Evaluation of Prolact-Plus Human Milk Fortifier
Condition: Infant, Very Low Birth Weight
MeSH terms: Birth Weight
Study type: Interventional

Summary: 
      Prolacta Bioscience has developed the first purely human fortifier, Prolact-Plus, that can
      provide a source of many of the required nutrients for premature, newborn infants,
      particularly protein and calories. This product is made from donor human milk from which the
      skim (non-lipid portion) has been separated and then concentrated. A certain amount of the
      lipid content has been added back to achieve higher caloric content within a small delivery
      volume. The product is then pasteurized and filled in small quantities in order to allow for
      the addition of mother's own milk (or, possibly, milk from another donor). The goal of the
      preparation is to achieve an increase of approximately 4 cal/oz of mother's milk and to
      provide a protein level (when mixed with average pre-term milk) of about 3.5-3.8 g/100 Kcal
      of feed.

      The data on Prolact-Plus will be obtained prospectively from infants who will receive human
      milk fortified in this fashion. The data on standard,bovine (cow)-fortified milk will be
      obtained retrospectively from medical records at the participating institutions. While this
      design is not necessarily optimal in this setting, it is an efficient and quick approach to
      evaluating the acute clinical effect of Prolact-Plus. It is anticipated that further studies
      will be conducted that will examine longer-term accounts and possibly do this in a
      controlled, randomized environment.

      The goal of this study is to evaluate the short-term effect of Prolact-Plus fortified human
      milk when compared with bovine-based fortification of human milk on parameters such as growth
      and short-term development, infectious complications and incidence of feeding intolerance in
      a cohort design. Statistically, the study will attempt to evaluate a null hypothesis of
      equivalent results with respect to these parameters between the two types of fortifiers as
      compared with a two-sided alternative (difference between the groups).

      In addition, data will be collected on overall survival and length of stay in the NICU. These
      data will be collected for descriptive purposes, although an attempt will be made to compare
      the findings with those obtained from the bovine-based fortifier.
    

Detailed description: 
      This will be a cohort designed study in pre-term infants (<32 weeks of gestation) comparing
      bovine fortified (using any one of the commercially available fortifier products) human milk
      with Prolact-Plus (human) fortified human milk in which the former cohort will be obtained
      retrospectively and the latter obtained prospectively in each participating institution. The
      number of infants to be included in this study is a minimum of 50 in each group who complete
      the 30 days on study. (If a baby drops out of the study prior to 30 days of evaluation, then
      they would be replaced in order to achieve that number.) This sample size was not determined
      statistically, but rather is based solely on the desire to obtain a reasonable amount of data
      to evaluate the new human fortifier in this setting. However, from the perspective of a
      non-inferiority evaluation of an endpoint such as feeding intolerance, consider the
      following. Assuming a rate of 15% for this outcome for the retrospective cohort, then with 50
      subjects per cohort, the study would be able to demonstrate a lack of inferiority of the
      human-based fortifier with a delta of 20% using a power of slightly greater than 80% and a
      one-sided 2.5% significance level. (By a "delta of 20%" it is implied that a theoretical
      feeding intolerance rate for the Prolact-Plus of no worse than 35% would result in a
      conclusion of lack of inferiority with the given levels of significance and power.)
      Conversely, if the human-based fortifier is able to reduce the feeding intolerance rate from
      15% to about 1%, then with the sample sizes in this trial, this would be doable with 80%
      power and 5% significance (two-sided). (Thus, the trial, in theory, also could demonstrate a
      dramatic reduction in this rate.) The retrospective data will be obtained from available
      medical charts at the participating institution and the selected infants should reflect the
      most recently treated (within the 12 month period prior to the initiation of the prospective
      phase of this protocol) and the numbers should be similar in kind to the number treated
      prospectively in that institution.
    

Intervention name(s): Prolact-Plus Human Milk Fortifier
Intervention type(s): Procedure
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Human milk fortification; Premature neonate; Very low birth weight