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  • RAIN study: a protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection

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Paediatrics
Protocol
RAIN study: a protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection
  1. Fleur M Keij1,2,
  2. René F Kornelisse1,
  3. Nico G Hartwig2,
  4. Katya Mauff3,
  5. Marten J Poley4,5,
  6. Karel Allegaert1,6,
  7. Irwin K M Reiss1,
  8. Gerdien A Tramper-Stranders1,2
  1. 1 Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
  2. 2 Pediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
  3. 3 Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
  4. 4 Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
  5. 5 Medical Technology Assessment (iMTA), Erasmus University Rotterdam, Rotterdam, The Netherlands
  6. 6 Department of Development and Regeneration, KU Leuven, Leuven, Belgium
  1. Correspondence to Fleur M Keij; f.keij{at}erasmusmc.nl

Abstract

Introduction High morbidity and mortality rates of proven bacterial infection are the main reason for substantial use of intravenous antibiotics in neonates during the first week of life. In older children, intravenous-to-oral switch after 48 hours of intravenous therapy has been shown to have many advantages and is nowadays commonly practised. We, therefore, aim to evaluate the effectiveness, safety and cost-effectiveness of an early intravenous-to-oral switch in neonates with a probable bacterial infection.

Methods and analysis We present a protocol for a multicentre randomised controlled trial assessing the non-inferiority of an early intravenous-to-oral antibiotic switch compared with a full course of intravenous antibiotics in neonates (0–28 days of age) with a probable bacterial infection. Five hundred and fifty patients will be recruited in 17 hospitals in the Netherlands. After 48 hours of intravenous treatment, they will be assigned to either continue with intravenous therapy for another 5 days (control) or switch to amoxicillin/clavulanic acid suspension (intervention). Both groups will be treated for a total of 7 days. The primary outcome will be bacterial (re)infection within 28 days after treatment completion. Secondary outcomes are the pharmacokinetic profile of oral amoxicillin/clavulanic acid, the impact on quality of life, cost-effectiveness, impact on microbiome development and additional yield of molecular techniques in diagnosis of probable bacterial infection.

Ethics and dissemination This study has been approved by the Medical Ethics Committee of the Erasmus Medical Centre. Results will be presented in peer-reviewed journals and at international conferences.

Trial registration number NCT03247920

  • amoxicillin-clavulanic acid
  • intravenous-to-oral antibiotic switch therapy
  • cost-effectiveness
  • microbiome
  • neonatal infections

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjopen-2018-026688

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    Footnotes

    • Contributors GAT-S conceived the original idea for this trial. FMK, RFK, KM, MJP, NGH, KA and IKMR were involved in further conception and trial development. FMK wrote the first draft. FMK, GAT-S and RFK rewrote the article. GAT-S, RFK, KM, MJP, NGH, KA and IKMR critically revised the article for important intellectual content. All authors contributed to and approved the final version of the manuscript.

    • Funding This work is supported by The Netherlands Organisation for Health Research and Development (ZonMW) grant number 848015005 and the Innovatiefonds Zorgverzekeraars.

    • Competing interests None declared.

    • Ethics approval This study was approved by the Medical Ethics Committee of the Erasmus Medical Centre (NL51888.078.16, June 2017). The study will be conducted according to the principles of the Declaration of Helsinki (seventh revision, October 2013) and in accordance with the Medical Research Involving Human Subjects Act (WMO) and other guidelines, regulations and Acts such as Good Clinical Practice.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Patient consent for publication Not required.