7 Days Versus 14 Days of Antibiotics for Neonatal Sepsis

NCT03280147 | Completed Phase 3 DMC

• 1 other identifier: 5/7/329/2009-RHN
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 7

Brief Summary

The optimum duration of intravenous antibiotic therapy for culture-proven neonatal bacterial sepsis is not known. Current practices, ranging from 7 days to 14 days of antibiotics, are not evidence-based. This is a randomized, active -controlled, multi-centric, non-inferiority trial to compare the efficacy of a 7-day course of intravenous antibiotics versus a 14-day course among neonates weighing \> 1000 g at birth with culture-proven bacterial sepsis that is uncomplicated by meningitis, bone or joint infections deep-seated abscesses. The primary outcome measure is a definite or probable relapse within 21 days after stoppage of antibiotics.

Conditions

Infant, Newborn; Neonatal SEPSIS; Anti-bacterial Agents; Recurrence

Keywords

Neonate; Sepsis; Antibiotics; Duration

Outcome Measures

Primary Outcomes (2)

• Definite or probable relapse within 21 days post-antibiotic completion as per protocol

  Among participants who adhered to study protocol- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  From 0-21 days after the end of the planned antibiotic therapy

• Definite or probable relapse within 21 days post-antibiotic completion as per intention to treat

  Among all randomized patients- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.

  From 0-21 days after the end of the planned antibiotic therapy

Secondary Outcomes (22)

• Definite relapse within 21 days post-antibiotic completion, as per protocol

  From 0-21 days after the end of the planned antibiotic therapy

• Definite relapse within 21 days post-antibiotic completion, as per intention-to-treat

  From 0-21 days after the end of the planned antibiotic therapy

• Definite relapse within 28 days post-antibiotic completion, as per protocol

  From 0-28 days after the end of the planned antibiotic therapy

• Definite relapse within 28 days post-antibiotic completion, as per intention-to-treat

  From 0-28 days after the end of the planned antibiotic therapy

• Definite relapse within 28 days post-randomization, as per protocol

  From 0-28 days after randomization

Study Arms (2)

7-day course of antibiotics

EXPERIMENTAL

Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 7-day group will not receive any further antibiotics.

Drug: 7-day course of antibiotics

14-day course of antibiotics

ACTIVE COMPARATOR

Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 14-day group will receive 7 more days of the same antibiotics, to make it a total of 14 days.

Drug: 14-day course of antibiotics

Interventions

7-day course of antibiotics DRUG

Subjects in the "7-day course of antibiotics" arm of the study will receive no further antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.

7-day course of antibiotics

14-day course of antibiotics DRUG

Subjects in the "14-day course of antibiotics" arm of the study will receive 7 more days of antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.

14-day course of antibiotics

Eligibility Criteria

• Age: 1 Hour - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates aged 0-28 days, either inborn or outborn, who are currently admitted in the Neonatal Unit of the centre.
• Whose birth weight is greater than or equal to1000 grams (it should be reliably ascertained from records of a hospital)
• Whose residence is within approximately 15 kms from the center, so that the infant can be brought back to the center for follow-up
• Who have suspected septicemia for which a conventional or BACTEC/BACTALERT blood culture is sent and for which the treating physician decides to start antibiotics
• Positive blood culture other than Staphylococcus aureus
• No signs and symptoms of sepsis from end of day 5 through end of day 7 of starting sensitive antibiotics

You may not qualify if:

• Central Nervous System infection (Central Nervous System infection (meningitis will be defined as CSF Cells \>25 per uL with polys \>60% OR \[(CSF glucose \<20 mg/dL OR CSF:blood\* glu ratio \<0.6) AND (CSF protein \>150 mg/dL in term OR \>180 mg/dL in preterm)\]
• Septic arthritis, osteomyelitis or deep-seated abscess as clinically judged by the treating team
• Life threatening congenital malformations as judged by the principal investigator of the centre
• Sterile blood culture
• Suspected contaminants in blood culture.
• Growth of Staphylococcus aureus in blood culture
• Growth of fungal organism in blood culture
• Diagnosis of meningitis, septic arthritis, osteomyelitis, abscess
• Has not gone into remission on day 5 or have recurrence of symptoms from day 5 through day 7
• If the empiric antibiotic is resistant but neonate has shown improvement of signs and symptoms of sepsis and there is ambiguity regarding in vivo sensitivity of antibiotic use

Sponsors & Collaborators

• Indian Council of Medical Research: lead
• Post Graduate Institute of Medical Education and Research, Chandigarh: collaborator
• Chacha Nehru Bal Chikitsalaya, New Delhi: collaborator
• Lady Hardinge Medical College: collaborator
• Indira Gandhi Institute of Child Health, Bangalore: collaborator
• Institute of Obstetrics and Gynecology, Chennai: collaborator
• King George's Medical University: collaborator
• Pandit Bhagwat Dayal Sharma, PGIMS, Rohtak: collaborator
• St Johns Medical College Hospital, Bangalore, India: collaborator

Study Sites (7)

Pandit BD Sharma Postgraduate Institute of Medical Sciences

Rohtak, Haryana, 124001, India

Location

Indira Gandhi Institute of Child Health

Bangalore, Karnataka, 560029, India

Location

Madras Medical College (for Institute of Obstetrics and Gynaecology)

Chennai, Tamil Nadu, 600008, India

Location

King Georges Medical University

Lucknow, Uttar Pradesh, 226003, India

Location

Postgraduate Institute of Medical Education and Research

Chandigarh, 160023, India

Location

Kalawati Saran Childrens Hospital and Lady Hardinge Medical College

New Delhi, 110001, India

Location

Chacha Nehru Bal Chikitsalaya

New Delhi, 110031, India

Location

Related Publications (1)

• Dutta S, Nangia S, Jajoo M, Sundaram M, Kumar M, Shivanna N, Gathwala G, Nesargi S, Jain S, Kumar P, Saili A, Karthik A, Tripathi S, Bandiya P, Dalal P, Ray P, Randhawa VS, Saigal K, Radhakrishnan D, Venkatesh V, Jagannatha B, Sharma M, Nagaraj S, Malik M, Dogra S, Mittal S, Saini A, Makkar N, Dhir M, Chandramohan A, Pragati RA, Srivastava T, Mukundan L, Benakappa N, Shukla A, Rasaily R. Seven-day versus 14-day antibiotic course for culture-proven neonatal sepsis: a multicentre randomised non-inferiority trial in a low and middle-income country. Arch Dis Child Fetal Neonatal Ed. 2025 Oct 17;110(6):586-594. doi: 10.1136/archdischild-2024-328232.

  PMID: 40280737 DERIVED

MeSH Terms

Conditions

Neonatal Sepsis; Recurrence; Sepsis

Condition Hierarchy (Ancestors)

Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Sourabh Dutta

  Post Graduate Institute of Medical Education and Research, Chandigarh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessor will be provided objective clinical information related to episodes of all illnesses during follow-up with all patient identifiers removed and the record identified only by a unique code number. All imaging films and investigation reports provided to the outcome assessor will be similarly bereft of patient identifiers and coded by a unique code number. The outcome assessor will not be involved in the rest of the study. The outcome assessor will adjudicate whether the given episode of illness is a relapse.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, outcome-assessor blinded, active-controlled, multi-centric, non-inferiority trial

Study Record Dates

• First Submitted: September 9, 2017
• First Posted: September 12, 2017
• Study Start: January 1, 2019
• Primary Completion: January 30, 2023
• Study Completion: January 31, 2023
• Last Updated: November 2, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

IN (7)