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

This study has been completed.
Sponsor:
Information provided by:
Prolacta Bioscience
ClinicalTrials.gov Identifier:
NCT00506584
First received: July 20, 2007
Last updated: February 16, 2010
Last verified: February 2010
  Purpose

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.


Condition Intervention
Infant, Very Low Birth Weight
Dietary Supplement: Pasteurized human milk and pasteurized human milk fortifier
Dietary Supplement: Human milk fortifier (bovine-based), pre-term formula
Dietary Supplement: Pre-term/term formula

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Randomized Study of Human Milk-Based Versus Bovine-based Nutrition for Very Low Birth Weight Pre-Term Infants

Resource links provided by NLM:


Further study details as provided by Prolacta Bioscience:

Primary Outcome Measures:
  • The primary measure of efficacy for the study is the number of days of TPN (total parenteral nutrition) [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Weight gain and other measures of growth including length and head circumference [ Time Frame: The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first ] [ Designated as safety issue: No ]
  • Daily amount of all nutrition [ Time Frame: The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first ] [ Designated as safety issue: No ]
  • Time to discharge from the NICU and hospital [ Time Frame: The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first ] [ Designated as safety issue: No ]
  • Frequency of occurrence of late-onset sepsis and necrotizing enterocolitis [ Time Frame: The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first ] [ Designated as safety issue: Yes ]
  • Frequency of feeding intolerance [ Time Frame: The first 90 days of life, transfer to non-study institution, or initiation of 50% oral feeding, whichever comes first ] [ Designated as safety issue: Yes ]

Enrollment: 260
Study Start Date: July 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1, arm 1
Human breast milk + Prolact20/Neo20 (as needed) + Prolact+4 (initiated when nutrition volume reaches 100 mL/kg/day, where Prolact20/Neo 20 are donor human milk formulations at 20 cal/oz, Prolact+4 is a human-milk derived human milk fortified designed to add 4 cal/oz to 20 cal/oz human breast milk.
Dietary Supplement: Pasteurized human milk and pasteurized human milk fortifier
Human milk fortifier is initiated when nutrition volume reaches 100 mL/kg/day
Other Names:
  • Prolact20/Neo20
  • Prolact+4
Experimental: Group1, Arm 2
Human breast milk + Prolact20/Neo20 (as needed) + Prolact+4 (initiated when nutrition volume reaches 40 mL/kg/day), where Prolact20/Neo 20 are donor human milk formulations at 20 cal/oz, Prolact+4 is a human-milk derived human milk fortified designed to add 4 cal/oz to 20 cal/oz human breast milk.
Dietary Supplement: Pasteurized human milk and pasteurized human milk fortifier
Human milk fortifier is initiated when nutrition volume reaches 40 mL/kg/day
Other Names:
  • Prolact20/Neo 20
  • Prolact+4
Active Comparator: Group 1, Arm 3
Human breast milk + bovine-based human milk fortifier (initiated when nutrition volume reaches 100 mL/kg/day) + pre-term formula (as needed)
Dietary Supplement: Human milk fortifier (bovine-based), pre-term formula
Bovine-based human milk fortifier is initiated when nutrition volume reaches 100 mL/kg/day
Experimental: Group 2, Arm 1
Prolact20/Neo20 + Prolact+4 (initiated when nutrition volume reaches 100 mL/kg/day), where Prolact20/Neo 20 are donor human milk formulations at 20 cal/oz, Prolact+4 is a human-milk derived human milk fortified designed to add 4 cal/oz to 20 cal/oz human breast milk.
Dietary Supplement: Pasteurized human milk and pasteurized human milk fortifier
Human milk fortifier initiated when nutrition volume reaches 100 mL/kg/day
Other Names:
  • Prolact20/Neo20
  • Prolact+4
Active Comparator: Group 2, Arm 2
Pre-term/term formula (minimum 20 cal/oz)
Dietary Supplement: Pre-term/term formula
Bovine milk-derived nutrition formulated for very low birth weight infants

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 21 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00506584

Locations
United States, California
Alta Bates Summit Medical Center
Berkeley, California, United States, 94705
University of California, San Diego Medical Center
San Diego, California, United States, 92103-8774
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
Shands Children's Hospital
Gainesville, Florida, United States, 32610-0296
United States, Illinois
Rush-Presbyterian St. Luke's Medical Center
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, New York
Schneider Children's Hospital at North Shore
Manhasset, New York, United States, 11030
Strong Memorial Hospital
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Texas
Ben Taub Hospital/Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Health Science Center
San Antonio, Texas, United States, 78229-3900
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
Austria
Innsbruck Children's Hospital
Innsbruck, Austria, A-6020
Sponsors and Collaborators
Prolacta Bioscience
Investigators
Study Chair: Richard J Schanler, MD Schneider Children's Hospital at North Shore
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Martin L. Lee, PhD; Chief Scientific Officer, Prolacta Bioscience, Inc.
ClinicalTrials.gov Identifier: NCT00506584     History of Changes
Other Study ID Numbers: MPPF 001-2007
Study First Received: July 20, 2007
Last Updated: February 16, 2010
Health Authority: Austria: Ethikkommission
United States: Institutional Review Board

Keywords provided by Prolacta Bioscience:
Human milk nutritional intervention
Pre-term, very low birth weight
Fortification of human breast milk

Additional relevant MeSH terms:
Birth Weight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 28, 2014