First Line Antimicrobials in Children With Complicated Severe Acute Malnutrition
NCT ID: NCT03174236
Last Updated: 2020-05-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
2000 participants
INTERVENTIONAL
2017-09-04
2020-12-31
Brief Summary
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Detailed Description
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A further area where evidence for policy is lacking is the use of metronidazole in severely malnourished children. The WHO guidelines recommend "Metronidazole 7.5 mg/kg every 8 h for 7 days may be given in addition to broad-spectrum antibiotics; however, the efficacy of this treatment has not been established in clinical trials." Metronidazole is effective against anaerobic bacteria, small bowel bacterial overgrowth, Clostridium difficile colitis and also Giardia, which is common amongst children with SAM. Small cohort studies of metronidazole usage suggest there may be benefits for nutritional recovery in malnourished children. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also rarely cause liver and neurological toxicity.
This multi-centre clinical trial will assess the efficacy of two interventions, ceftriaxone and metronidazole, on mortality and nutritional recovery in sick, severely malnourished children in a 2x2 factorial design. There will also be an analysis of antimicrobial resistance and an economic analysis. To extend our understanding of metronidazole and ceftriaxone pharmacokinetics, additional pharmacokinetic data for the dosing schedule used in the trial will be collected from 120 participants in a sub-study. The trial will be conducted at Kilifi County Hospital, Coast General Hospital, Mbagathi Hospital in Kenya and Mbale Regional Referral Hospital in Uganda. The trial will assess antimicrobial resistance that is carried by children in their intestines and in invasive bacterial isolates. A further sub-study will examine the relative costs of care for SAM for health facilities and for families, including antimicrobial usage will also be assessed. Clear data on the benefits, risks and costs of these antimicrobials will influence policy on case management and antimicrobial stewardship in this vulnerable population.
Conditions
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Study Design
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RANDOMIZED
FACTORIAL
TREATMENT
QUADRUPLE
Ceftriaxone and penicillin + gentamicin will not be masked.
Study Groups
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Ceftriaxone
Arm 1 IV Ceftriaxone: Participants in this group receive 80mg/kg IV ceftriaxone once a day for a minimum of 48 hours and a usual maximum of seven days.
Ceftriaxone
Ceftriaxone a third-generation cephalosporin. Ceftriaxone is active against a broad spectrum of Gram positive and Gram negative bacteria.
Benzyl penicillin plus gentamicin
Arm 2 IV Benzyl penicillin plus gentamicin (usual care): Participants in this group receive 50 000 U/kg IV benzyl penicillin every six hours for a minimum of two days and a maximum of seven days.
Benzyl penicillin
The currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin.
Gentamicin
The currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin.
Metronidazole
Arm 1 Metronidazole: Participants receive 10 to 16 mg/kg oral metronidazole twice a day for seven days.
Metronidazole
The WHO guidelines recommend that Metronidazole may be given in addition to broad-spectrum antibiotics, "however, the efficacy of this treatment has not been established in clinical trials."
Placebo
Arm 2 Placebo: Participants receive an oral placebo dose to match that for Metronidazole twice a day for seven days.
Placebo
Suspension manufactured to match metronidazole
Interventions
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Ceftriaxone
Ceftriaxone a third-generation cephalosporin. Ceftriaxone is active against a broad spectrum of Gram positive and Gram negative bacteria.
Benzyl penicillin
The currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin.
Metronidazole
The WHO guidelines recommend that Metronidazole may be given in addition to broad-spectrum antibiotics, "however, the efficacy of this treatment has not been established in clinical trials."
Placebo
Suspension manufactured to match metronidazole
Gentamicin
The currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin.
Eligibility Criteria
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Inclusion Criteria
* Severe malnutrition defined as:
* kwashiorkor at any age or:
* for children between 2 to 5 months: MUAC \<11cm or weight-for length Z score \<-3
* for children between 6 to 59 months: MUAC \<11.5cm or weight-for length Z score \<-3
* for children between 5 to 13 years: MUAC \<11.5cm or BMI-for-age Z score \<-3
* Admitted to hospital and eligible for intravenous antibiotics according to WHO guidelines
* Planning to remain within the hospital catchment area and willing to come for specified visits during the 90 day follow up period
* Informed consent provided by the parents/guardian
Exclusion:
* Known allergy or contraindication to penicillin, gentamicin, ceftriaxone or metronidazole
* A specific and documented clinical indication for another class of antibiotic
* Previously enrolled in this study
2 Months
13 Years
ALL
No
Sponsors
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University College, London
OTHER
London School of Hygiene and Tropical Medicine
OTHER
Swansea Trials Unit
UNKNOWN
Kenya Medical Research Institute
OTHER
KEMRI-Wellcome Trust Collaborative Research Program
OTHER
University of Oxford
OTHER
Responsible Party
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Principal Investigators
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James A Berkely, FRCPCH
Role: PRINCIPAL_INVESTIGATOR
KEMRI/Wellcome Trust Research Programme & University of Oxford
Locations
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Kemri Wellcome Trust Research Programme
Kilifi, Coast Province, Kenya
Kilifi County Hospital
Kilifi, Coast, Kenya
KEMRI WT Clinical Trials Facility
Kilifi, , Kenya
Kilifi County Hospital
Kilifi, , Kenya
Coast General Hospital - Study site
Mombasa, , Kenya
Mbagathi District Hospital
Nairobi, , Kenya
Mbagathi Hospital
Nairobi, , Kenya
Mbale Regional Referral Hospital
Mbale, , Uganda
Countries
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References
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Related Links
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Pocket book of hospital care for children Guidelines for the management of common illnesses with limited resources Author: World Health Organization
Other Identifiers
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1-17
Identifier Type: OTHER
Identifier Source: secondary_id
105431/Z/14/Z
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
KEMRI/SERU/CGMR-C/063/3399
Identifier Type: -
Identifier Source: org_study_id
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