7 Days Versus 14 Days of Antibiotics for Neonatal Sepsis

October 30, 2023 updated by: Sourabh Dutta, Indian Council of Medical Research

Comparison of the Efficacy of a 7-day Versus 14-day Course of Intravenous Antibiotics in the Treatment of Uncomplicated Neonatal Bacterial Sepsis: a Randomized Controlled Non-inferiority Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The optimum duration of intravenous antibiotic therapy for uncomplicated neonatal bacterial septicemia is not known. Pediatricians administer anywhere between 7 to 14 days of antibiotics, but these practices are not evidence based. C reactive protein (CRP) guided antibiotic duration is based on limited data and serial quantitative CRP is both cumbersome and not universally available. If it could be demonstrated that a 7-day course of antibiotics is not inferior to a 14-day course of antibiotics in terms of relapse rates of infection, then a 7 day course of antibiotics could be uniformly adopted, resulting in economic savings, shorter duration of hospitalization, less chances of hospital acquired infections, less chances of antibiotic induced adverse events and less antibiotic resistance. To test this hypothesis, a randomized, active-controlled, multi-centric, non-inferiority trial to compare the efficacy of a 7-day course of intravenous antibiotics with a 14-day course has been planned. Subjects weighing more than 1000 g at birth with suspected sepsis will be enrolled and observed for a 7-day period to see if they meet eligibility criteria for randomization. Subjects will be randomized on the 7th day of antibiotics, if the initial blood culture grows a non-Staphylococcus aureus bacterial organism, if they have no meningitis, osteomyelitis, septic arthritis or deep seated abscess and if the sepsis goes into clinical remission by the 5th day and remains in remission up to the 7th day of sensitive antibiotics. Subjects in the 14-day group will receive 7 more days of antibiotics after randomization, whereas those in the 7-day group will receive no further antibiotics after randomization. Subjects will be followed up for a 35-day period after randomization. The key outcome will be treatment failure as measured by "definite or probable relapse" within a 21-day period after completion of antibiotic therapy. Secondary outcomes will include definite relapse within 21 and 28 days after antibiotic completion and within 28 and 35 days after randomization; and probable relapse at similar time points. Other secondary outcomes will include secondary infections and adverse events. A total sample size of 700 (350 in each arm) will be required to detect a non-inferiority margin of 7%, assumed event rate of 10%, with 90% power, one-sided alpha error of 5% and loss to follow-up of approximately 10%. Data safety monitoring board will monitor serious adverse events in the trial and will perform at 1/3rd and 2/3rd of expected recruitment. At the time of interim analysis, the DSMB will revisit the sample size of the study. O'Brien Fleming's stopping criteria will be used for the primary outcome while Pocock's stopping rule will be used for the serious adverse events.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
261

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • India
      • Chandigarh, India, 160023
        • Postgraduate Institute of Medical Education and Research
      • New Delhi, India, 110001
        • Kalawati Saran Childrens Hospital and Lady Hardinge Medical College
      • New Delhi, India, 110031
        • Chacha Nehru Bal Chikitsalaya
    • Haryana
      • Rohtak, Haryana, India, 124001
        • Pandit BD Sharma Postgraduate Institute of Medical Sciences
    • Karnataka
      • Bangalore, Karnataka, India, 560029
        • Indira Gandhi Institute of child health
    • Tamil NADU
      • Chennai, Tamil NADU, India, 600008
        • Madras Medical College (for Institute of Obstetrics and Gynaecology)
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India, 226003
        • King Georges Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 hour to 4 weeks (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Inclusion criteria for the initial observation part of study preceding randomization

  1. Neonates aged 0-28 days, either inborn or outborn, who are currently admitted in the Neonatal Unit of the centre.
  2. Whose birth weight is greater than or equal to1000 grams (it should be reliably ascertained from records of a hospital)
  3. Whose residence is within approximately 15 kms from the center, so that the infant can be brought back to the center for follow-up
  4. 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

Inclusion criteria for Randomization applicable after 7 days of therapy of above patients with sensitive antibiotics:

  1. Positive blood culture other than Staphylococcus aureus
  2. No signs and symptoms of sepsis from end of day 5 through end of day 7 of starting sensitive antibiotics

Exclusion Criteria:

Exclusion criteria for the initial observation part of study preceding randomization:

  1. 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)]
  2. Septic arthritis, osteomyelitis or deep-seated abscess as clinically judged by the treating team
  3. Life threatening congenital malformations as judged by the principal investigator of the centre

Exclusion criteria for randomization applicable after 7 days of therapy of above patients with sensitive antibiotics:

  1. Sterile blood culture
  2. Suspected contaminants in blood culture.
  3. Growth of Staphylococcus aureus in blood culture
  4. Growth of fungal organism in blood culture
  5. Diagnosis of meningitis, septic arthritis, osteomyelitis, abscess
  6. Has not gone into remission on day 5 or have recurrence of symptoms from day 5 through day 7
  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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 7-day course of antibiotics
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
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.
Active Comparator: 14-day course of antibiotics
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Definite or probable relapse within 21 days post-antibiotic completion as per protocol
Time Frame: From 0-21 days after the end of the planned antibiotic therapy
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
Time Frame: From 0-21 days after the end of the planned antibiotic therapy
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Definite relapse within 21 days post-antibiotic completion, as per protocol
Time Frame: From 0-21 days after the end of the planned antibiotic therapy
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
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
Time Frame: From 0-21 days after the end of the planned antibiotic therapy
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
From 0-21 days after the end of the planned antibiotic therapy
Definite relapse within 28 days post-antibiotic completion, as per protocol
Time Frame: From 0-28 days after the end of the planned antibiotic therapy
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
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
Time Frame: From 0-28 days after the end of the planned antibiotic therapy
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
From 0-28 days after the end of the planned antibiotic therapy
Definite relapse within 28 days post-randomization, as per protocol
Time Frame: From 0-28 days after randomization
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
From 0-28 days after randomization
Definite relapse within 28 days post-randomization, as per Intention-to-treat
Time Frame: From 0-28 days after randomization
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
From 0-28 days after randomization
Definite relapse within 35 days post-randomization, as per protocol
Time Frame: From 0-35 days after randomization
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
From 0-35 days after randomization
Definite relapse within 35 days post-randomization, as per intention to treat
Time Frame: From 0-35 days after randomization
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
From 0-35 days after randomization
Probable relapse within 21 days post-antibiotic completion, as per protocol
Time Frame: From 0-21 days after the end of the planned antibiotic therapy
Among participants who adhered to study protocol 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
Probable relapse within 21 days post-antibiotic completion, as per intention-to-treat
Time Frame: From 0-21 days after the end of the planned antibiotic therapy
Among all randomized patients 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
Probable relapse within 28 days post-antibiotic completion, as per protocol
Time Frame: From 0-28 days after the end of the planned antibiotic therapy
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
From 0-28 days after the end of the planned antibiotic therapy
Probable relapse within 28 days post-antibiotic completion, as per intention-to-treat
Time Frame: From 0-28 days after the end of the planned antibiotic therapy
Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
From 0-28 days after the end of the planned antibiotic therapy
Probable relapse within 28 days post-randomization, as per protocol
Time Frame: From 0-28 days after randomization
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
From 0-28 days after randomization
Probable relapse within 28 days post-randomization, as per intention-to-treat
Time Frame: From 0-28 days after randomization
Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
From 0-28 days after randomization
Probable relapse within 35 days post-randomization, as per protocol
Time Frame: From 0-35 days after randomization
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
From 0-35 days after randomization
Probable relapse within 35 days post-randomization, as per intention-to-treat
Time Frame: From 0-35 days after randomization
Among all randomised patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
From 0-35 days after randomization
Definite relapse or probable relapse within 28 days post-randomization, as per protocol
Time Frame: From 0-28 days after randomization
Among participants who adhered to study protocol Definite relapse defined as: 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 0-28 days after randomization
Definite relapse or probable relapse within 28 days post-randomization, as per Intention-to-treat
Time Frame: From 0-28 days after randomization
Among all randomized patients Definite relapse defined as: 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 0-28 days after randomization
Definite relapse or probable relapse within 35 days post-randomization, as per protocol
Time Frame: From 0-35 days after randomization
Among participants who adhered to study protocol Definite relapse defined as: 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 0-35 days after randomization
Definite relapse or probable relapse within 35 days post-randomization, as per intention-to-treat
Time Frame: From 0-35 days after randomization
Among all randomised patients Definite relapse defined as: 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 0-35 days after randomization
Secondary sepsis
Time Frame: From 0-35 days after randomization
Sepsis due to bacterial organisms other than the original etiologic bacteria or with a different antibiogram or with a fungal organism
From 0-35 days after randomization
Adverse events
Time Frame: From 0-35 days after randomization
Adverse events as per a list of adverse events, graded as per severity, and defined a priori
From 0-35 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indian Council of Medical Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
King George's Medical University
Lady Hardinge Medical College
Postgraduate Institute of Medical Education and Research, Chandigarh
St Johns Medical College Hospital, Bangalore, India
Chacha Nehru Bal Chikitsalaya, New Delhi
Indira Gandhi Institute of Child Health, Bangalore
Institute of Obstetrics and Gynecology, Chennai
Pandit Bhagwat Dayal Sharma, PGIMS, Rohtak

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sourabh Dutta, Postgraduate Institute of Medical Education and Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 9, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 12, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5/7/329/2009-RHN

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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