The most common etiology of infection-related death or neurodevelopmental impairment in
neonates with birthweight <750 g is invasive candidiasis. Over 70% of the premature neonates
who develop invasive candidiasis will die or suffer severe, permanent neurologic impairment.
Fluconazole has been commonly used off-label in the neonatal intensive care unit, but
definitive recommendations for its use in the nursery have been hampered by the limited
number of well-designed trials. In neonates weighing <750 g, appropriate dosing is not
known, definitive safety and long-term follow up trials have not been completed, and there
have not been well-powered trials conducted to establish the efficacy of the product using
mortality as part of the primary endpoint. Three recent proof-of-concept studies suggest
that fluconazole will be safe and effective, and a recently completed pharmacokinetic study
is providing data to give preliminary dosing guidance. The next logical step in drug
development is proposed by this research: to conduct a pivotal trial to determine the safety
and efficacy of fluconazole in premature neonates with 2-year neurodevelopmental follow-up
assessment.
362 neonates, with a birthweight <750g, were randomized at 33 US centers, to twice weekly
fluconazole (6 mg/kg) or placebo for the first 6 weeks of life. The primary efficacy
endpoint will be Candida-free survival at study day 49. The research will establish
definitive dosing, safety, and efficacy of fluconazole; it will also provide critical
information on the effects of fluconazole on neurodevelopmental impairment and antifungal
resistance.
Potential Impact:
Approximately 17,000 neonates are born <750 grams each year in the United States. Over 5000
will die or develop invasive Candida infections. Demonstrating safety and efficacy of
fluconazole in preterm neonates will improve the survivability and long term outcomes for
these neonates.
Minimum age: N/A.
Maximum age: 5 Days.
Gender(s): Both.
University of Alabama at Birmingham, Birmingham, Alabama 35233, United States
Arkansas Childrens Hospital, Little Rock, Arkansas 72205, United States
University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202, United States
Children's Hospital of Orange County, Orange, California 92868, United States
University of California-San Diego, San Diego, California 92103, United States
University of Florida, Gainesville, Florida 32610, United States
Baptist Medical Center, Jacksonville, Florida 32209, United States
Shands Jacksonville Medical Center, Jacksonville, Florida 32209, United States
University of Miami, Miami, Florida 33136, United States
Riley Hospital, Indianapolis, Indiana 46601, United States
Memorial Hospital, South Bend, Indiana 46601, United States
Wesley Medical Center, Wichita, Kansas 67214, United States
Kosair Children's Hospital, Louisville, Kentucky 40202, United States
Tulane University School of Medicine, New Orleans, Louisiana 70112, United States
Wayne State University, Detroit, Michigan 48201, United States
University of Minnesota, Fairview Medical Center, Minneapolis, Minnesota 55455, United States
University of Nevada School of Medicine, Las Vegas, Nevada 89109, United States
West Jersey Hospital - Voorhees, Voorhees, New Jersey 08043, United States
Brookdale University Medical Center, Brooklyn, New York 11203, United States
Kings County Hospital Center, Brooklyn, New York 11203, United States
SUNY Dowstate Medical Center, Brooklyn, New York 11203, United States
Columbia University Medical Center, New York, New York 10032, United States
Duke University Medical Center, Durham, North Carolina 27705, United States
Pitt County Memorial Hospital, Greenville, North Carolina 27834, United States
Akron Children's Hospital, Akron, Ohio 44313, United States
Oregon Health Sciences Center, Portland, Oregon 97201, United States
Pennsylvania Hospital, Philadelphia, Pennsylvania 19107, United States
University of Tennessee, Memphis, Tennessee 38130, United States
Parkland Memorial Hospital, Dallas, Texas 75235, United States
Cooks Children's Medical Center, Fort Worth, Texas 76104, United States
University of Texas Medical Branch, Galveston, Texas 77555, United States
Texas Children's Hospital/Baylor College of Medicine, Houston, Texas 77030, United States
University of Texas - Houston, Houston, Texas 77030, United States