Trial Outcomes & Findings for A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome (NCT NCT02477423)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

27 participants

Primary outcome timeframe

2 weeks

Results posted on

2020-10-08

Participant Flow

Patients in the study were enrolled from The University of Chicago Comer Children's Hospital, a level IV NICU in Chicago, Illinois, as well as Northshore University HealthSystem Evanston Hospital, a level III NICU in Evanston, Illinois from 2015-2018.

Participant milestones

Participant milestones
Measure	Randomized & Blinded - Receiving Antibiotics 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Overall Study STARTED	12	15
Overall Study COMPLETED	11	11
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized & Blinded - Receiving Antibiotics n=12 Participants 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. Ampicillin: 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. Gentamicin: 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.	Randomized & Blinded - Receiving Placebo n=15 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.	Total n=27 Participants Total of all reporting groups
Age, Customized Gestational Age	32.6 weeks n=5 Participants	31.9 weeks n=7 Participants	32.3 weeks n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 weeks

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.

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=11 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=11 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Richness of the Preterm Infant Microbiome	12.8 16S rRNA gene amplicon sequence variants Standard Deviation 5.3	11 16S rRNA gene amplicon sequence variants Standard Deviation 6.9

PRIMARY outcome

Timeframe: 2 weeks

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.

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=11 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=11 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Shannon Diversity of the Preterm Infant Microbiome	5 Shannon diversity Standard Deviation 3.6	3.8 Shannon diversity Standard Deviation 3.3

SECONDARY outcome

Timeframe: 4-12 weeks

Premature infants who require \> 21% FiO2 for at least 28 days and/or at 36 weeks corrected gestation

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=12 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=15 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Chronic Lung Disease of Infancy (CLD)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4-12 weeks

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).

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=12 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=15 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Necrotizing Enterocolitis (NEC)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4-12 weeks

Cases of ROP as diagnosed by the pediatric ophthalmologist

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=12 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=15 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Retinopathy of Prematurity (ROP)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4-12 weeks

Cases of IVH present on any head ultrasound obtained during patient's hospitalization

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=12 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=15 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Intraventricular Hemorrhage (IVH)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 18 months

Outcome measures

Outcome measures
Measure	Randomized & Blinded - Receiving Antibiotics n=12 Participants 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. Ampicillin: 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. Gentamicins: 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.	Randomized & Blinded - Receiving Placebo n=15 Participants 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. Placebo: Normal saline will be given as placebo for those in the placebo comparator group.
Death	0 Participants	0 Participants

Adverse Events

Randomized & Blinded - Receiving Antibiotics

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Randomized & Blinded - Receiving Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Christina S. Kim

Neonatology, Department of Pediatrics, University of Chicago

Phone: 773-702-6210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place