Artemisinin-Based Antimalarial Combinations and Clinical Response in Cameroon

Summary

To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in 720 children with acute uncomplicated P. falciparum malaria, in two different endemic ecological areas - Savanna and equatorial forest regions of Cameroon.

We have set as specific objectives:

* To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 14 and 28 days follow up period in children with acute uncomplicated P. falciparum malaria in two different endemic areas.
* To evaluate the safety of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in children with acute uncomplicated P. falciparum malaria.
* To determine parasite clearance time (PCT) and fever clearance time (FCT) following the administration of the three trial regimens.
* To investigate the treatment response based on WHO criteria (WHO, 2003) in patients in all groups after trial.
* To investigate the Single Nucleotide Polymorphisms (SNPs) and microsatellite markers of genes associated with drug resistance

Conditions

• Malaria

Interventions

DRUG

Artesunate-Amodiaquine

Pharmacology: Amodiaquine is effective against the erythrocytic stages of all four species of P. falciparum. Amodiaquine accumulates in the parasite's lysosomes and prevents breakdown of haemoglobin on which the parasite depends for its survival. Artesunate is a water-soluble hemisuccinate derivative of artemisinin. Artesunate and its active metabolite dihydroartemisinin are potent blood schizonticides, active against the ring stage of the parasite. The fixed-dose combination dihydroartemisinin-piperaquine has a cost advantage over other ACTs that brings it within reach of many, making it a potential best candidate for deployment in Africa and other poor countries. The drug is currently produced in China (Duo-cotecxin®).

DRUG

Dihydroartemisinine-Piperaquine

It is a bisquinoline antimalarial drug (1,3-bis\[1-(7-chloro-4 quinolyl)-4- piperazinyl\]-propane) that was first synthesised in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. A number of Chinese research groups documented that it was at least as effective as, and better tolerated than, chloroquine against falciparum and vivax malaria. With the development of piperaquine-resistant strains of P. falciparum and the emergence of the artemisinin derivatives, its use declined during the 1980s. However, during the next decade, piperaquine was rediscovered by Chinese scientists as one of a number of compounds suitable for combination with an artemisinin derivative.

DRUG

Artemether-lumefantrine combination

CoArtem® is an oral, fixed combination of artemether- a derivative of artemisinin and lumefantrine- a novel molecule developed by the Academy of Military Medical Sciences (AMMS) in Beijing. It is the only co-formulated ACT approved by WHO and is currently available through WHO at a negotiated public sector price. Both compounds are effective as single agents. However, recrudescence is common with artemether and lumefantrine has a slow onset of action. A fixed combination tablet (20 mg artemether/120 mg lumefantrine) has therefore been developed. Fixed combination therapy improves compliance and has the advantage of carrying a lower risk of selecting drug resistant strains. No resistance to either component has been observed to date.

Sponsors & Collaborators

• World Health Organization

  collaborator OTHER

• Gates Malaria Partnership

  collaborator OTHER

• University of Yaounde 1

  lead OTHER

Principal Investigators

• Wilfred F Mbacham, ScD · University of Yaounde 1

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

120 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-03-31

Primary Completion

2014-04-30

Completion

2015-04-30

Countries

• Cameroon

Study Locations