Randomized Trial on Effectiveness of ACTs in Ghana

NCT ID: NCT00374205

Last Updated: 2007-11-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 245 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2007-10-31

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.

Conditions

Malaria, Falciparum

Keywords

Ghana; Effectiveness; Safety; Drug-Resistance; ACT; Coartem; Arsucam

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AL

Artemether plus Lumefantrine 6 dose 3 days treatment

Group Type: EXPERIMENTAL

Artemether-Lumefantrine

Intervention Type: DRUG

Artemether 20 mg/Lumefantrine 120mg fixe-dose-combination tablets: 3 days twice daily weight-adjusted dosing according to manufacturer

ASAQ

Artesunate plus Amodiaquine

Group Type: ACTIVE_COMPARATOR

Artesunate plus Amodiaquine

Intervention Type: DRUG

Artesunate 50 mg and Amodiaquine 153 mg co-blister tablets: 3 days once daily weight-adjusted dosing according to manufacturer

Interventions

Artesunate plus Amodiaquine

Artesunate 50 mg and Amodiaquine 153 mg co-blister tablets: 3 days once daily weight-adjusted dosing according to manufacturer

Intervention Type: DRUG

Artemether-Lumefantrine

Artemether 20 mg/Lumefantrine 120mg fixe-dose-combination tablets: 3 days twice daily weight-adjusted dosing according to manufacturer

Intervention Type: DRUG

Other Intervention Names

Arsucam®; Coartem®

Eligibility Criteria

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Presbyterian Health Service (PHS)

UNKNOWN

Sponsor Role: collaborator

Kumasi Centre for Collaborative Research (KCCR)

OTHER

Sponsor Role: collaborator

School of Medical Sciences Kumasi (SMS/KNUST)

UNKNOWN

Sponsor Role: collaborator

Bernhard Nocht Institute for Tropical Medicine

OTHER_GOV

Sponsor Role: lead

Principal Investigators

Daniel Ansong, MD

Role: PRINCIPAL_INVESTIGATOR

School of Medical Science (SMS), Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana

Locations

Agogo Presbyterian Hospital

Agogo, Asante Akim North District, Ghana

Countries

Ghana

References

Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, Rwakimari JB, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, Staedke SG. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials. 2006 May;1(1):e7. doi: 10.1371/journal.pctr.0010007. Epub 2006 May 19.

Reference Type: BACKGROUND

PMID: 16871329 (View on PubMed)

Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, Greenwood BM, Whitty CJ. Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet. 2005 Apr 23-29;365(9469):1474-80. doi: 10.1016/S0140-6736(05)66417-3.

Reference Type: BACKGROUND

PMID: 15850631 (View on PubMed)

Makanga M, Premji Z, Falade C, Karbwang J, Mueller EA, Andriano K, Hunt P, De Palacios PI. Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data. Am J Trop Med Hyg. 2006 Jun;74(6):991-8.

Reference Type: BACKGROUND

PMID: 16760509 (View on PubMed)

Price RN, Uhlemann AC, van Vugt M, Brockman A, Hutagalung R, Nair S, Nash D, Singhasivanon P, Anderson TJ, Krishna S, White NJ, Nosten F. Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clin Infect Dis. 2006 Jun 1;42(11):1570-7. doi: 10.1086/503423. Epub 2006 Apr 26.

Reference Type: BACKGROUND

PMID: 16652314 (View on PubMed)

Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005 Oct 15;41(8):1079-86. doi: 10.1086/444460. Epub 2005 Sep 13.

Reference Type: BACKGROUND

PMID: 16163624 (View on PubMed)

Sidhu AB, Uhlemann AC, Valderramos SG, Valderramos JC, Krishna S, Fidock DA. Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J Infect Dis. 2006 Aug 15;194(4):528-35. doi: 10.1086/507115. Epub 2006 Jul 11.

Reference Type: BACKGROUND

PMID: 16845638 (View on PubMed)

Related Links

http://www.kccr.de/kccr/

Homepage of the Kumasi Centre for Collaborative Research (study site)

Other Identifiers

01KA22062006

Identifier Type: -

Identifier Source: org_study_id