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Prophylactic Probiotics to Extremely Low Birth Weight Prematures (PROPEL)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01603368
First Posted: May 22, 2012
Last Update Posted: October 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
BioGaia AB
Ekhaga Foundation, Sweden
Medical Research Council of Southeast Sweden
University Hospital, Linkoeping
The Swedish Research Council
The Swedish Society of Medicine
Information provided by (Responsible Party):
Thomas Abrahamsson, Ostergotland County Council, Sweden
May 18, 2012
May 22, 2012
October 10, 2017
June 2012
December 2015   (Final data collection date for primary outcome measure)
Time to establish full enteral feeds [ Time Frame: Birth to gestational week 36+0 ]
The age of the infants in days when the infant receive 150 ml/kg/day via enteral feeding for the first time.
Same as current
Complete list of historical versions of study NCT01603368 on ClinicalTrials.gov Archive Site
  • Episodes with food intolerance [ Time Frame: Birth to gestational week 36 ]
    Episode with food intolerance. Retention volume> food volume given the last 2 hours (retention checked routinely every 4 hours) and/or clinical signs consistent with necrotizing enterocolitis (reduced general condition and inflated abdomen). The number of such events will also be indicated.
  • Stool frequency. [ Time Frame: Recorded over three days: gw35+0- 35+2 ]
  • Spitting/vomiting: the number recorded during the three days: v35 v35 +0- +2. [ Time Frame: gw 35+0-gw35+2. ]
    The number recorded during the three days
  • Crying [ Time Frame: gw35+0-35+2 ]
    defined as the cries for 3 hours or more during 3 days
  • Time until birth weight is regained. Specifies the number of full days the child has lived. [ Time Frame: Birth to gw 36+0 ]
    Specifies the number of full days the child has lived.
  • Weight, height and head circumference [ Time Frame: At 14 and 28 days of life and gw 36+0 ]
    In this analysis, the difference in standard deviation score (delta z-scores) for weight, height and head circumference at birth and 14 and 28 days and gestational week 36+0 will be calculated. At gestational week 36+0 also absolute values will be analyzed
  • Mortality [ Time Frame: Birth to gw 36+0 ]
  • Necrotizing enterocolitis [ Time Frame: Birth to gw 36+0 ]
    Bell´s criteria II-III
  • Sepsis [ Time Frame: Birth to gw 36+0 ]
    Divided into blood culture positive or clinical sepsis
  • Bronchopulmonary dysplasia [ Time Frame: Gw 36+0 ]
    Need of oxygen or CPAP/ventilator at gw 36+0
Same as current
Not Provided
Not Provided
 
Prophylactic Probiotics to Extremely Low Birth Weight Prematures
Prophylactic Probiotics to Extremely Low Birth Weight Prematures

Mortality and incidence of severe complications is still high among extremely premature infants. Common causes of severe complications in this population are poor nutrition, necrotizing enterocolitis, and severe infections. Feeding intolerance is also a common problem resulting in prolonged need for intravenous lines and poor nutrition.

The aim of the study is to evaluate whether supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 daily to premature infants with extremely low birth weight increases feeding tolerance to breast milk and thereby improves nutrition, increases growth and reduces serious complications and mortality in this population. Beyond this, possible mechanisms underlying these effects will be analyzed in stool, breast milk and blood samples.

RATIONALE Mortality and incidence of severe complications is still high among extremely premature infants. Common causes of severe complications in this population are poor nutrition, necrotizing enterocolitis (NEC), and severe infections. Feeding intolerance is also a common problem resulting in prolonged need for intravenous lines and poor nutrition. There is scientific evidence that dietary supplements with probiotics may have an effect on these manifestations.

Lactobacillus reuteri is a well studied probiotic bacterium that has been tested in several clinical studies in premature infants and older children, and the results of these studies and animal studies suggest that this bacterium may also have an effect on growth and mortality in extremely premature infants. Lactobacillus reuteri reduces colonization with pathogenic microbes, stimulates gastric and intestinal motility and shortens hospital stay in moderately premature infants. In animal models, L. reuteri also induces anti-inflammatory immune responses, reduces the symptoms of inflammatory bowel disease and the incidence of NEC. Administration of L. reuteri also improves the intestinal barrier both in human studies in children and in animal studies. Dietary supplements of L. reuteri to extremely premature infants may therefore improve feeding tolerance and nutrition and reduce the incidence of severe complications in this population.

HYPOTHESIS Premature infants with extremely low birth weight receiving daily supplements of Lactobacillus reuteri DSM 17938 will reach full enteral feeding faster compared with children receiving placebo.

STUDY DESIGN This study will be conducted as a prospective multi-center double blind placebo-controlled study in neonatal intensive care units in Sweden. In total 134 neonates with extremely low birth weight (<1000g) and gestational age <28+0 weeks will be randomized to receive either dietary supplements of Lactobacillus reuteri or placebo. Study product will be identical to the active and placebo group besides the addition of Lactobacillus reuteri (1.25 x 100 million bacteria=0.2 ml oil drops per day) in the active group. The supplementation will commence within 1-3 days after birth and will be given daily until gestational week 36+0. The infants will be followed until gestational week 36+0 and data on feeding tolerance, nutrition, growth, infections, NEC, bronchopulmonary dysplasia, death, and potential confounders will be entered in an individual study protocol. Stool, breast milk, and blood samples will be collected for analyses of possible underlying mechanisms.

A 2-year follow up including examination by pediatrician, growth parameters, questionnaire and psychology testing (Bayley´s test) will be performed.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Feeding; Difficult, Newborn
  • Growth Failure
  • Necrotizing Enterocolitis
  • Sepsis
  • Dietary Supplement: Lactobacillus reuteri
    Oil drops with Lactobacillus reuteri DSM 17938, 125 million bacteria=0.2 ml per day
  • Dietary Supplement: Placebo
    Oil drops without Lactobacillus reuteri
  • Active Comparator: Lactobacillus reuteri
    Lactobacillus reuteri DSM 17938, 125 million bacteria/day
    Intervention: Dietary Supplement: Lactobacillus reuteri
  • Placebo Comparator: Placebo
    The same oil drops as the active study product but without Lactobacillus reuteri
    Intervention: Dietary Supplement: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
134
December 2015
December 2015   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Birth weight < 1000 g
  • Gestational age: v23+0-V27 +6.
  • Age < 72 hours at inclusion.
  • Signed informed consent by parents.

Exclusion Criteria:

  • Fatal or complex congenital malformation at inclusion time.
  • Chromosomal defect at inclusion time.
  • No realistic hope of survival at inclusion time.
  • Gastrointestinal malformation at inclusion time.
  • Participation in another study which aims to influence nutrition, growth, feeding tolerance or necrotizing enterocolitis.
Sexes Eligible for Study: All
up to 3 Days   (Child)
Yes
Contact information is only displayed when the study is recruiting subjects
Sweden
 
 
NCT01603368
Dnr 2012/28-31
Yes
Not Provided
Not Provided
Thomas Abrahamsson, Ostergotland County Council, Sweden
Ostergotland County Council, Sweden
  • BioGaia AB
  • Ekhaga Foundation, Sweden
  • Medical Research Council of Southeast Sweden
  • University Hospital, Linkoeping
  • The Swedish Research Council
  • The Swedish Society of Medicine
Principal Investigator: Thomas Abrahamsson, MD, PhD Linköping University Hospital; County Council of Östergötland
Ostergotland County Council, Sweden
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP