Glutamine Supplementation to Prevent Death or Infection in Extremely Premature Infants - Full Text View

Purpose

This large multicenter double-masked clinical trial tested whether supplementation of standard neonatal parenteral nutrition with glutamine would reduce the risk of death or late-onset sepsis in extremely-low-birth-weight (ELBW, less than or equal to 1000 gm) infants. Neonates with birth weights of 401-1000gm were randomized to standard TrophAmine or TrophAmine supplemented with glutamine before 72 hours and continued until the infants are tolerating full enteral feedings.

Condition	Intervention	Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Sepsis	Drug: Glutamine Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Randomized Controlled Trial of Parenteral Glutamine Supplementation for Extremely-Low-Birth-Weight (ELBW) Infants

Resource links provided by NLM:

MedlinePlus related topics: Birth Weight Premature Babies Sepsis

Drug Information available for: Glutamine Amino acids

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:

Death or late-onset sepsis [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tolerance of enteral feeding (number of days to reach full enteral feeds) and decrease number of episodes of feeding intolerance [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
Necrotizing Enterocolitis [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
Episodes of late-onset sepsis [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
Growth (days to reach 1500 grams) [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
Number of days on parenteral nutrition [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
Length of stay in NICU [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
Neurodevelopmental outcome [ Time Frame: 18-22 months corrrected age ] [ Designated as safety issue: Yes ]
Levels of pro-inflammatory cytokines [ Time Frame: In the perinatal period ] [ Designated as safety issue: No ]

Enrollment:	1433
Study Start Date:	July 1999
Study Completion Date:	August 2001
Primary Completion Date:	December 2000 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Glutamine TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) with L-glutamine added (20% of the total amount of amino acids)	Drug: Glutamine Infants randomized to glutamine supplementation will receive glutamine any time that parenteral nutrition is required during the first 120 days of hospitalization. Other Names: L-Glutamine TrophAmine
Placebo Comparator: Placebo Standard TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids)	Drug: Placebo TrophAmine given any time that parenteral nutrition is required during the first 120 days of hospitalization. Other Name: TrophAmine

Detailed Description:

Meeting the protein and energy requirements of extremely premature infants in early postnatal life requires early hyperalimentation and the gradual introduction of enteral feedings. Glutamine, which is the most abundant amino acid in the human body and taken up in greatest quantity by the fetus from the placenta, is not routinely provided in neonatal parenteral nutrition preparations.

This large multicenter double-masked clinical trial tested whether supplementation of standard neonatal parenteral nutrition with glutamine would reduce the risk of death or late-onset sepsis in extremely-low-birth-weight (ELBW, less than or equal to 1000 gm) infants. Neonates with birth weights of 401-1000gm were randomized to standard TrophAmine or TrophAmine supplemented with glutamine before 72 hours and continued until the infants are tolerating full enteral feedings.

Infants received a neurodevelopmental assessment by masked, certified examiners at 18-22 months postmenstrual age.

Eligibility

Ages Eligible for Study:	up to 72 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

401-1000 gm
More than 12 hrs and less than 72 hrs after birth; intravenous access
Parental consent

Exclusion Criteria:

One or more major congenital anomalies
Infants meeting criteria for terminal illness
Congenital nonbacterial infection with overt signs at birth

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005775

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, 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, North Carolina
RTI International
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030

Sponsors and Collaborators

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

National Center for Research Resources (NCRR)

Investigators

Principal Investigator:	Brenda B. Poindexter, MD MS	Indiana University
Principal Investigator:	Waldemar A. Carlo, MD	University of Alabama at Birmingham
Principal Investigator:	Neil N. Finer, MD	University of California, San Diego
Principal Investigator:	Avroy A. Fanaroff, MD	Case Western Reserve University
Principal Investigator:	Edward F. Donovan, MD	Cincinnati Children's Medical Center
Principal Investigator:	Barbara J. Stoll, MD	Emory University
Principal Investigator:	Charles R. Bauer, MD	University of Miami
Principal Investigator:	Lu-Ann Papile, MD	University of New Mexico
Principal Investigator:	W. Kenneth Poole, PhD	RTI International
Principal Investigator:	David K. Stevenson, MD	Stanford University
Principal Investigator:	Sheldon B. Korones, MD	University of Tennessee
Principal Investigator:	Jon E. Tyson, MD MPH	The University of Texas Health Science Center, Houston
Principal Investigator:	Abbot R. Laptook, MD	University of Texas Southwestern Medical Center
Principal Investigator:	Seetha Shankaran, MD	Wayne State University
Principal Investigator:	William Oh, MD	Women and Infants Hospital, Brown University
Principal Investigator:	Richard A. Ehrenkranz, MD	Yale University

More Information

Additional Information:

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

Click here for the Cochrane review "Glutamine supplementation for preventionof morbidity in the preterm infant." This link exits the ClinicalTrials.gov site

NICHD Pregnancy & Perinatology Branch This link exits the ClinicalTrials.gov site

Publications:

Poindexter BB, Ehrenkranz RA, Stoll BJ, Koch MA, Wright LL, Oh W, Papile LA, Bauer CR, Carlo WA, Donovan EF, Fanaroff AA, Korones SB, Laptook AR, Shankaran S, Stevenson DK, Tyson JE, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network. Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants. Am J Clin Nutr. 2003 Mar;77(3):737-43.

Poindexter BB, Ehrenkranz RA, Stoll BJ, Wright LL, Poole WK, Oh W, Bauer CR, Papile LA, Tyson JE, Carlo WA, Laptook AR, Narendran V, Stevenson DK, Fanaroff AA, Korones SB, Shankaran S, Finer NN, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network. Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants. Pediatrics. 2004 May;113(5):1209-15.

Oh W, Poindexter BB, Perritt R, Lemons JA, Bauer CR, Ehrenkranz RA, Stoll BJ, Poole K, Wright LL; Neonatal Research Network. Association between fluid intake and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants. J Pediatr. 2005 Dec;147(6):786-90.

Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA; National Institute of Child Health and Human Development Neonatal Research Network. Early provision of parenteral amino acids in extremely low birth weight infants: relation to growth and neurodevelopmental outcome. J Pediatr. 2006 Mar;148(3):300-305.

Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Wright LL, Langer JC, Poole WK; NICHD Neonatal Research Network. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics. 2006 Jul;118(1):e115-23.

Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Higgins RD, Langer JC, Poole WK; National Institute of Child Health and Human Development National Research Network. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics. 2007 Oct;120(4):e953-9.

Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF. Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death. J Perinatol. 2009 Jan;29(1):57-62. Epub 2008 Aug 21.

Peralta-Carcelen M, Moses M, Adams-Chapman I, Gantz M, Vohr BR; NICHD Neonatal Research Network; National Institutes of Health. Stability of neuromotor outcomes at 18 and 30 months of age after extremely low birth weight status. Pediatrics. 2009 May;123(5):e887-95.

Responsible Party:	Brenda B. Poindexter, Lead Principal Investigator, Indiana University
ClinicalTrials.gov Identifier:	NCT00005775 History of Changes
Other Study ID Numbers:	NICHD-NRN-0020, U10HD027856, U10HD021364, U10HD034216, U10HD034167, U10HD021397, U10HD027853, U10HD027871, U10HD021415, U10HD027904, U10HD027881, U10HD021385, U10HD027851, U10HD027880, U10HD021373, U01HD036790, M01RR008084, M01RR006022, M01RR000750, M01RR000997, M01RR000070, M01RR001032
Study First Received:	June 1, 2000
Last Updated:	January 9, 2011
Health Authority:	United States: Federal Government United States: Institutional Review Board United States: Food and Drug Administration

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

NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW) infants
Prematurity
Glutamine

Total parenteral nutrition
Nutrition
Very low birth weight (VLBW) infants

Additional relevant MeSH terms:

Birth Weight
Sepsis
Body Weight
Signs and Symptoms

Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on June 17, 2013