Severe malaria Infections and Infestations
Conditions
Interventions
In each domain (i.e. renal, cerebral, or severe anaemia complications of malaria) participants will be randomised 1:1 using an online tool to either:
1. High dose paracetamol (20mg/kg every 6 hours f
15mls/kg if axillary temperature is =37.5°C) for those with severe anaemia (severe anaemia domain)
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
3 Months to 11 Years
Inclusion criteria
Inclusion criteria: For all domains: 1. Aged >3 months and 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
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome is specific to each domain: 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. 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. 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
| Measure | Time frame |
|---|---|
| For all domains are readmissions to hospital and mortality to day 28 and day 90; grade 3 or 4 adverse events (AEs) during admission ascertained by questionnaire to parental/carer . Renal domain outcomes: 1. Creatinine at 24 hours (change from baseline, adjusted for baseline); Creatinine at 48 hours (change from baseline, adjusted for baseline); Creatinine at 72 hours (change from baseline, adjusted for baseline). Measurement are on laboratory biochemistry machines (real time or on stored plasma samples). Renal domain safety outcomes: 2. Change in Alanine transaminase (ALT) or Aspartate transaminase (AST) (liver enzymes) at 72 hours (adjusted for baseline) measured on biochemistry machines (real time or on stored plasma samples) 3. Adverse events (AEs) of any grade judged related to paracetamol assessed by the clinician 4. AEs of any grade causing a change in paracetamol administration Cerebral malaria domain outcomes: 1. Time to fully regain consciousness (BCS 5 (the maximum score)) assessed by the clinician on the clinical coma score assessment 2. Adverse events (AEs) of any grade judged related to anticonvulsants assessed by the clinician 3. Solicited AEs 4. Neurological sequelae by day 28 and day 90 assessed by the clinician using structure clinical assessment Severe anaemia domain outcomes: 1. Change in haemoglobin at 72 hours (measured by HaemoCue ® Hb 301 System, AngleHolm, Sweden) 2. Number of additional transfusions in the acute admission (recorded on prescription chart and case report forms) 3. Development of new profound anaemia (Hb<4g/dl) during acute admission or development of severe anaemia (Hb<6g/dl) post discharge measured by HaemoCue ® Hb 301 System, AngleHolm, Sweden) | — |
Countries
Congo, Democratic Republic, Ghana, Kenya, Mozambique, Uganda, Zambia
Contacts
Public ContactEmmanuel Oguda
Outcome results
None listed