Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria

Study Overview
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Brief Summary
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Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. Studies of the efficacy of intrarectal quinine in the treatment of cerebral malaria are limited. The study aims to establish the efficacy of intrarectal quinine in the treatment of childhood cerebral malaria.

Detailed Description
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Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. A few studies in Francophone Africa have reported clinical efficacy and tolerance of intrarectal quinine. Although the studies were randomized trials, they were not blinded and did not use the WHO definition of cerebral malaria as selection criteria. The current study aims to establish whether intrarectal quinine is as effective and as safe as intravenous quinine in the treatment of childhood cerebral malaria. To address the shortcomings of the Francophone African studies, the investigators have designed a randomized, double blind placebo controlled clinical trial to include patients who meet the WHO definition of cerebral malaria. Hypothesis: Intrarectal quinine (15mg/kg every 8 hours) given to children with cerebral malaria, will lead to a shorter parasite clearance time (39.9 hours) than intravenous quinine (55.0 hours). The investigators calculated a sample size of 54 patients in each group for 90% power and 95% confidence. In the calculation, the researchers assumed that the children receiving intrarectal quinine would have a mean parasite clearance time of 39.9 (SD 24.3) hours and those receiving intravenous quinine would have a mean parasite clearance time of 55.0(SD 24.3) hours (27.5% effect size), according to a study by Aceng, Byarugaba and Tumwine in the same hospital.

Official Title
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Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria: a Randomized Clinical Trial

Conditions
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Cerebral Malaria

Intervention / Treatment
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* Drug: Intrarectal quinine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 6 months to 5 years admitted to Mulago hospital during the study period who satisfy the World Health Organization (WHO) case definition of cerebral malaria (Unarousable coma lasting more than 30 minutes after a seizure, with peripheral asexual P.falciparum parasitaemia and absence of other causes of coma) and whose caretakers give informed consent. Exclusion Criteria: Patients with diarrhea (more than 4 motions/24 hours) Any recent anal pathology (such as rectal bleeding, rectal prolapse) Documented quinine treatment in previous 48 hours.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Intrarectal quinine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite clearance time |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fever clearance time |  |  | 
| Coma recovery time |  |  | 
| Time to sit unsupported |  |  | 
| Time to begin oral intake |  |  | 
| Mortality |  |  | 
| Neurological sequelae |  |  | 
| Adverse drug events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral, malaria, intra-rectal, quinine, children, Uganda, efficacy, safety