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Randomized Trial on Effectiveness of ACTs in Ghana

Phase 4
Terminated
Conditions
Malaria, Falciparum
Interventions
Registration Number
NCT00374205
Lead Sponsor
Bernhard Nocht Institute for Tropical Medicine
Brief Summary

The purpose of this study is to compare the effectiveness and safety of two Artemisinin Combination Therapies (ACTs) for the treatment of children with uncomplicated Plasmodium falciparum malaria

Detailed Description

Childhood mortality related to Plasmodium falciparum malaria is on the rise with more than 1 million deaths per year in Sub-Saharan Africa. In the context of growing drug-resistance to antimalarials health officials are calling for rapid replacement of failing drugs by combining antimalarial drugs. Artemisinin Combination Antimalarial Therapies (ACTs) are in the focus of malaria control programmes and are recommended for first-line treatment in African countries. ACTs have been reported to be highly effective as artemisinin derivatives cause a rapid and substantial decrease in the parasite load when used for treating patients with malaria and resistance to artemisinin is still lacking. However, the short half-lives of artemisinins result in frequent recrudescent infections when used alone and therefore, much interest lays on the choice of the combination partner drug. ACTs also have been proposed as a means of reducing transmission by the reduction of gametocytes and of delaying the spread of drug resistance and prolonging the therapeutic life span of. Nevertheless, drug resistance of parasites to the respective partner drug is a matter of concern. Artesunate-amodiaquine (AQ) and artemether-lumefantrine (AL) are two registered fixed-dose artemisinin combination chemotherapies used in Africa which are GMP-manufactured at industrial scale. There is still limited data from randomised, controlled trials to support the general effectiveness of these two ACTs in Africa, including Ghana. More data is needed to compare these two therapies to make evidence-based first-line treatment decisions. Importantly, it is difficult to predict how combination therapy may affect the spread of drug resistance and monitoring drug resistance markers should be embedded in these trials to guide drug policy decision.

The aim of this open-labelled, randomised drug trial is to compare the effectiveness and safety of artesunate-amodiaquine (Arsucam®) against artemether plus lumefantrine (Coartem®) for the treatment of children under five years of age with uncomplicated Plasmodium falciparum malaria.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
245
Inclusion Criteria
  • Male and female outpatients aged 6 months to 59 months
  • Absence of severe malnutrition
  • A slide-confirmed P. falciparum asexual parasitaemia between 2,000/µl and 200,000/µl
  • A measured axillary temperature ≥ 37.5 °C or rectal/tympanic temperature ≥ 38.0 °C
  • Absence of general danger signs (unable to drink; repeated vomiting; recent history of convulsions; lethargic or unconscious state; unable to stand up or to sit)
  • Ability to tolerate oral therapy
  • Permanent residence in study area
  • Informed consent by the legal representative of the subject, if possible, the parents
Exclusion Criteria
  • Adequate anti-malarial treatment within the previous 7 days
  • Antibiotic treatment for a current infection
  • Previous participation in a clinical trial
  • Haemoglobin < 5 g/dl
  • Leucocyte count: > 15000/µl
  • Mixed plasmodial infection
  • Severe malaria as defined by WHO recommendations
  • Any other severe underlying disease (cardiac, renal, hepatic diseases, malnutrition, known HIV infection) or concomitant disease masking assessment of response
  • History of allergy or intolerance against trial medication

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ALArtemether-LumefantrineArtemether plus Lumefantrine 6 dose 3 days treatment
ASAQArtesunate plus AmodiaquineArtesunate plus Amodiaquine
Primary Outcome Measures
NameTimeMethod
Clinical and PCR-controlled parasitological cure rate at day 2828 days
Secondary Outcome Measures
NameTimeMethod
Molecular Drug Resistance Markers28 days
Clinical and PCR-controlled parasitological cure rate at day 1414 days
Effect on anaemia28 days
Recrudescence and Reinfection28 days
Effects on Gametocytemia28 days
Acceptance of Therapies7 days
Incidences of malaria episodes over a follow-up period of 1 year12 months

Trial Locations

Locations (1)

Agogo Presbyterian Hospital

🇬🇭

Agogo, Asante Akim North District, Ghana

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