Chronic Sildenafil for Severe Diaphragmatic Hernia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00133679
Recruitment Status : Terminated (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)
First Posted : August 23, 2005
Last Update Posted : August 13, 2014
Children's Hospital Los Angeles
Ann & Robert H Lurie Children's Hospital of Chicago
Information provided by (Responsible Party):
University of California, San Francisco

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.

Condition or disease Intervention/treatment Phase
Hernia, Diaphragmatic Hypertension, Pulmonary Hypoplasia, Pulmonary Drug: sildenafil Drug: Placebo Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Chronic Sildenafil for Severe Diaphragmatic Hernia
Study Start Date : February 2006
Actual Primary Completion Date : July 2013
Actual Study Completion Date : October 2013

Arm Intervention/treatment
Experimental: 1
Sildenafil x 45 days
Drug: sildenafil
Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
Other Name: Viagra, Revatio

Placebo Comparator: 2
Placebo x 45 d
Drug: Placebo
Placebo suspension (equal volume to experimental drug) x 45 days

Primary Outcome Measures :
  1. Estimated systolic pulmonary arterial pressure at final echocardiogram [ Time Frame: 7 weeks ]

Secondary Outcome Measures :
  1. Systemic levels of vasoactive substances at the time of final echocardiogram [ Time Frame: 7 weeks ]
  2. Adverse effects of sildenafil therapy [ Time Frame: 2 years ]
  3. Somatic growth at 1 and 2 years of age [ Time Frame: 2 years ]
  4. Neurodevelopmental outcome at 1 and 2 years of age [ Time Frame: 2 years ]
  5. Respiratory status at 1 and 2 years of age [ Time Frame: 2 years ]

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Ages Eligible for Study:   up to 42 Days   (Child)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00133679

United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
University of California San Francisco Children's Hospital
San Francisco, California, United States, 94143
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
Sponsors and Collaborators
University of California, San Francisco
Children's Hospital Los Angeles
Ann & Robert H Lurie Children's Hospital of Chicago
Principal Investigator: Roberta L Keller, MD University of California, San Francisco

Responsible Party: University of California, San Francisco Identifier: NCT00133679     History of Changes
Other Study ID Numbers: K23HL079922-01 ( U.S. NIH Grant/Contract )
First Posted: August 23, 2005    Key Record Dates
Last Update Posted: August 13, 2014
Last Verified: August 2014

Keywords provided by University of California, San Francisco:
Chronic lung disease
Nitric oxide
cyclic guanosine monophosphate
phosphodiesterase inhibitor

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hernia, Diaphragmatic
Hernias, Diaphragmatic, Congenital
Pathological Conditions, Anatomical
Lung Diseases
Respiratory Tract Diseases
Congenital Abnormalities
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents