Reduction of Intravenous Antibiotics In Neonates
RAIN
Intravenous to Oral Antibiotic Switch Therapy for Probable Neonatal Bacterial Infections: Clinical Efficacy, Safety and Cost-effectiveness
1 other identifier
interventional
510
1 country
18
Brief Summary
Randomized controlled open-label non-inferiority trial comparing complete intravenous antibiotic treatment with a short iv. course followed by oral antibiotics in neonates (0-28 days) with probable bacterial infection. Primary outcome: \- Bacterial re-infection within 28 days after finishing of antibacterial therapy. Secondary outcome(s):
- Pharmacokinetic profile of oral amoxicillin/clavulanic acid
- Quality of life
- Cost-effectiveness
- Alterations in gut microbiome
- Use of molecular techniques for better detection of bacterial pathogens
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Nov 2017
Longer than P75 for phase_4
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 3, 2017
CompletedFirst Posted
Study publicly available on registry
August 14, 2017
CompletedStudy Start
First participant enrolled
November 4, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 15, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
July 15, 2021
CompletedAugust 24, 2021
August 1, 2021
3.6 years
July 3, 2017
August 23, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Bacterial re-infection within 28 days after cessation of antibiotic treatment (within 35 days after initial presentation)
0-35 days
Secondary Outcomes (6)
Duration of hospitalization
0-35 days after birth
Percentage of re-admission
0-35 days after birth
Total costs and cost-effectiveness
0-35 days after birth
Difference in Quality of Life between oral and intravenous antibiotic treatment
0-35 days after birth
Time above MIC (T>MIC) of oral amoxicillin.
0-7 days
- +1 more secondary outcomes
Study Arms (2)
Oral group
ACTIVE COMPARATORAfter 48 hours of intravenous antibiotics eligible neonates will switch to amoxicillin/clavulanic acid suspension for the remaining 5 days. When the oral suspension is well tolerated neonates can be discharged from hospital. In order to investigate the pharmacokinetic profile of oral amoxicillin/clavulanic acid serum levels will be measured.
Intravenous group
ACTIVE COMPARATORNeonates will complete the full course of antibiotics of 7 days intravenously in hospital following local protocol.
Interventions
Dose 75 mg/kg/day, (3dd 25 mg/kg). Concentration amoxicillin/clavulanic acid: 4:1
Eligibility Criteria
You may qualify if:
- Neonates (≥ 35+0 weeks, 0-28 days old, ≥ 2 kg)
- Probable bacterial infection defined as clinical symptoms and/or maternal risk factors and elevated inflammatory markers for which empiric broad-spectrum antibiotic treatment was initiated and needs to be continued for \> 48 hours
- Clinically well
- Toleration of oral feeding without overt vomiting
- Signed informed consent
You may not qualify if:
- Proven bloodstream infection
- Absence of blood culture
- Severe localized infection (meningitis, osteomyelitis, necrotizing enterocolitis)
- Severe clinical sepsis (compromised circulation, need for mechanical ventilation)
- Continuous need for a central venous line
- Severe hyperbilirubinemia exceeding the exchange level
- Parents inability to administer medication
- Major congenital or syndromic anomalies
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Franciscus Gasthuislead
- Erasmus Medical Centercollaborator
Study Sites (18)
Meander Medical Center
Amersfoort, Netherlands
Rijnstate Hospital
Arnhem, Netherlands
Amphia Hospital
Breda, Netherlands
IJsselland Ziekenhuis
Capelle aan den IJssel, Netherlands
Reinier de Graaf Gasthuis
Delft, Netherlands
Catharina Hospital
Eindhoven, Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
Groene Hart Ziekenhuis
Gouda, Netherlands
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands
Erasmus MC-Sophia Children's Hospital
Rotterdam, Netherlands
Franciscus Gasthuis
Rotterdam, Netherlands
Ikazia Ziekenhuis
Rotterdam, Netherlands
Maasstad Hospital
Rotterdam, Netherlands
Franciscus Vlietland
Schiedam, Netherlands
Haaglanden Medical Center
The Hague, Netherlands
Juliana Kinderziekenhuis-Haga Hospital
The Hague, Netherlands
Maxima Medisch Centrum
Veldhoven, Netherlands
Isala
Zwolle, Netherlands
Related Publications (2)
Keij FM, Kornelisse RF, Hartwig NG, van der Sluijs-Bens J, van Beek RHT, van Driel A, van Rooij LGM, van Dalen-Vink I, Driessen GJA, Kenter S, von Lindern JS, Eijkemans M, Stam-Stigter GM, Qi H, van den Berg MM, Baartmans MGA, van der Meer-Kappelle LH, Meijssen CB, Norbruis OF, Heidema J, van Rossem MC, den Butter PCP, Allegaert K, Reiss IKM, Tramper-Stranders GA. Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin-clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial. Lancet Child Adolesc Health. 2022 Nov;6(11):799-809. doi: 10.1016/S2352-4642(22)00245-0. Epub 2022 Sep 9.
PMID: 36088952DERIVEDKeij FM, Kornelisse RF, Hartwig NG, Mauff K, Poley MJ, Allegaert K, Reiss IKM, Tramper-Stranders GA. 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. BMJ Open. 2019 Jul 9;9(7):e026688. doi: 10.1136/bmjopen-2018-026688.
PMID: 31289068DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gerdien Tramper
Franciscus Gasthuis & Vlietland
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal investigator, MD, PhD
Study Record Dates
First Submitted
July 3, 2017
First Posted
August 14, 2017
Study Start
November 4, 2017
Primary Completion
June 15, 2021
Study Completion
July 15, 2021
Last Updated
August 24, 2021
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will share
Data will be made available on request through a repository and shared after consent of the principal investigator.