A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria. Clinical trial of beta-arteether versus quinine for the treatment of cerebral malaria in children in Yaounde, Cameroon.
The efficacy and safety of intramuscular artemotil (ARTECEF) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens. Rates for negative malaria smears one month after therapy were similar in both groups. Artemotil was a well-tolerated drug in the 48 patients in this study. It appears to be at least therapeutically equivalent to quinine for the treatment of pediatric cerebral malaria. It has the advantage of being able to be given intramuscularly once daily for only five days. One hundred and two children aged 0-10 years with cerebral malaria (Blantyre coma score of 2 or less) were randomly treated either with intramuscular arteether (3.2 mg/kg on Day 0, followed by 1.6 mg/kg on Days 1 to 4) or intravenous (i.v.) quinine dihydrochloride (20 mg of the salt/kg, followed by 10 mg of the salt/kg every 8 hr up to Day 6). Treatment with oral quinine sulfate (10 mg/kg every 8 hr) was substituted for i.v. quinine when the patient was able to take oral medicine. All patients were followed up in the hospital for 7 days; thereafter, they were treated as outpatients on Days 14, 21, and 28. Mortality rate, the main efficacy parameter, was 11.8% lower in the arteether treatment group than in the quinine group (15.7% versus 27.4%); however, the difference was not significant (P = 0.25). Means for fever clearance time, coma resolution time, and parasite clearance time were similar in the 2 treatment groups (42.2 +/- 34.9 hr; 34.8 +/- 18.8 hr, and 46.3 +/- 28.5 hr, respectively for arteether, versus 45.0 +/- 26.7 hr; 30.3 +/- 18.9 hr, and 40.7 +/- 18.9 hr, respectively, for quinine). At 28 days, the cure rates were 73.2% and 64.9% for the arteether and quinine treatment groups, respectively. Arteether is safe and therapeutically at least as effective as quinine for the treatment of cerebral malaria in children in Cameroon. Because of its ease of administration, arteether appears to be suited for use in the rural zones where monitoring facilities do not exist.
More trials with a larger number of participants are needed before a firm conclusion about the efficacy and safety of arteether can be reached.