Severe malaria Infections and Infestations Plasmodium falciparum malaria
Conditions
Interventions
Sevuparin is given as three infusions at 0, 8 and 16 hours after enrolment. Initially two cohorts of two participants will receive a dose of 1.5 mg/kg/dose with the plan to escalate to a cohort of two
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged between 3 months and 12 years admitted to the paediatric wards within the last 24 hours 2. Current or recent evidence of P. falciparum malaria (slide or rapid diagnostic test (RDT) positive) 3. Clinical evidence of severe malaria: impaired consciousness: coma (inability to localize painful stimulus) or prostration (inability to sit unsupported for those above 6 months) or deep breathing 4. Lactate >2 mmol/l 5. Guardian or parent willing and able to provide consent
Exclusion criteria
Exclusion criteria: 1. Clinical evidence or a history of a bleeding/coagulation disorder 2. A comorbidity which clinician believes has a significant risk of poor outcome e.g. malignancy, end-stage renal failure, major cardiac condition 3. Thrombocytopenia (platelet count <25 x10(9)/l)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Activated partial thromboplastin time (APTT) >2.5x upper limit of normal (ULN) (Common Toxicity Criteria grade 3), measured by the Sysmex semi-automated blood coagulation analyzer (CA-104), at 1 hour post any sevuparin dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: 1. Change in lactate measured by Stat Strip Xpress Hospital meter from 0 to 8 hours 2. Macroscopic presence of mature infected erythrocytes on the blood films at 8 and 24 hours 3. Parasite clearance time measured by microscopy during hospital admission 4. Change in sublingual microcirculation measured using Braedius cytocam for microcirculation at 0, 9 and 17 hours Safety: 1. APTT (absolute level and grade) measured using the Sysmex semi-automated blood coagulation analyzer (CA-104) at 24 hours post enrolment 2. Development of abnormalities of coagulation indices of grade 2 and above measured using the Sysmex semi-automated blood coagulation analyzer (CA-104) at 0,1, 9, 17 and 24 hours 3. Neurological sequelae assessed by the Kilifi Developmental Index until day 28 4. Mortality measured using clinical assessment until day 28 5. Serious adverse events (mortality, readmissions and prolongation of admission) measured by clinical observation recorded on the case report forms until day 28 6. Grade 3/4 adverse events measured by clinical observation recorded on the case report forms until day 28 | — |
Countries
Kenya, Zambia
Contacts
Public ContactEmmanuel Oguda
Outcome results
None listed