Efficacy of Artesunate + Amodiaquine Versus Artemether-lumefantrine for Falciparum Malaria in Zanzibar, 2005 (ACOII)
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|ClinicalTrials.gov Identifier: NCT03768908|
Recruitment Status : Completed
First Posted : December 7, 2018
Last Update Posted : December 7, 2018
The primary objective of the study was to determine the PCR-APCR up to day 42 in children <60 months of age, weighing ≥5kg with uncomplicated malaria, treated with either artesunate+ amodiaquine (ASAQ) or artemether-lumefantrine (AL; Coartem®).
Secondary objectives included: clinical and laboratory assessment of drug tolerability and safety, evaluation of possible correlation between drug bioavailability and clinical outcome, comparison of efficacy data with the pre-implementation "ACO I" study, parasite and fever clearance, gametocyte carriage, and possible selection of mutations related to quinoline resistance.
|Condition or disease||Intervention/treatment||Phase|
|Plasmodium Falciparum Malaria||Drug: Artemether-lumefantrine Drug: Artesunate + Amodiaquine||Phase 4|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||359 participants|
|Intervention Model Description:||A multicentre randomised comparative clinical trial of the efficacy of ASAQ versus AL for the treatment of uncomplicated childhood Plasmodium falciparum malaria.|
|Masking:||None (Open Label)|
|Masking Description:||No blinding was done due to the different drug formulations and regimens.|
|Official Title:||A Multicentre Randomised Comparative Clinical Trial of the Efficacy of Artesunate + Amodiaquine Versus Artemether-lumefantrine (Coartem®) for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Zanzibar|
|Actual Study Start Date :||January 5, 2005|
|Actual Primary Completion Date :||July 11, 2005|
|Actual Study Completion Date :||July 11, 2005|
Active Comparator: Treatment with artesunate + amodiaquine
Co-administration of a daily dose of artesunate (Arsumax) 4mg/kg and amodiaquine (Flavoquine) 10mg/kg for 3 days, under direct observation. Children <12months <10kg: artesunate (Arsumax) 50mg - 0.5tab/day + amodiaquine (Flavoquine) 153mg - 0.5tab/day; Children 12-59months 10-20kg: artesunate (Arsumax) 50mg - 1 tab/day + amodiaquine (Flavoquine) 153mg 1 tab/day.
Drug: Artesunate + Amodiaquine
Three day treatment with Artesunate + Amodiaquine, co-administered, a dose a day under direct observation
Other Name: ASAQ
Active Comparator: Treatment with artemether-lumefantrine (Coartem®)
Artemether-lumefantrine (Coartem®) - artemether 1.3mg/kg + lumefantrine 4mg/kg administered twice daily, both doses under direct observation either in the clinic or in the patient's home. Children <60 months, 5-14kg: 1 tab/dose; Children <60 months >14kg: 2 tabs/dose.
Three day treatment with Artemether-lumefantrine, 2 doses a day under direct observation
Other Name: Coartem®
- PCR adjusted parasitological cure rates by day 42 [ Time Frame: 42 days ]Comparing PCR adjusted parasitological cure rate (PCR-APCR) between the two treatment options up to day 42. Parasitological cure will be adjusted using PCR genotyping of msp2 marker. Recrudescence is defined as the presence of at least one matching allelic band, and reinfection as the absence of any matching allelic band on day 0 and day of recurring parasitaemia. Patients with recurrent parasitaemia having missing filter paper sample or negative PCR results will be considered uncertain with regards to PCR adjusted outcome.
- The clinical and parasitological response outcome (i.e. cure rates) on days 14, day 28 and 42. [ Time Frame: 42 days ]Comparing proportion of response outcomes according to standard WHO classification i.e., cure rates on days 14, day 28 and 42. Defined as the absence of both re-parasitaemia and clinical symptoms suggestive of severe malaria during follow-up to the respective days.
- Clinical and laboratory assessment of drug tolerability and safety i.e., incidence of adverse events. [ Time Frame: 42 days ]Proportion of patients reporting any adverse event (AE) in the two study arms. The intensity of an adverse event was determined according to the following definitions: mild, moderate, severe, unknown. AEs were be categorized according to if there is a likely causal relationship between the event and the medical products: probably, possibly, unlikely.
- Fever clearance in the two study arms [ Time Frame: 42 days ]Fever clearance was determined by a medical doctor/officer who measured the patient's axillary temperature using an electronic thermometer and took a detailed clinical history as well as performed a clinical examination. All details were recorded in the CRF.
- Parasite clearance and gametocyte carriage in the two study arms [ Time Frame: 42 days ]Clearance of parasites and gametocyte carriage were determined by Giemsa stained thick blood films were examined using electrical or sunlight microscope at the study site by an experienced microscopist. The number of parasites were calculated as the number of parasites seen against 200 leucocytes in the thick blood film and recorded in the CRF for the correct occasion. The slides were stored for quality controls, 10% of all slides were double-checked centrally.
- Proportion of mutations related to Quinoline resistance at day0 and day of recurrent infection in the two study arms [ Time Frame: 42 days ]Proportions of single nucleotide polymorphisms at pfmdr1 Y86N and pfcrt K76T determined by established AluI restriction-based PCR-RFLP.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03768908
|Principal Investigator:||Johan Stromberg||Karolinska Institutet|
|OverallOfficial:||Mwinyi I Msellem||Zanzibar Malaria Control Programme|
|OverallOfficial:||Andreas Martensson||Karolinska Institutet|