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.

Condition	Intervention	Phase
Cerebral Malaria	Drug: Intrarectal quinine	Phase III

Further Study Details: 

Primary Outcomes: Parasite clearance time
Secondary Outcomes: Fever clearance time; Coma recovery time; Time to sit unsupported; Time to begin oral intake; Mortality; Neurological sequelae; Adverse drug events
Expected Total Enrollment:  108

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.

Ages Eligible for Study:  6 Months   -   5 Years,  Genders Eligible for Study:  Both

Criteria

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.

Uganda
      Mulago Hospital, Kampala,  7051,  Uganda

Study chairs or principal investigators

Jane Achan, MBChB,  Principal Investigator,  Department of Paediatrics and Child Health, Makerere University   

Study ID Numbers:  2001/HD11/524/RQ
Last Updated:  August 3, 2005
Record first received:  July 26, 2005
ClinicalTrials.gov Identifier:  NCT00124267
Health Authority: Uganda: National Council for Science and Technology
ClinicalTrials.gov processed this record on 2005-08-23