Artemisinin-Based Antimalarial Combinations and Clinical Response in Cameroon
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

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
    

Detailed description: 
      Methodology Children of either gender, between 6 months (> 5kg) and 10 years of age, with
      acute uncomplicated P. falciparum infection, who fulfil all of the inclusion and have none of
      exclusion criteria will be enrolled in the study. They will be randomised to receive the
      three trial arms, i.e, Study Arm-A: artesunate-amodiaquine, Study Arm-B:
      dihydroartemisinin-piperaquine and Study Arm-C: artemether-lumefantrine at the ratio of 2:2:1
      and will be hospitalised over a 3-day period to facilitate the supervised administration of
      the study drugs and full clinical and laboratory assessment and observation of early adverse
      effects. On discharge, participants will be required to report to the study clinic on days 7,
      14, 21,28, 35 and 42 or at any other time when clinical sign(s)/symptom(s) of malaria is
      suspected. The number of participants is about 720 children

      Inclusion Criteria

        -  Children of either gender, aged between 6 months (> 5kg) and 10 years.

        -  Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using
           Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000
           parasites/μl.

        -  Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in
           the preceding 24 hours.

        -  Able to ingest tablets orally (either suspended in water or uncrushed with food).

        -  Willing to participate in the study with written assent from parent/guardian. Parental
           authorization will be obtained for children less than 8 years old and documented assent
           of parents/guardians for children 8-10 years.

        -  Willing and able to attend the clinic on stipulated regular follow-up visits.

      Exclusion Criteria

      • Any of the following "danger signs of severe malaria": Not able to drink or breast feed
      Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within
      previous 24 hours) Lethargic/unconscious

        -  Signs/symptoms indicating severe/complicated malaria according to WHO criteria (WHO
           definition).

        -  Concomitant illnesses, underlying chronic hepatic or renal disease, abnormal cardiac
           rhythm, hypoglycaemia, jaundice, respiratory distress,

        -  Serious gastrointestinal disease, severe malnutrition (W/H < 70%) or severe anaemia
           (haemoglobin < 5 g/dl).

        -  Known hypersensitivity to the study drugs.
    

Intervention name(s): Artesunate-Amodiaquine; Dihydroartemisinine-Piperaquine; Artemether-lumefantrine combination
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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®).; 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.; 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.
Other intervention name(s): CoArsucam; Duo-Cotecxin; CoArtem
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Piperaquine; Artemether, Lumefantrine Drug Combination; Amodiaquine; Artenimol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: malaria, cure rate, efficacy, safety