The Efficacy and Mechanisms of Oral Probiotics in Preventing Necrotizing Enterocolitis

NCT ID: NCT02552706

Last Updated: 2016-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-30

Study Completion Date

2017-09-30

Brief Summary

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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.

Detailed Description

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Necrotizing enterocolitis (NEC) remains the most catastrophic gastrointestinal emergencies in preterm very low birth weight (VLBW) infants.Although study showed it is a multifactorial disease, its pathogenesis is still not yet unclear currently. Prematurity and formula feeding is considered as the main risk factors.Gut microbiota disturbance and immature immune system is associated with NEC. A lot of studies had showed that oral probiotics can alter gut microbiota flora colonization and reduce the incidence of NEC,but the exact mechanism remains unclear.The aim of this study is to elucidate the clinical efficacy and possible molecular mechanism of oral mixture probiotics in preventing NEC among preterm VLBW infants.

Patient Registry procedures: First,randomized numbers was generated by the computer and sent to the principal investigator(PI) at each center when an infant was eligible for enrollment.Second, patient will be assigned randomly to experimental group or control group by PI.Finally,the PI at each center will be responsible for the accuracy,completeness or representativeness of medical records, registry forms,data collection.

Sample size determination: The incidence of death and NEC was around 20% recently.To reduce the incidence of NEC and death to 10% at discharge would require a 50% improvement.At 80% power at P = 0.05 (two-sided),the loss rate of 0.2, this would require 135 subjects per arm.

Statistical analysis:The two groups were compared by a Χ2-test for categorical variables,Mann-Whitney U Test were used when reporting medians.A P value of \<0.05 was considered statistically significant.

Conditions

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Necrotizing Enterocolitis Death

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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probiotics group

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.

Group Type EXPERIMENTAL

probiotics

Intervention Type DIETARY_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.

control group

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.

Group Type PLACEBO_COMPARATOR

glucose solution

Intervention Type DIETARY_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.

Interventions

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probiotics

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.

Intervention Type DIETARY_SUPPLEMENT

glucose solution

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.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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.
Maximum Eligible Age

3 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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China Medical University Hospital

OTHER

Sponsor Role collaborator

Shenzhen People's Hospital

OTHER

Sponsor Role collaborator

Shenzhen Sixth People's Hospital

OTHER

Sponsor Role collaborator

Longhua Hospital Of Baoan District, Shenzhen

OTHER

Sponsor Role collaborator

Shenzhen Bao'an Maternal and Child Health Hospital

OTHER

Sponsor Role lead

Responsible Party

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liyuefeng

Ward chief of department of neonatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yuefeng Li, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Bao'an Maternal and Child Health Hospital

HungChih Lin, M.D.

Role: STUDY_DIRECTOR

China Medical University Hospital

Benqing Wu, M.D.

Role: STUDY_DIRECTOR

Shenzhen People's Hospital

Xiaodong Li, M.D.

Role: STUDY_DIRECTOR

Shenzhen Sixth People's Hospital

Zhangxin Wang, M.D.

Role: STUDY_DIRECTOR

Longhua Hospital Of Baoan District, Shenzhen

Locations

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Longhua People's Hospital of Shenzhen

Shenzhen, Guangdong, China

Site Status ACTIVE_NOT_RECRUITING

Shenzhen Bao'an Maternal and Child Health Hospital

Shenzhen, Guangdong, China

Site Status RECRUITING

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Site Status RECRUITING

Shenzhen Sixth People's Hospital

Shenzhen, Guangdong, China

Site Status ACTIVE_NOT_RECRUITING

Countries

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China

Central Contacts

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Yuefeng Li, M.D.

Role: CONTACT

86+13751029103

Facility Contacts

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Yuefeng Li, M.D.

Role: primary

+86-13751029103

Benqing Wu, M.D.

Role: primary

+86-13902436593

References

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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.

Reference Type BACKGROUND
PMID: 18829790 (View on PubMed)

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.

Reference Type RESULT
PMID: 16521683 (View on PubMed)

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.

Reference Type RESULT
PMID: 22682464 (View on PubMed)

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.

Reference Type RESULT
PMID: 16984980 (View on PubMed)

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.

Reference Type RESULT
PMID: 24525171 (View on PubMed)

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.

Reference Type RESULT
PMID: 24314171 (View on PubMed)

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.

Reference Type RESULT
PMID: 17943776 (View on PubMed)

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.

Reference Type RESULT
PMID: 19019028 (View on PubMed)

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.

Reference Type RESULT
PMID: 17336180 (View on PubMed)

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.

Reference Type RESULT
PMID: 23401695 (View on PubMed)

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.

Reference Type RESULT
PMID: 24285463 (View on PubMed)

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.

Reference Type RESULT
PMID: 24287935 (View on PubMed)

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.

Reference Type RESULT
PMID: 22207578 (View on PubMed)

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.

Reference Type RESULT
PMID: 20403939 (View on PubMed)

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.

Reference Type RESULT
PMID: 24365655 (View on PubMed)

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.

Reference Type RESULT
PMID: 23762089 (View on PubMed)

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.

Reference Type RESULT
PMID: 23139215 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37493095 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33058137 (View on PubMed)

Other Identifiers

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LL2014006

Identifier Type: -

Identifier Source: org_study_id

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