Randomized Trial on Effectiveness of ACTs in Ghana

Bernhard Nocht Institute for Tropical Medicine

Status and phase

Terminated

Phase 4

Conditions

Malaria, Falciparum

Treatments

Drug: Artemether-Lumefantrine

Drug: Artesunate plus Amodiaquine

Study type

Interventional

Funder types

Other

Identifiers

NCT00374205

01KA22062006

Details and patient eligibility

About

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

Full 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.

Enrollment

245 patients

Sex

All

Ages

6 to 59 months old

Volunteers

No Healthy Volunteers

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