NCT02552706

Brief Summary

The purpose of this study is to investigate the efficacy and its mechanisms of oral mixture probiotics in preventing necrotizing enterocolitis among the preterm very low birth weight infants.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
270

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2014

Typical duration for not_applicable

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2014

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

September 12, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 17, 2015

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2017

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2017

Completed
Last Updated

March 29, 2016

Status Verified

September 1, 2015

Enrollment Period

2.3 years

First QC Date

September 12, 2015

Last Update Submit

March 26, 2016

Conditions

Necrotizing EnterocolitisDeath

Keywords

probioticspreterm very low birth weight infantsnecrotizing enterocolitisgut microfloraTLRNF-KBinflammatory factors

Outcome Measures

Primary Outcomes (1)

  • the incidence of combined death and necrotizing enterocolitis

    at 36 weeks correct gestational age

Secondary Outcomes (1)

  • the incidence of sepsis,intraventricular hemorrhage(IVH)(grade 3-4),feeding intolerance(FI),bronchopulmonary dysplasia(BPD),parenteral nutrition associated liver disease(PNALD)and retinopathyof prematurity(ROP).

    participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Other Outcomes (1)

  • the influence of oral probiotics on gut microbiota and immunomodulatory

    at birth, 2 and 4 weeks of life, 36 week correct gestational age.

Study Arms (2)

probiotics group

EXPERIMENTAL

Administration of probiotics 500mg begins by mouth within 4 hours of life with 1-3 consecutive doses; the frequency depends on the feeding times. Study is continuous until preterm infants grow up to 36 weeks post menstrual age.

Dietary Supplement: probiotics

control group

PLACEBO COMPARATOR

control group received 1 mL of a 5% glucose solution. Administration of control group begins by mouth within 4 hours of life with 1-3 consecutive doses; the frequency depends on the feeding times. Study is also continuous until preterm infants grow up to 36 weeks post menstrual age.

Dietary Supplement: glucose solution

Interventions

probioticsDIETARY_SUPPLEMENT

Administration of mixture probiotics 500mg by mouth, one time or divided into 2-4 times depends on the feeding volume until to 36 weeks post menstrual age.

probiotics group
glucose solutionDIETARY_SUPPLEMENT

Administration of 1 mL of a 5% glucose solution by mouth, one time or divided into 2-4 times depends on the feeding volume until to 36 weeks post menstrual age.

control group

Eligibility Criteria

AgeUp to 3 Days
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Preterm infants ≦ 34 weeks gestational age and birth weight below 1500 gm and who survive to NICU are eligible for the trial.

You may not qualify if:

  • severe asphyxia (stage III),
  • fetal chromosomal anomalies,
  • cyanotic congenital heart disease,
  • congenital intestinal atresia, gastroschisis, omphalocele, active upper gastric intestinal bleeding,
  • lacking/refused of parental consent,
  • those who are fasted for \>3 weeks during the study period.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Longhua People's Hospital of Shenzhen

Shenzhen, Guangdong, 518100, China

ACTIVE NOT RECRUITING

Shenzhen Bao'an Maternal and Child Health Hospital

Shenzhen, Guangdong, 518100, China

RECRUITING

Shenzhen People's Hospital

Shenzhen, Guangdong, 518100, China

RECRUITING

Shenzhen Sixth People's Hospital

Shenzhen, Guangdong, 518100, China

ACTIVE NOT RECRUITING

Related Publications (19)

  • Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, Tsao LY, Chen CH, Su BH. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics. 2008 Oct;122(4):693-700. doi: 10.1542/peds.2007-3007.

    PMID: 18829790BACKGROUND

  • Genzel-Boroviczeny O, MacWilliams S, Von Poblotzki M, Zoppelli L. Mortality and major morbidity in premature infants less than 31 weeks gestational age in the decade after introduction of surfactant. Acta Obstet Gynecol Scand. 2006;85(1):68-73. doi: 10.1080/00016340500290947.

    PMID: 16521683RESULT

  • Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162-72. doi: 10.1016/S0140-6736(12)60820-4.

    PMID: 22682464RESULT

  • Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8. doi: 10.1136/adc.2006.099929. Epub 2006 Sep 19.

    PMID: 16984980RESULT

  • Huda S, Chaudhery S, Ibrahim H, Pramanik A. Neonatal necrotizing enterocolitis: Clinical challenges, pathophysiology and management. Pathophysiology. 2014 Feb;21(1):3-12. doi: 10.1016/j.pathophys.2013.11.009. Epub 2014 Feb 11.

    PMID: 24525171RESULT

  • Hall NJ, Eaton S, Pierro A. Royal Australasia of Surgeons Guest Lecture. Necrotizing enterocolitis: prevention, treatment, and outcome. J Pediatr Surg. 2013 Dec;48(12):2359-67. doi: 10.1016/j.jpedsurg.2013.08.006.

    PMID: 24314171RESULT

  • Quigley MA, Henderson G, Anthony MY, McGuire W. Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971. doi: 10.1002/14651858.CD002971.pub2.

    PMID: 17943776RESULT

  • Mshvildadze M, Neu J, Mai V. Intestinal microbiota development in the premature neonate: establishment of a lasting commensal relationship? Nutr Rev. 2008 Nov;66(11):658-63. doi: 10.1111/j.1753-4887.2008.00119.x.

    PMID: 19019028RESULT

  • Sharma R, Tepas JJ 3rd, Hudak ML, Mollitt DL, Wludyka PS, Teng RJ, Premachandra BR. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007 Mar;42(3):454-61. doi: 10.1016/j.jpedsurg.2006.10.038.

    PMID: 17336180RESULT

  • Nair V, Soraisham AS. Probiotics and prebiotics: role in prevention of nosocomial sepsis in preterm infants. Int J Pediatr. 2013;2013:874726. doi: 10.1155/2013/874726. Epub 2013 Jan 14.

    PMID: 23401695RESULT

  • Sarowska J, Choroszy-Krol I, Regulska-Ilow B, Frej-Madrzak M, Jama-Kmiecik A. The therapeutic effect of probiotic bacteria on gastrointestinal diseases. Adv Clin Exp Med. 2013 Sep-Oct;22(5):759-66.

    PMID: 24285463RESULT

  • Di Gioia D, Aloisio I, Mazzola G, Biavati B. Bifidobacteria: their impact on gut microbiota composition and their applications as probiotics in infants. Appl Microbiol Biotechnol. 2014 Jan;98(2):563-77. doi: 10.1007/s00253-013-5405-9. Epub 2013 Nov 28.

    PMID: 24287935RESULT

  • Liu Y, Fatheree NY, Mangalat N, Rhoads JM. Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-kappaB signaling in the intestine. Am J Physiol Gastrointest Liver Physiol. 2012 Mar 15;302(6):G608-17. doi: 10.1152/ajpgi.00266.2011. Epub 2011 Dec 29.

    PMID: 22207578RESULT

  • Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics. 2010 May;125(5):921-30. doi: 10.1542/peds.2009-1301. Epub 2010 Apr 19.

    PMID: 20403939RESULT

  • Lu P, Sodhi CP, Hackam DJ. Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis. Pathophysiology. 2014 Feb;21(1):81-93. doi: 10.1016/j.pathophys.2013.11.007. Epub 2013 Dec 22.

    PMID: 24365655RESULT

  • Hackam DJ, Afrazi A, Good M, Sodhi CP. Innate immune signaling in the pathogenesis of necrotizing enterocolitis. Clin Dev Immunol. 2013;2013:475415. doi: 10.1155/2013/475415. Epub 2013 May 23.

    PMID: 23762089RESULT

  • Ganguli K, Meng D, Rautava S, Lu L, Walker WA, Nanthakumar N. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol. 2013 Jan 15;304(2):G132-41. doi: 10.1152/ajpgi.00142.2012. Epub 2012 Nov 8.

    PMID: 23139215RESULT

  • Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2023 Jul 26;7(7):CD005496. doi: 10.1002/14651858.CD005496.pub6.

    PMID: 37493095DERIVED

  • Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2020 Oct 15;10(10):CD005496. doi: 10.1002/14651858.CD005496.pub5.

    PMID: 33058137DERIVED

MeSH Terms

Conditions

Enterocolitis, NecrotizingDeath

Interventions

Probiotics

Condition Hierarchy (Ancestors)

EnterocolitisGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary SupplementsFoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Yuefeng Li, M.D.

    Shenzhen Bao'an Maternal and Child Health Hospital

    PRINCIPAL INVESTIGATOR

  • HungChih Lin, M.D.

    China Medical University Hospital

    STUDY DIRECTOR

  • Benqing Wu, M.D.

    Shenzhen People's Hospital

    STUDY DIRECTOR

  • Xiaodong Li, M.D.

    Shenzhen Sixth People's Hospital

    STUDY DIRECTOR

  • Zhangxin Wang, M.D.

    Longhua Hospital Of Baoan District, Shenzhen

    STUDY DIRECTOR

Central Study Contacts

Yuefeng Li, M.D.

CONTACT

86+13751029103liyuefeng111@sina.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Ward chief of department of neonatology

Study Record Dates

First Submitted

September 12, 2015

First Posted

September 17, 2015

Study Start

September 1, 2014

Primary Completion

January 1, 2017

Study Completion

September 1, 2017

Last Updated

March 29, 2016

Record last verified: 2015-09

Locations

CN(4)