Chronic Sildenafil for Severe Diaphragmatic Hernia

This study has been 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)
Sponsor:
Collaborators:
Children's Hospital Los Angeles
Ann & Robert H Lurie Children's Hospital of Chicago
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00133679
First received: August 22, 2005
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Hernia, Diaphragmatic
Hypertension, Pulmonary
Hypoplasia, Pulmonary
Drug: sildenafil
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Chronic Sildenafil for Severe Diaphragmatic Hernia

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Estimated systolic pulmonary arterial pressure at final echocardiogram [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Systemic levels of vasoactive substances at the time of final echocardiogram [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
  • Adverse effects of sildenafil therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Somatic growth at 1 and 2 years of age [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Neurodevelopmental outcome at 1 and 2 years of age [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Respiratory status at 1 and 2 years of age [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: February 2006
Study Completion Date: October 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   up to 42 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00133679

Locations
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
Investigators
Principal Investigator: Roberta L Keller, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00133679     History of Changes
Other Study ID Numbers: K23HL79922-01
Study First Received: August 22, 2005
Last Updated: August 11, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Hypertension
Hernia
Hypertension, Pulmonary
Hernia, Diaphragmatic
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Lung Diseases
Respiratory Tract Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 18, 2014