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Abstract
Objective Definitive guidance regarding the duration of antibiotics for neonatal sepsis is lacking. We hypothesised that a 7-day antibiotic course is non-inferior to a 14-day course for treating culture-proven sepsis.
Design Randomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country.
Patients Neonates with a birth weight (BW) ≥1000 g and blood culture-proven sepsis were randomised on day 7 of sensitive antibiotic therapy provided sepsis had clinically remitted. Exclusions: Staphylococcus aureus or fungal sepsis, and infections requiring prolonged antibiotics. We planned to enrol 350 per group, assuming 10% rate of primary outcome, +7% non-inferiority margin, one-sided 5% alpha, 90% power, 10% loss to follow-up.
Intervention 7 days (no further treatment); comparison: 14 days (7 days postrandomisation).
Outcomes Primary: relapse (definite or probable) within day 21 postantibiotic completion. Secondary outcomes: composite of mortality or definite/probable/secondary sepsis and duration of hospitalisation. One interim analysis (per protocol (PP)) was planned.
Results 126 and 135 subjects were recruited in 7-day and 14-day groups, respectively, with mean (SD) birth weight (BW) 2250.9 (741.1) and 2187.8 (718.8) g. The trial was terminated early, based on interim PP analysis. 2/125 and 6/130 subjects had the primary outcome in 7-day and 14-day groups, respectively (risk difference (RD)=−3.0% (99.5% CI −9.2%, +3.1%), below non-inferiority margin). The composite secondary outcome also favoured the 7-day regimen (RD: −3.7% (99.5% CI −12.4% to +5.1%)). Duration of hospitalisation was shorter in 7-day group (median difference: −4 days (95% CI −5 to –3)).
Conclusions A 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis.
Trial registration number NCT03280147.
- Sepsis
- Neonatology
- Therapeutics
Data availability statement
Data are available upon reasonable request. Data collected for the study, including de-identified individual participant data and a data dictionary defining each field in the set will be made available to researchers who wish to conduct an individual patient data meta-analysis and who have a formal research proposal for the same approved by the necessary authorities. Additionally, the study protocol and the statistical analysis plan will be available. Data will be made available from after the last publication pertaining to the study until 5 years after that date. The data can be requested by sending an email to sourabhdutta1@gmail.com. A signed data access agreement will be required.
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Data availability statement
Data are available upon reasonable request. Data collected for the study, including de-identified individual participant data and a data dictionary defining each field in the set will be made available to researchers who wish to conduct an individual patient data meta-analysis and who have a formal research proposal for the same approved by the necessary authorities. Additionally, the study protocol and the statistical analysis plan will be available. Data will be made available from after the last publication pertaining to the study until 5 years after that date. The data can be requested by sending an email to sourabhdutta1@gmail.com. A signed data access agreement will be required.
Footnotes
X @DrSukshamj, @asmiisme
Contributors All the authors contributed substantially to the acquisition and analysis of data, reviewed the work for important intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work. The following are the additional specific contributions of individual authors: SD, SNa, MJ, MBS, MK, NS, GG and SNe contributed to the conception and design of the study, formulated the standard operating procedures, interpreted the data and contributed to drafting the manuscript. PK, AS, AK, ST, PB, PD and NB contributed to the design of the study, recruitment of subjects, training research staff and drafting the manuscript. PR, VSR, KS, DR, VV, BJ, MBS and SNN performed all the laboratory work for the study and interpreted the data in the study. SJ was the blinded adjudicator. MM, SD, SM, AS, NM, MD, AC, RAP, TS and LM contributed substantially to the acquisition and interpretation of the data, recruitment of subjects, formulation of standard operating procedures, and drafting the manuscript. AS and RR contributed to the interpretation of the data and the oversight and management of the trial.
Funding Indian Council of Medical Research (sanction order 5/7/329/2009-RHN dated 29/3/2017).
Disclaimer The funding agency did not play any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer-reviewed.
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