Randomized Study of Human-Milk Based Nutrition Versus Formula in Premature Infants

Infant, Very Low Birth Weight Clinical Trial

Official title:

A Randomized Study of Human Milk-Based Versus Bovine-based Nutrition for Very Low Birth Weight Pre-Term Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00506584
• Other study ID #: MPPF 001-2007
• Status: Completed
• Phase: N/A
• First received: July 20, 2007
• Last updated: February 16, 2010
• Start date: July 2007
• Est. completion date: July 2008

Study information

• Verified date: February 2010
• Source: Prolacta Bioscience
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: EthikkommissionUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether very low birth weight infants (less than or equal to 1250g or about 2 3/4 pounds) born prematurely fed a diet of only human milk and human milk-derived nutrition have better health outcomes than babies fed at least some formula (made from cow's milk)or formula-derived nutrition.

Description:

The goal of this study is to evaluate the short-term effect (up to 90 days of life) of purely human-based nutrition using mother's own milk (when available), donor milk preparations and a human-based fortifier (Prolact+4) as needed when compared with mother's own milk supplemented with pre-term formula and using a bovine-based HMF (as needed for fortification of mother's own milk), i.e. "Study Group 1"; or, when mother's milk is not available, comparing the use of donor milk (plus human milk based fortification) with pre-term/term formula, i.e. "Study Group 2". In both instances the comparison will be based on the primary endpoint of days of TPN, and on parameters such as time to full enteral feeding (approximately 150-160 mL/kg/day), amount of IV fluid support, culture-proven sepsis, NEC, death, growth and short-term development, cultured-proven sepsis and incidence of feeding intolerance in either a 2-arm (human nutrition versus bovine nutrition: "Study Group 2") or 3-arm randomized design (human fortifier given when feedings reach 40 mL/kg/day, human fortifier given when feedings reach 100 mL/kg/day, and bovine-based HMF given when feedings reach 100 mL/kg/day [or pre-term formula if mother's milk is not available]: "Study Group 1").

Statistically, the study will attempt to evaluate a null hypothesis of equivalent results with respect to these parameters between either the three types of fortifications in "Study Group 1" or the two types of overall nutrition in "Study Group 2", as compared with an alternative of some inequality between the groups, i.e. letting μ be the mean number of days of TPN any of the study arms, then for "Study Group 1 the hypotheses may be written as:

H0: μ control = μ human 40 = μhuman 100 and HA: At least two of μ control, μ human 40, and μhuman 100 are not equal, where "control" is the bovine-based HMF group, "human 40" is the human fortifier group starting at 40 mL/kg/day (arm 2) and "human 100" is the human fortifier group starting at 100 mL/kg/day (arm 1). For "Study Group 2", the competing hypotheses are: H0: μ formula = μ human and HA: μ formula ≠ μ human , where "formula" is the pre-term/term formula group and "human" is the human-based (donor milk/human-based fortifier) group.

In addition, data will be collected on overall survival and length of stay in the NICU. Any baby that does not complete the full study period will be right-censored in this regard for the purposes of data evaluation. For centers that obtain long-term follow up (18-24 months) on their patients, data on developmental outcomes will be evaluated as available.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Days

Eligibility

Inclusion Criteria:

1. Birth weight between 500 and 1250g.

2. Have a reasonable expectation of survival for the maximum 90 day duration of the study.

3. In "Study Group 1", must be able to adhere to a feeding protocol involving mother's own milk and that may include donor human milk with fortification using a human-based product (Prolact+4) or fortification with a bovine-based human milk fortifier and the use of a pre-term/term formula; or in "Study Group 2" the use of donor human milk with Prolact+4 or a pre-term/term formula from the time that the infant initiates enteral feeding through day 90 of life, until discharge from the study institution, discharge home, death or the initiation of at least 50% total oral nutrition (4 complete feeds in a 24 hour period), whichever comes first.

4. Enteral feeding must begin before the 21st day of life.

5. Total parenteral nutrition (TPN) initiated within 48 hours after birth.

6. Informed consent obtained from parent or legal guardian.

Exclusion Criteria:

1. Less than a reasonable expectation of survival for the infant's particular gestational age through the study period (first 90 days of life, discharge to a non-study institution, discharge home, death or initiation of 50% oral nutrition, whichever comes first).

2. On any other clinical study affecting nutritional management during the study period.

3. Decision to not start minimum enteral feed before day 21 of life.

4. Decision to not start TPN within the first 48 hours after birth.

5. Unable to obtain informed consent from parent or legal guardian prior to the initiation of enteral feeding.

6. Presence of clinically significant congenital heart disease.

7. Presence of any major congenital malformations.

8. Reasonable potential for early transfer to a non-study institution.

9. Unable to participate for any reason based on the decision of the study investigator.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Birth Weight
• Infant, Very Low Birth Weight

Intervention

Dietary Supplement:
• Pasteurized human milk and pasteurized human milk fortifier
Human milk fortifier is initiated when nutrition volume reaches 100 mL/kg/day
• Pasteurized human milk and pasteurized human milk fortifier
Human milk fortifier is initiated when nutrition volume reaches 40 mL/kg/day
• Human milk fortifier (bovine-based), pre-term formula
Bovine-based human milk fortifier is initiated when nutrition volume reaches 100 mL/kg/day
• Pasteurized human milk and pasteurized human milk fortifier
Human milk fortifier initiated when nutrition volume reaches 100 mL/kg/day
• Pre-term/term formula
Bovine milk-derived nutrition formulated for very low birth weight infants

Locations

Country	Name	City	State
Austria	Innsbruck Children's Hospital	Innsbruck
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Alta Bates Summit Medical Center	Berkeley	California
United States	Rush-Presbyterian St. Luke's Medical Center	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Shands Children's Hospital	Gainesville	Florida
United States	Ben Taub Hospital/Baylor College of Medicine	Houston	Texas
United States	Schneider Children's Hospital at North Shore	Manhasset	New York
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Strong Memorial Hospital	Rochester	New York
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	University of Texas Health Science Center	San Antonio	Texas
United States	University of California, San Diego Medical Center	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Prolacta Bioscience

Countries where clinical trial is conducted

United States,  Austria, 

References & Publications (1)

Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawöger R, Kiechl-Kohlendorfer U, Chan GM, Blanco CL, Abrams S, Cotten CM, Laroia N, Ehrenkranz RA, Dudell G, Cristofalo EA, Meier P, Lee ML, Rechtman DJ, Lucas A. An exclusively human milk-based diet is associa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary measure of efficacy for the study is the number of days of TPN (total parenteral nutrition)		The first 90 days of life, discharge from the study institution or initiation of 50% oral nutrition (50% of the feeding volume in a given 24 hour period provided PO, or 4 complete PO feeds in a given 24 hour period), whichever comes first	No
Secondary	Weight gain and other measures of growth including length and head circumference		The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first	No
Secondary	Daily amount of all nutrition		The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first	No
Secondary	Time to discharge from the NICU and hospital		The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first	No
Secondary	Frequency of occurrence of late-onset sepsis and necrotizing enterocolitis		The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first	Yes
Secondary	Frequency of feeding intolerance		The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first	Yes