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Severe malaria in African children: A randomised clinical trial with an adaptive desig

Not Applicable
Conditions
Severe malaria
Infections and Infestations
Registration Number
ISRCTN79071535
Lead Sponsor
Imperial College London
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing
Sex
All
Target Recruitment
450
Inclusion Criteria

For all domains:
1. Aged >3 months and <12 years
2. Admitted to the paediatric ward in the last 24 hours
3. Current or recent evidence of malaria (slide or rapid diagnostic test (RDT) positive in this admission)
4. Guardian willing to provide consent

Additional domain-specific inclusion criteria:

Renal domain:
1. Creatinine >1.5xULN on point-of-care assay or laboratory test at screening
2. Meet one of the current WHO severity criteria (clinical or laboratory (where these tests are done routinely)) (Group 1 and 2 from the recent WHO reclassification of severe malaria))

Cerebral malaria domain:
EITHER
1. One or more reported seizures in the current episode of illness and altered consciousness (BCS=4) at screening
OR
2. Presence of coma (BCS =2) at screening regardless of history

Severe anaemia domain:
1. Hb <6g/dl
2. One or more or the following severity signs: Hb<4g/dl, prostration, impaired consciousness, respiratory distress, history of passing red or coca-coloured urine in this illness

Exclusion Criteria

Renal domain:
1. Received paracetamol within 6 hours of screening or between screening and randomisation
2. Known allergy to paracetamol
3. Severe malnutrition (middle upper arm circumference MUAC<11.5cm)

Cerebral malaria domain:
1. Received an anticonvulsant within 6 hours of screening or between screening and randomisation.
2. Known cerebral palsy or significant neuro-development delay

Severe anaemia domain:
1. Known congenital or valvular heart disease (not surgically corrected)

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Primary outcome is specific to each domain:<br><br>Renal Domain: Area Under the Curve (AUC) for creatinine over the first 72 hours from Randomisation. Creatinine will be measured by a laboratory biochemistry machine on stored plasma samples taken at randomisation (treated as time 0/baseline), 24, 48 and 72 hours. The AUC will be calculated from these measurements.<br><br>Cerebral Malaria domain: the number of witnessed seizures by medical staff which result in starting or changing anticonvulsant medication by 72 hours. The child will have regular scheduled, and where clinically indicated non-scheduled, assessments by the trial team which will assess for witnessed seizures since the last assessment and will be recorded in the CRF.<br><br>Severe Anaemia domain: change in haemoglobin at 24 hours (adjusted for baseline). Haemoglobin will be measured using a point-of-care analyser (HaemoCue ® Hb 301 System, AngleHolm, Sweden) at randomisation (treated as time 0/baseline) and at 24 hours.
Secondary Outcome Measures
NameTimeMethod
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