Early Diagnosis of Candidiasis in Premature Infants

Infection Clinical Trial

— Candida  

Official title:

Early Diagnosis of Nosocomial Candidiasis Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00109525
• Other study ID #: NICHD-NRN-0030
• Secondary ID: UL1RR024139UL1RR
• Status: Completed
• Start date: March 2004
• Est. completion date: December 2009

Study information

• Verified date: March 2019
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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. Surviving study subjects completed a neurodevelopmental evaluation at 18-22 months corrected age.

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.

Surviving study subjects completed a neurodevelopmental evaluation at 18-22 months corrected age to evaluate potential early risk factors with long-term outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1500
• Est. completion date: December 2009
• Est. primary completion date: July 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 120 Days

Eligibility

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

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Wake Forest University	Charlotte	North Carolina
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of California at San Diego	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Adams-Chapman I, Bann CM, Das A, Goldberg RN, Stoll BJ, Walsh MC, Sánchez PJ, Higgins RD, Shankaran S, Watterberg KL, Duara S, Miller NA, Heyne RJ, Peralta-Carcelen M, Goldstein RF, Steichen JJ, Bauer CR, Hintz SR, Evans PW, Acarregui MJ, Myers GJ, Vohr B — View Citation

Benjamin DK Jr, Stoll BJ, Gantz MG, Walsh MC, Sánchez PJ, Das A, Shankaran S, Higgins RD, Auten KJ, Miller NA, Walsh TJ, Laptook AR, Carlo WA, Kennedy KA, Finer NN, Duara S, Schibler K, Chapman RL, Van Meurs KP, Frantz ID 3rd, Phelps DL, Poindexter BB, Be — View Citation

Bliss JM, Wong AY, Bhak G, Laforce-Nesbitt SS, Taylor S, Tan S, Stoll BJ, Higgins RD, Shankaran S, Benjamin DK Jr; Candida Subcommittee of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Candi — View Citation

Greenberg RG, Benjamin DK Jr, Gantz MG, Cotten CM, Stoll BJ, Walsh MC, Sánchez PJ, Shankaran S, Das A, Higgins RD, Miller NA, Auten KJ, Walsh TJ, Laptook AR, Carlo WA, Kennedy KA, Finer NN, Duara S, Schibler K, Ehrenkranz RA, Van Meurs KP, Frantz ID 3rd, — View Citation

Wynn JL, Tan S, Gantz MG, Das A, Goldberg RN, Adams-Chapman I, Stoll BJ, Shankaran S, Walsh MC, Auten KJ, Miller NA, Sánchez PJ, Higgins RD, Cotten CM, Smith PB, Benjamin DK Jr; NICHD Neonatal Research Network. Outcomes following candiduria in extremely l — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probability of invasive candidiasis based on new assay results		Until discharge
Primary	Determine test performance of clinical predictive model		Until discharge
Secondary	Determine test performance (sensitivity and specificity) of polymerase chain reaction (PCR) testing		Until discharge
Secondary	Determine test performance of Beta-glucan assay		Until discharge
Secondary	Determine test performance of Gas Chromatography Mass Spectrometry for D-arabinitol of blood samples		Until discharge
Secondary	Determine test performance of Gas Chromatography Mass Spectrometry for D-arabinitol of urine samples		Until discharge
Secondary	Determine test performance of the blood culture		Until discharge
Secondary	Determine test performance of the lumbar puncture (cell count, protein, glucose, and culture)		Until discharge
Secondary	Determine test performance of tracheal aspirates		Until discharge
Secondary	Determine test performance of urine cultures		Until discharge
Secondary	Compare clinical predictive model performance to neonatologist clinical judgment		Until discharge
Secondary	Determine incidence of end-organ damage in neonates with candidemia		Until discharge
Secondary	Determine resistance patterns of organisms isolated		Until discharge
Secondary	Determine molecular epidemiology of candidemia		Until discharge
Secondary	Determine genetic expression of organism virulence factors		Until discharge
Secondary	Neurodevelopmental outcome		18-22 months corrected age

External Links

•   NICHD Neonatal Research Network