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A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome

Primary Purpose

Premature Birth of Newborn, Enterocolitis, Necrotizing

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ampicillin
Gentamicins
Placebo
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Premature Birth of Newborn focused on measuring Microbiome, Antibiotics

Eligibility Criteria

undefined - 6 Hours (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria for antibiotic randomization:

  1. Infant must be born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks

    -AND-

  2. Infant must be born at investigator's home institution.

    -AND-

  3. Infant must be considered to have a low risk of infection by one of the following criteria:

    1. Delivered for maternal indications (Cesarean section or induction of labor for maternal health, including pre-eclampsia, placental abruption, history of intrauterine fetal demise (IUFD)/abruption, multiple gestation requiring preterm delivery, etc) -OR-
    2. Delivered due to preterm labor to a mother without the diagnosis of chorioamnionitis/maternal fever or prolonged rupture of membranes >18 hours

Exclusion Criteria for antibiotic randomization:

  1. Signs of clinical illness within the first 3 hours of life:

    1. 5-minute Apgar <5
    2. Requiring vasoactive drugs
    3. Seizures
    4. Significant respiratory distress requiring supplemental oxygen >40%
  2. Immature:Total (I:T) Ratio of >0.2 on initial complete blood count (CBC)
  3. Congenital anomalies, including renal anomalies requiring serum antibiotic level monitoring

ANY infant born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks who do not meet inclusion criteria, with parental consent, can participate in the stool analysis only arm of the study.

Sites / Locations

  • University of Chicago Medical Center - Comer Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Randomized & Blinded - Receiving Antibiotics

Randomized & Blinded - Receiving Placebo

Arm Description

The infants within this arm of the study meet the inclusion criteria as being low risk. They will be randomized to receive routine ampicillin and gentamicin for the initial 48 hours of their life as a routine rule-out sepsis. Stool samples will be collected throughout hospitalization and at 18 months of life.

The infants within this arm of the study meet the inclusion criteria as being low risk. They will be randomized to receive placebo (saline) in place of ampicillin and gentamicin for the initial 48 hours of their life as a routine rule-out sepsis. Stool samples will be collected throughout hospitalization and at 18 months of life.

Outcomes

Primary Outcome Measures

Richness of the Preterm Infant Microbiome
Number of 16S rRNA gene amplicon sequence variants (i.e., proxy for prokaryote species-like groupings) detected in each sample. A higher richness means that a higher number of species of archaea and bacteria was detected in a sample.
Shannon Diversity of the Preterm Infant Microbiome
Function of richness and evenness of 16S rRNA gene amplicon sequence variants (i.e., proxy for prokaryote species-like groupings) within each sample. A higher Shannon diversity means that a sample had a combination of a higher number of species of archaea and bacteria, and/or a more even relative abundance of those species within a sample.

Secondary Outcome Measures

Chronic Lung Disease of Infancy (CLD)
Premature infants who require > 21% FiO2 for at least 28 days and/or at 36 weeks corrected gestation
Necrotizing Enterocolitis (NEC)
Any patient showing signs/symptoms of this acute neonatal gastrointestinal disease, including abdominal distension, bloody stools, systemic illness, and radiographic changes (pneumatosis intestinalis, portal venous gas, free intraperitoneal gas).
Retinopathy of Prematurity (ROP)
Cases of ROP as diagnosed by the pediatric ophthalmologist
Intraventricular Hemorrhage (IVH)
Cases of IVH present on any head ultrasound obtained during patient's hospitalization
Death

Full Information

First Posted
June 16, 2015
Last Updated
September 14, 2020
Sponsor
University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT02477423
Brief Title
A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome
Official Title
A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether antibiotics given immediately after birth alter the development of the developing preterm infant's microbiome, which may further alter overall clinical outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Premature Birth of Newborn, Enterocolitis, Necrotizing
Keywords
Microbiome, Antibiotics

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Randomized & Blinded - Receiving Antibiotics
Arm Type
Active Comparator
Arm Description
The infants within this arm of the study meet the inclusion criteria as being low risk. They will be randomized to receive routine ampicillin and gentamicin for the initial 48 hours of their life as a routine rule-out sepsis. Stool samples will be collected throughout hospitalization and at 18 months of life.
Arm Title
Randomized & Blinded - Receiving Placebo
Arm Type
Placebo Comparator
Arm Description
The infants within this arm of the study meet the inclusion criteria as being low risk. They will be randomized to receive placebo (saline) in place of ampicillin and gentamicin for the initial 48 hours of their life as a routine rule-out sepsis. Stool samples will be collected throughout hospitalization and at 18 months of life.
Intervention Type
Drug
Intervention Name(s)
Ampicillin
Intervention Description
Ampicillin will be given as routine antibiotic coverage for those in the active arm, as the standard initial antibiotic used within the neonatal unit. It may also be used for patients who are not eligible for randomization.
Intervention Type
Drug
Intervention Name(s)
Gentamicins
Intervention Description
Gentamicin will be given as routine antibiotic coverage for those in the active arm, as the standard initial antibiotic used within the neonatal unit. It may also be used for patients who are not eligible for randomization.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline will be given as placebo for those in the placebo comparator group.
Primary Outcome Measure Information:
Title
Richness of the Preterm Infant Microbiome
Description
Number of 16S rRNA gene amplicon sequence variants (i.e., proxy for prokaryote species-like groupings) detected in each sample. A higher richness means that a higher number of species of archaea and bacteria was detected in a sample.
Time Frame
2 weeks
Title
Shannon Diversity of the Preterm Infant Microbiome
Description
Function of richness and evenness of 16S rRNA gene amplicon sequence variants (i.e., proxy for prokaryote species-like groupings) within each sample. A higher Shannon diversity means that a sample had a combination of a higher number of species of archaea and bacteria, and/or a more even relative abundance of those species within a sample.
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Chronic Lung Disease of Infancy (CLD)
Description
Premature infants who require > 21% FiO2 for at least 28 days and/or at 36 weeks corrected gestation
Time Frame
4-12 weeks
Title
Necrotizing Enterocolitis (NEC)
Description
Any patient showing signs/symptoms of this acute neonatal gastrointestinal disease, including abdominal distension, bloody stools, systemic illness, and radiographic changes (pneumatosis intestinalis, portal venous gas, free intraperitoneal gas).
Time Frame
4-12 weeks
Title
Retinopathy of Prematurity (ROP)
Description
Cases of ROP as diagnosed by the pediatric ophthalmologist
Time Frame
4-12 weeks
Title
Intraventricular Hemorrhage (IVH)
Description
Cases of IVH present on any head ultrasound obtained during patient's hospitalization
Time Frame
4-12 weeks
Title
Death
Time Frame
18 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
6 Hours
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for antibiotic randomization: Infant must be born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks -AND- Infant must be born at investigator's home institution. -AND- Infant must be considered to have a low risk of infection by one of the following criteria: Delivered for maternal indications (Cesarean section or induction of labor for maternal health, including pre-eclampsia, placental abruption, history of intrauterine fetal demise (IUFD)/abruption, multiple gestation requiring preterm delivery, etc) -OR- Delivered due to preterm labor to a mother without the diagnosis of chorioamnionitis/maternal fever or prolonged rupture of membranes >18 hours Exclusion Criteria for antibiotic randomization: Signs of clinical illness within the first 3 hours of life: 5-minute Apgar <5 Requiring vasoactive drugs Seizures Significant respiratory distress requiring supplemental oxygen >40% Immature:Total (I:T) Ratio of >0.2 on initial complete blood count (CBC) Congenital anomalies, including renal anomalies requiring serum antibiotic level monitoring ANY infant born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks who do not meet inclusion criteria, with parental consent, can participate in the stool analysis only arm of the study.
Facility Information:
Facility Name
University of Chicago Medical Center - Comer Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome

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