Glutamine Supplementation to Prevent Death or Infection in Extremely Premature Infants

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Completed

CT.gov ID

NCT00005775

Collaborator

National Center for Research Resources (NCRR) (NIH)

1,433

Enrollment

Locations

Arms

Duration (Months)

95.5

Patients Per Site

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Sepsis	Drug: Glutamine Drug: Placebo	Phase 3

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

1433 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized Controlled Trial of Parenteral Glutamine Supplementation for Extremely-Low-Birth-Weight (ELBW) Infants

Study Start Date :

Jul 1, 1999

Actual Primary Completion Date :

Dec 1, 2000

Actual Study Completion Date :

Aug 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
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 Names: TrophAmine

Arm

Intervention/Treatment

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 Names:

TrophAmine

Outcome Measures

Primary Outcome Measures

Death or late-onset sepsis [At hospital discharge]

Secondary Outcome Measures

Tolerance of enteral feeding (number of days to reach full enteral feeds) and decrease number of episodes of feeding intolerance [At hospital discharge]
Necrotizing Enterocolitis [At hospital discharge]
Episodes of late-onset sepsis [At hospital discharge]
Growth (days to reach 1500 grams) [At hospital discharge]
Number of days on parenteral nutrition [At hospital discharge]
Length of stay in NICU [At hospital discharge]
Neurodevelopmental outcome [18-22 months corrrected age]
Levels of pro-inflammatory cytokines [In the perinatal period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 72 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	University of California at San Diego	San Diego	California	United States	92103-8774
4	Yale University	New Haven	Connecticut	United States	06504
5	University of Miami	Miami	Florida	United States	33136
6	Emory University	Atlanta	Georgia	United States	30303
7	Indiana University	Indianapolis	Indiana	United States	46202
8	Wayne State University	Detroit	Michigan	United States	48201
9	University of New Mexico	Albuquerque	New Mexico	United States	87131
10	RTI International	Durham	North Carolina	United States	27705
11	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
12	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
13	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
14	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
15	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

NICHD Neonatal Research Network
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, Children's Hospital Medical Center, Cincinnati
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