PREMAPROB. Probiotics to Prevent Necrotizing Enterocolitis

Effects of Probiotic Supplementation During the Neonatal Period on the Preterm Infant

The main objective of this study is to assess the impact of two different doses of a mixture of probiotics from two strains isolated in human milk on the incidence of severe necrotizing enterocolitis (NEC) and death among preterm infants of gestational age less than or equal to 32 weeks of gestation and weighing between 750 and 1500 g.

Study Overview

• Status: Completed
• Conditions: Necrotizing Enterocolitis; Premature Infants
• Intervention / Treatment: Dietary supplement: High dose group; Dietary supplement: Low dose group

• Study Type: Interventional
• Enrollment (Actual): 583
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Granada, Spain, 18012
    • Hospital Virgen de las Nieves

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Preterm infants of gestational age less than 33 weeks of gestation with birth weight below 1500 g, admitted to the Neonatology Unit.
• Premature newborns who meet the above criteria and receive enteral feeding (mother breast milk, donors milk and/or premature formula) from the amount of 5 ml/kg/day.

Exclusion Criteria:

• Any clinical circumstance that prevents the initiation of enteral nutrition in the first 72 hours of life.
• Chromosomopathies and complex fetal malformations, incompatible with enteral nutrition in the first 72 hours of life.
• Non-acceptance of informed consent to participate in the study by the parents or legal guardians of the newborn.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose of probiotic mixture; A daily high dose of a mixture of probiotics (Lactobacillus Fermentum CECT 5716 and Bifidobacterium breve CECT 7263), was given orally starting in the first 72 hours of life, until 36+6 weeks of postmenstrual age or discharge The total dose was 1x109 CFU of each of the strains	Dietary supplement: High dose group; A daily high dose of a mixture of probiotics (Lactobacillus Fermentum CECT 5716 and Bifidobacterium breve CECT 7263), was given orally starting in the first 72 hours of life, until 36+6 weeks of postmenstrual age or discharge The total dose was 1x109 CFU of each of the strains
Experimental: Low dose of probiotic mixture; A daily low dose of a mixture of probiotics (Lactobacillus Fermentum CECT 5716 and Bifidobacterium breve CECT 7263), was given orally starting in the first 72 hours of life, until 36+6 weeks of postmenstrual age or discharge The total dose was 1x106 CFU of each of the strains	Dietary supplement: Low dose group; A daily low dose of a mixture of probiotics (Lactobacillus Fermentum CECT 5716 and Bifidobacterium breve CECT 7263), was given orally starting in the first 72 hours of life, until 36+6 weeks of postmenstrual age or discharge The total dose was 1x106 CFU of each of the strains

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of necrotizing enterocolitis and all-cause mortality	The primary objective of the study was to determine the incidence of necrotizing enterocolitis (modified Bell classification stages II and III) and all-cause mortality during hospital stay in both intervention groups.	From birth until three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal colonization by administered strains		From birth until three months
Incidence of Late Onset Sepsis	Incidence of Late Onset Sepsis. In accordance with the criteria used by the Castrillo Group for neonatal infections in Spain (compatible clinical symptoms, elevation of water-phase reactants and positive blood culture)	From birth until three months
Time to complete enteral nutrition	Time to reach complete enteral nutrition 140 ml/kg/day	From birth until three months
Days of Central Vascular Catheter		From birth until three months
Length of hospital stay	Days of hospital stay	From birth until three months
Weight change		From birth until three months
Incidence of Bronchopulmonary Dysplasia		From birth until three months
Incidence of patent ductus arteriosus		From birth until three months

Collaborators and Investigators

• Sponsor: José Antonio Hurtado Suazo
• Collaborators: Hospital del SAS de Jerez; Hospital Universitario Virgen Macarena; Hospital General Universitario Santa Lucia; Hospitales Universitarios Virgen del Rocío; Hospital Regional de Malaga; Hospital Costa del Sol; Hospital Universitario Puerta del Mar; University Hospital Virgen de las Nieves; Hospital Universitario Torrecárdenas; Complejo Hospitalario de Especialidades Juan Ramón Jimenez; Hospital Universitario de Valme; Hospital of Jaen

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2015
• Primary Completion (Actual): January 15, 2015
• Study Completion (Actual): March 20, 2020

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: PN01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No