | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Sildenafil x 45 days |
|
| 2 | Placebo Comparator | Placebo x 45 d |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sildenafil | Drug | Sildenafil 0.5 mg/kg every 6 hours orally x 45 d |
|
| Measure | Description | Time Frame |
|---|---|---|
| Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram | 7 weeks |
| Measure | Description | 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 |
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Inclusion Criteria:
Congenital diaphragmatic hernia
10-42 days (d) of age
Significant illness severity as demonstrated by:
Receiving assisted ventilation and
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):
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| Name | Affiliation | Role |
|---|---|---|
| Roberta L Keller, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Los Angeles | California | 90027 | United States | ||
| University of California San Francisco Children's Hospital |
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Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sildenafil | Sildenafil x 45 days sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d |
| FG001 | Placebo | Placebo x 45 d Placebo: Placebo suspension (equal volume to experimental drug) x 45 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sildenafil | Sildenafil x 45 days sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d |
| BG001 | Placebo | Placebo x 45 d Placebo: Placebo suspension (equal volume to experimental drug) x 45 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram | Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed. | Posted | 7 weeks |
|
|
Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sildenafil | Sildenafil x 45 days sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roberta Keller, MD | University of California, San Francisco | (415) 476-1888 | roberta.keller@ucsf.edu |
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| ID | Term |
|---|---|
| D006548 | Hernia, Diaphragmatic |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D000082122 | Internal Hernia |
| D006547 | Hernia |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| Placebo | Drug | Placebo suspension (equal volume to experimental drug) x 45 days |
|
| 2 years |
| Neurodevelopmental Outcome at 1 and 2 Years of Age | 2 years |
| Respiratory Status at 1 and 2 Years of Age | 2 years |
| San Francisco |
| California |
| 94143 |
| United States |
| Children's Memorial Hospital | Chicago | Illinois | 60614 | United States |
| BG002 | Total | Total of all reporting groups |
|
| Sex: Female, Male |
|
| Region of Enrollment | participants |
|
| Participants |
|
| Secondary | Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram | Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed. | Posted | 7 weeks |
|
|
| Secondary | Adverse Effects of Sildenafil Therapy | Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed. | Posted | 2 years |
|
|
| Secondary | Somatic Growth at 1 and 2 Years of Age | Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed. | Posted | 2 years |
|
|
| Secondary | Neurodevelopmental Outcome at 1 and 2 Years of Age | Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed. | Posted | 2 years |
|
|
| Secondary | Respiratory Status at 1 and 2 Years of Age | Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed. | Posted | 2 years |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Placebo | Placebo x 45 d Placebo: Placebo suspension (equal volume to experimental drug) x 45 days | 0 | 0 | 0 | 0 | 0 | 0 |
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| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |