Early Diagnosis of Candidiasis in Premature Infants - Full Text View

Sponsored by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00109525

Purpose

This observational study evaluated the performance of new lab tests in detecting candida species fungal infections in extremely low birth weight (ELBW) infants quickly and accurately. 19 NICHD Neonatal Research Network sites enrolled 1,500 infants with birth weights ≤1,000g; 100 of these infants later tested positive for candidiasis. Blood, urine, and lumbar puncture samples were collected whenever other specimens were obtained from participants for cultures. These samples are being tested using the new methods and compared with standard culture results. In addition, this study will evaluate long-term outcomes of patients with invasive candidiasis, with study subjects completing a neurodevelopmental evaluation at 18-22 months corrected age.

Condition
Infection Candida Candidiasis Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature

Study Type:	Observational
Study Design:	Cohort, Prospective
Official Title:	Early Diagnosis of Nosocomial Candidiasis Study

Resource links provided by NLM:

MedlinePlus related topics: Fungal Infections Premature Babies Urine and Urination Yeast Infections

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Probability of invasive candidiasis based on new assay results [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of clinical predictive model [ Time Frame: Until discharge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine test performance (sensitivity and specificity) of polymerase chain reaction (PCR) testing [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of Beta-glucan assay [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of Gas Chromatography Mass Spectrometry for D-arabinitol of blood samples [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of Gas Chromatography Mass Spectrometry for D-arabinitol of urine samples [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of the blood culture [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of the lumbar puncture (cell count, protein, glucose, and culture) [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of tracheal aspirates [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine test performance of urine cultures [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Compare clinical predictive model performance to neonatologist clinical judgment [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine incidence of end-organ damage in neonates with candidemia [ Time Frame: Until discharge ] [ Designated as safety issue: Yes ]
Determine resistance patterns of organisms isolated [ Time Frame: Until discharge ] [ Designated as safety issue: Yes ]
Determine molecular epidemiology of candidemia [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Determine genetic expression of organism virulence factors [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
Neurodevelopmental outcome [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]

Biospecimen Retention: None Retained

Biospecimen Description:

Enrollment:	1500
Study Start Date:	March 2004
Estimated Study Completion Date:	July 2009
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Candida species are a leading cause of infectious mortality in newborns with the incidence rates estimated at 4-18% in extremely low birth weight (ELBW) infants. 20-30% of these infants are likely to die. Because candida can invade virtually all body tissues (eyes, brain, heart, lung, liver, spleen, urinary tract, and joints), survivors of invasive Candida infections are at risk of blindness, developmental delays, and the need for surgical and other corrective procedures.

Time is of the essence in detecting and treating these infections, with infant mortality from candidiasis largely attributed to duration of time for cultures to become positive for Candida. Diagnosis of candidiasis is challenging - blood and urine tests are slow (taking up to 72 hours to complete) and inaccurate in many cases, showing negative results despite overwhelming disease in adults as well as children. These problems are likely made worse in neonates, with smaller amounts of blood available for testing and infections that often spread to tissues inaccessible for testing.

This observational study is evaluating the performance of new lab tests (beta-glucan assays, Gas Chromatography Mass Spectrometry for D-arabinitol, and polymerase chain reaction tests) compared to existing culture tests in detecting candida species fungal infections in extremely low birth weight (ELBW) infants quickly and accurately.

In this study, 19 NICHD Neonatal Research Network sites enrolled 1,500 infants with birth weights ≤1,000g by 72 hours of life; more than 100 of these infants later tested positive for candidiasis. In the larger cohort, whenever cultures of blood or urine were obtained, or a lumbar puncture was done, additional samples and clinical data were collected. These additional samples are being tested using the new techniques under investigation. No additional blood specimens were taken once participants had a positive blood culture for candida. Note: Test procedure reagents are being provided the Duke University laboratory by Cape Cod Incorporated and Rockeby; the Thrasher Research Fund is also providing support to the Duke University laboratory.

Study subjects will complete a neurodevelopmental evaluation at 18-22 months corrected age to evaluate potential early risk factors with long-term outcome.

Eligibility

Ages Eligible for Study:	up to 120 Days
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

Infants with birth weights ≤1,000 grams

Criteria

Inclusion Criteria:

Infants born ≤1,000g birth weight
Infants >72 hours old and less than 120 days old

Exclusion Criteria:

Prior positive blood culture for Candida
Evidence of congenital candidiasis
Parents/legal guardians refuse consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00109525

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
University of California at San Diego
San Diego, California, United States, 92103-8774
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
RTI International
Durham, North Carolina, United States, 27705
Wake Forest University
Charlotte, North Carolina, United States, 27157
United States, Ohio
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
University of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:	Abbot R. Laptook, MD	Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator:	Michele C. Walsh, MD MS	Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator:	Ronald N. Goldberg, MD	Duke University
Principal Investigator:	Barbara J. Stoll, MD	Emory University
Principal Investigator:	Brenda B. Poindexter, MD MS	Indiana University
Principal Investigator:	Abhik Das, PhD	RTI International
Principal Investigator:	Krisa P. Van Meurs, MD	Stanford University
Principal Investigator:	Ivan D. Frantz III, MD	Tufts Medical Center
Principal Investigator:	Waldemar A. Carlo, MD	University of Alabama at Birmingham
Principal Investigator:	Neil N. Finer, MD	University of California, San Diego
Principal Investigator:	Kurt Schibler, MD	University of Cincinnati
Principal Investigator:	Edward F. Bell, MD	University of Iowa
Principal Investigator:	Shahnaz Duara, MD	University of Miami
Principal Investigator:	Kristi L. Watterberg, MD	University of New Mexico
Principal Investigator:	Dale L. Phelps, MD	University of Rochester
Principal Investigator:	Kathleen A. Kennedy, MD MPH	The University of Texas Health Science Center, Houston
Principal Investigator:	Pablo J. Sanchez, MD	University of Texas Southwestern Medical Center at Dallas
Principal Investigator:	T. Michael O'Shea, MD MPH	Wake Forest University
Principal Investigator:	Seetha Shankaran, MD	Wayne State University
Principal Investigator:	Richard A. Ehrenkranz, MD	Yale University

More Information

Additional Information:

NICHD Neonatal Research Network This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Duke University ( Daniel K. Benjamin, Jr., Lead Principal Investigator )
Study ID Numbers:	NICHD-NRN-0028, CCTS KL2 RR24149 (Houston), CCTS UL1 RR24128 (Duke), CCTS UL1 RR24139 (Yale), CCTS UL1 RR24148 (Houston), CCTS UL1 RR24160 (Rochester), GCRC M01 RR16587 (Miami), GCRC M01 RR2588 (Houston), GCRC M01 RR30 (Duke), GCRC M01 RR32 (Alabama), GCRC M01 RR39 (Emory), GCRC M01 RR44 (Rochester), GCRC M01 RR54 (Tufts), GCRC M01 RR59 (Iowa), GCRC M01 RR6022 (Yale), GCRC M01 RR633 (Dallas), GCRC M01 RR70 (Stanford), GCRC M01 RR7122 (Wake), GCRC M01 RR750 (Indiana), GCRC M01 RR80 (Case), GCRC M01 RR8084 (Cinn), GCRC M01 RR997 (New Mexico), U01 HD36790 (RTI), U10 HD21364 (Case), U10 HD21373 (Houston), U10 HD21385 (Wayne), U10 HD21397 (Miami), U10 HD27851 (Emory), U10 HD27853 (Cinn), U10 HD27856 (Indiana), U10 HD27871 (Yale), U10 HD27880 (Stanford), U10 HD27904 (Brown), U10 HD34216 (Alabama), U10 HD40461 (UCSD), U10 HD40492 (Duke), U10 HD40498 (Wake), U10 HD40521 (Rochester), U10 HD40689 (Dallas), U10 HD53089 (New Mexico), U10 HD53109 (Iowa), U10 HD53119 (Tufts)
Study First Received:	April 28, 2005
Last Updated:	April 1, 2009
ClinicalTrials.gov Identifier:	NCT00109525 History of Changes
Health Authority:	United States: Federal Government; United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

NICHD Neonatal Research Network
Fungal Infection
Mycosis
Extremely Low Birth Weight (ELBW)
Prematurity

Clinical Judgement
Polymerase chain reaction (PCR) testing
Beta-glucan assay
Mass Spectrometry
Lumbar puncture

Study placed in the following topic categories:

Body Weight
Birth Weight
Signs and Symptoms

Mycoses
Candidiasis
Torulopsis

Additional relevant MeSH terms:

Body Weight
Birth Weight
Mycoses

Signs and Symptoms
Candidiasis
Infection

ClinicalTrials.gov processed this record on September 03, 2009