Clinical trial NCT01976780: In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy
Official title: In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy in Kisumu County, Western Kenya
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: Malaria
P. falciparum mono infection
Early Treatment Failure
Late Treatment Failure
Lead sponsor: Global Emerging Infections Surveillance and Response System
Sponsor class: FED
Collaborators: name: United States Army Medical Unit - Kenya
name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2013-11-06
Enrollment: 118
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Parasitological clearance rates by microscopy
timeFrame: 72 hours
Secondary outcomes:
measure: Parasitological clearance rates by quantitative Polymerase Chain Reaction (PCR)
timeFrame: 72 hours
measure: PCR-adjusted treatment efficacy of AL and AS/MQ
timeFrame: 42 days
measure: Antimalarial drug sensitivity responses and molecular genotyping
timeFrame: 42 days
measure: Identify common specific genetic determinants of artemisinin resistance derived from parasite populations
timeFrame: 42 days
measure: Gametocyte carriage in patients with uncomplicated malaria after treatment
timeFrame: 42 days
measure: Catalog parasite samples
timeFrame: 42 days
measure: Pharmacokinetic parameters associated with ACT failure
timeFrame: 42 days
Other outcomes:
measure: Parasite clearance rates and immune response in semi-immune population
timeFrame: 42 days
measure: Production of microbiocidal molecules
timeFrame: 42 days
measure: Acute cytokine response
timeFrame: 42 days
Locations:
city: Kisumu
country: Kenya
facility: Walter Reed Project, Kombewa Clinic
Study officials:
affiliation: GEIS
name: James F Cummings, MD
role: STUDY_CHAIR
affiliation: Kenya Medical Research Institute/Walter Reed Project
name: Ben Andagalu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Odhiambo G, Bergmann-Leitner E, Maraka M, Wanjala CNL, Duncan E, Waitumbi J, Andagalu B, Jura WGZO, Dutta S, Angov E, Ogutu BR, Kamau E, Ochiel D. Correlation Between Malaria-Specific Antibody Profiles and Responses to Artemisinin Combination Therapy for Treatment of Uncomplicated Malaria in Western Kenya. J Infect Dis. 2019 May 24;219(12):1969-1979. doi: 10.1093/infdis/jiz027.