AzTrials
AzTrials

CandidiasisPhase 3NCT00734539

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

A Phase 3 study testing fluconazole in people with Candidiasis, run by Daniel Benjamin at 33 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 2 to 5 days
Conditions the study is for
Candidiasis
What is being tested?
fluconazole
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
362 participants
Where
33 sitesUnited States
Study dates
Nov 2008to Apr 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 5 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United States33 sites

  • Akron Children's Hospital

    Akron, Ohio, 44313

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Brookdale University Medical Center

    Brooklyn, New York, 11203

  • Kings County Hospital Center

    Brooklyn, New York, 11203

  • SUNY Dowstate Medical Center

    Brooklyn, New York, 11203

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • Wayne State University

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Cooks Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32610

  • University of Texas Medical Branch

    Galveston, Texas, 77555

  • Pitt County Memorial Hospital

    Greenville, North Carolina, 27834

  • Texas Children's Hospital/Baylor College of Medicine

    Houston, Texas, 77030

  • University of Texas - Houston

    Houston, Texas, 77030

  • Riley Hospital

    Indianapolis, Indiana, 46601

  • Baptist Medical Center

    Jacksonville, Florida, 32209

  • Shands Jacksonville Medical Center

    Jacksonville, Florida, 32209

  • University of Nevada School of Medicine

    Las Vegas, Nevada, 89109

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72202

  • Arkansas Childrens Hospital

    Little Rock, Arkansas, 72205

  • Kosair Children's Hospital

    Louisville, Kentucky, 40202

  • University of Tennessee

    Memphis, Tennessee, 38130

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota, Fairview Medical Center

    Minneapolis, Minnesota, 55455

  • Tulane University School of Medicine

    New Orleans, Louisiana, 70112

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19107

  • Oregon Health Sciences Center

    Portland, Oregon, 97201

  • University of California-San Diego

    San Diego, California, 92103

  • Memorial Hospital

    South Bend, Indiana, 46601

  • West Jersey Hospital - Voorhees

    Voorhees Township, New Jersey, 08043

  • Wesley Medical Center

    Wichita, Kansas, 67214

Other trials in United States

About this study

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

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.

Read more

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.

Read the 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.

Conditions
Candidiasis
Being tested
fluconazole, placebo
Keywords
Candida, Neonate, Fluconazole, Prophylaxis, Colonization, Resistance
Medical subject headings
Candidiasis, Torulopsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fluconazoleDrug

    Also called Diflucan

    6mg/kg IV/PO twice weekly for a total of up to 12-13 doses

  • placeboDrug

    normal saline (IV) or 3 parts Ora Plus oral suspension vehicle and 1 part simethicone suspension (PO): will be given twice weekly PO/IV for a total of up to 12-13 doses

Study groups in NCT00734539
Study groupRoleWhat they receive
1Experimentalfluconazole 6mg/kg IV or PO twice weekly for 6 weeks
Receives: Drug: fluconazole
2Placebo comparatorPlacebo IV or PO twice weekly for 6 weeks
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Death or Candidiasis

    The primary endpoint for the study is death or candidiasis.

    1. Death prior to study day 49.
    2. Candidiasis prior to study day 49
    3. Definite: isolation of Candida from normally sterile body fluid (blood, CSF, urine [obtained via sterile catheterization or suprapubic tap], peritoneal fluid).
    4. Probable:
    5. > 5 days of consecutive antifungal therapy AND both: ii. Thrombocytopenia <150,000/mm3 iii. Positive Candida culture from nonsterile site (ETS, bag urine)

    Measured: study day 49

Secondary outcomes (11)

  1. Neurodevelopmental Impairment

    Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy

    Measured: 18-22 months corrected gestational age

  2. Candidiasis

    Definite or probable

    Measured: prior to hospital discharge, up to 15 ½ months

  3. Stage II or Higher Necrotizing Enterocolitis

    Measured: prior to hospital discharge, up to 15 ½ months

  4. Focal Intestinal Perforation

    Measured: prior to hospital discharge, up to 15 ½ months

  5. Chronic Lung Disease

    Measured: 36 weeks corrected gestational age

  6. Patent Ductus Arterious Requiring Surgical Ligation

    Measured: prior to hospital discharge, up to 15 ½ months

  7. Periventricular Leukomalacia

    Measured: prior to hospital discharge, up to 15 ½ months

  8. Retinopathy of Prematurity Requiring Laser Surgery

    Measured: prior to hospital discharge, up to 15 ½ months

  9. Length of Hospitalization

    Measured: prior to hospital discharge, up to 15 ½ months

  10. Positive Bacterial Infection From a Sterile Site

    Measured: prior to hospital discharge, up to 15 ½ months

  11. Intraventricular Hemorrhage

    Grade 3 or 4

    Measured: prior to hospital discharge, up to 15 ½ months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionDec 2011
  4. Study completionApr 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
362 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00734539
Sponsor's protocol ID
Pro00001538
Other IDs
1R01HD057956-01, Pro00017720
Status last verified
Feb 2019
First submitted
13 Aug 2008
Last updated
1 Mar 2019
Data monitoring committee
Yes
Individual data sharing
Yes: In December 2018, after receiving IRB's approval, the team submitted the de-identified study dataset and redacted study documents to the NICHD Data and Specimen Hub (DASH).

Publications

  • Benjamin DK Jr, Hudak ML, Duara S, Randolph DA, Bidegain M, Mundakel GT, Natarajan G, Burchfield DJ, White RD, Shattuck KE, Neu N, Bendel CM, Kim MR, Finer NN, Stewart DL, Arrieta AC, Wade KC, Kaufman DA, Manzoni P, Prather KO, Testoni D, Berezny KY, Smith PB; Fluconazole Prophylaxis Study Team. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial. JAMA. 2014 May 7;311(17):1742-9. doi: 10.1001/jama.2014.2624.

    PubMed 24794367

  • Moran C, Smith PB, Cohen-Wolkowiez M, Benjamin DK Jr. Clinical trial design in neonatal pharmacology: effect of center differences, with lessons from the Pediatric Oncology Cooperative Research experience. Clin Pharmacol Ther. 2009 Dec;86(6):589-91. doi: 10.1038/clpt.2009.175.

    PubMed 19915602

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing fluconazole in people with Candidiasis, run by Daniel Benjamin at 33 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death or Candidiasis (time frame: study day 49). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00734539, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in