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Fluconazole Prophylaxis for the Prevention of Candidiasis in Infants Less Than 750 Grams Birthweight

Information source: Duke University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Candidiasis

Intervention: fluconazole (Drug); placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Daniel Benjamin

Official(s) and/or principal investigator(s):
Daniel K Benjamin, MD MPH PhD, Principal Investigator, Affiliation: Duke Univerisity Medical Center, Duke Clinical Research Institute

Summary

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.

Clinical Details

Official title: Fluconazole Prophylaxis for the Prevention of Candidiasis in Infants < 750 Grams Birth

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Death or Candidiasis

Secondary outcome:

Neurodevelopmental Impairment

Candidiasis

Stage II or Higher Necrotizing Enterocolitis

Focal Intestinal Perforation

Chronic Lung Disease

Patent Ductus Arterious Requiring Surgical Ligation

Periventricular Leukomalacia

Retinopathy of Prematurity Requiring Laser Surgery

Length of Hospitalization

Positive Bacterial Infection From a Sterile Site

Intraventricular Hemorrhage

Detailed description: 362 subjects were randomized to the study at 33 US sites. Final study visits of Month 18-22 corrected age long term follow up were completed. Study database is locked.

Eligibility

Minimum age: N/A. Maximum age: 5 Days. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Informed consent from the legally authorized representative.

- > 48 hours of age and < 120 hours old at time of first drug administration

- < 750 g birth weight

- Negative blood cultures for Candida

Exclusion Criteria:

- History of a hypersensitivity or severe vasomotor reaction to any azole

- receiving antifungal therapy for suspected/proven invasive fungal infection

- medical condition, in the opinion of the Investigator, may create an unacceptable

additional risk

- diagnosed with invasive candidiasis or congenital Candida infection.

- liver failure (AST and ALT > 250 U/L)

- renal failure (creatinine > 2 mg/dL)

- major lethal congenital or genetic anomalies

- triplet or higher multiple gestations

Locations and Contacts

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

Additional Information

Starting date: November 2008
Last updated: July 27, 2014

Page last updated: August 20, 2015

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