P. Knowlesi Trial of Artemether-lumefantrine vs Chloroquine

• Status: Completed
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Preliminary studies have supported the background efficacy of local standard anti-malarial medications in the treatment of uncomplicated knowlesi malaria, however there are no current WHO treatment guidelines for this infection. There are both health cost benefits to a more rapidly acting agent, and due to difficulties with microscopic identification there may be more effective treatment for all malaria species if an aligned treatment guideline could be supported. We are currently conducting a separate RCT using a similar protocol evaluating artesunate-mefloquine versus chloroquine for uncomplicated P. knowlesi malaria. However artemether-lumefantrine should also be compared against chloroquine due to the fact it is also a first line anti-malarial recommended in Malaysia, and there are potential differences in efficacy due to the different administration, absorption and half-life of artemether-lumefantrine.

The investigators aim to test whether the fixed combination of artesunate-mefloquine is superior to chloroquine in order to define the optimal treatment for both uncomplicated P. knowlesi infection in both adults and children in this region.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Menzies School of Health Research
• Collaborator: Ministry of Health, Malaysia
• Treatments: Artemether; Artemether-lumefantrine combination; Artemether, Lumefantrine Drug Combination; Artemisinins; Chloroquine; Chloroquine diphosphate; Lumefantrine

Criteria

Inclusion Criteria:

• Male and female patients at least 1 year of age and weighing more than 10kg.

• Microscopic diagnosis P. knowlesi (including diagnosis as P. malariae) or P. falciparum infection (any parasitaemia).

• Negative P. falciparum malaria rapid diagnostic test (histidine rich protein 2)

• Fever (temperature ≥37.5°C) or history of fever in the last 48 hours.

• Able to participate in the trial and comply with the clinical trial protocol.

• Written informed consent to participate in trial; thumbprint is required for illiterate patients, and written consent from parents/guardian for children below age of consent.

Exclusion Criteria:

• Clinical or laboratory criteria for severe malaria, including warning signs, requiring parenteral treatment according to modified WHO criteria (see Appendix 4)

• Parasitaemia > 20,000 /μL

• Inability to tolerate oral treatment

• Concomitant infection with any other malaria species

• Positive for P. falciparum histidine-rich-protein-2 by malaria rapid diagnostic test

• Pregnancy or lactation

• Unable or unwilling to use contraception during study period

• Known hypersensitivity or allergy to artemisinin derivatives

• Serious underlying disease (cardiac, renal or hepatic)

• Received anti-malarials in previous 2 months

• Previous psychiatric illness or epilepsy

• Previous episode of cerebral malaria