In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy

Global Emerging Infections Surveillance and Response System

Status and phase: Completed; Phase 4

Conditions: Malaria

Treatments: Drug: Artemether Lumefantrine; Drug: Mefloquine; Drug: Artesunate

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT01976780

WRAIR1935

Details and patient eligibility

About

This study aims to assess the degree of artemisinin resistance in adult and pediatric subjects presenting with uncomplicated falciparum malaria in Western Kenya. The study treatments will be Artemether Lumefantrine (AL) and Artesunate Mefloquine (ASMQ).

Full description

Data generated by this study will provide a snapshot of the current situation regarding P. falciparum sensitivity to ACTs in Western Kenya. By having subjects in one of the study arms receive artesunate and then the partner drug after completion of the artemisinin phase will enable the accurate evaluation of the artemisinin derivative without the confounding influence of the partner drug. Sequential administration of the components of an ACT drug is recognized by the WHO as one of the ways in which ACTs can be administered. There will be close follow-up of the subjects throughout the duration of the study, and as such, subjects who fail to respond adequately will receive prompt rescue treatment. Since it is largely expected that most subjects in Western Kenya will have satisfactory responses to ACTs, data from this study will provide baseline information regarding parasite characteristics when compared to data from Thailand, an area that has reported resistance to ACTs. This, in turn, will potentially enable the identification of key markers, both in the host and the parasite, that may assist in the early detection of resistance, and also to better understand the development of resistance to ACTs. As such, the data generated from this study, both on its own and when compared to and pooled with data from similar studies that will be conducted in Peru and Thailand, will potentially inform both local and international policy regarding ACT use for the treatment of uncomplicated P. falciparum malaria.

Enrollment: 118 patients

Sex: All

Ages: 6 months to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult/child aged between 6 months and 65 years inclusive (minimum weight 11kg), presenting with a measured temperature of ≥37.5 C, or history of fever within 24 hours prior to presentation
• Mono-infection with Plasmodium falciparum
• Baseline parasitemia of 2000 - 200,000 asexual parasites/µl
• Ability to provide informed consent
• Willingness and ability to comply with the study protocol for the duration of the study
• Willingness to remain in the hospital for 3 days

Exclusion criteria

• Presence of signs of severe malaria as defined by WHO
• Presence of severe anemia, defined as hemoglobin level below 6 g/dl
• Presence of mixed Plasmodium infection, or mono-infection of non-falciparum Plasmodium
• Inability to take oral medication
• History of allergy or contraindications to the study treatments
• Lactating or pregnant females
• Any condition that the investigator feels will result in an unfavorable outcome should the potential subject participate in the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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118 participants in 2 patient groups

AS/MQ

Active Comparator group

Description:

Treatment of P.falciparum mono-infection with 4 mg/kg of Artesunate daily for three days followed by 25mg/kg of Mefloquine split over two days.

Treatment:

Drug: Artesunate

Drug: Mefloquine

AL

Active Comparator group

Description:

Treatment of P. falciparum mono-infection with Artemether Lumefantrine administered at the standard dosage according to pre-defined weight bands (5-14 kg: 1 tablet; 15-24 kg: 2 tablets; 25-34 kg: 3 tablets; and \> 34 kg: 4 tablets) given twice a day for 3 days.

Treatment:

Drug: Artemether Lumefantrine