In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: AS/MQ 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. |
Drug: Artesunate
Other Names:
Drug: Mefloquine
Other Names:
|
| Active Comparator: AL 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. |
Drug: Artemether Lumefantrine
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Parasitological clearance rates by microscopy [72 hours]
Clearance rates for the first 72 hour period after first ACT dose in patients with uncomplicated P. falciparum malaria
Secondary Outcome Measures
- Parasitological clearance rates by quantitative Polymerase Chain Reaction (PCR) [72 hours]
PCR adjusted clearance rates for the first 72 hours after first ACT dose in patients with uncomplicated P. falciparum malaria
- PCR-adjusted treatment efficacy of AL and AS/MQ [42 days]
- Antimalarial drug sensitivity responses and molecular genotyping [42 days]
Correlate clinical outcomes with results of above tests
- Identify common specific genetic determinants of artemisinin resistance derived from parasite populations [42 days]
- Gametocyte carriage in patients with uncomplicated malaria after treatment [42 days]
- Catalog parasite samples [42 days]
Correlated to clinical datasets to longitudinally track resistance trends
- Pharmacokinetic parameters associated with ACT failure [42 days]
Other Outcome Measures
- Parasite clearance rates and immune response in semi-immune population [42 days]
To assess the role of pre-existing semi-immunity against malaria in parasite clearance rates and immune response to acute infection
- Production of microbiocidal molecules [42 days]
To determine if stimulation of Peripheral Blood Mononuclear Cells (PBMC) (with MSP-1 or CSP antigens) elicit production of microbiocidal molecules (to be pursued only in if pre-existing immunity is shown to affect rate of clearance)
- Acute cytokine response [42 days]
To determine associations between the acute cytokine response with parasitemia clearance rates and immunologic responses
Eligibility Criteria
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:
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Walter Reed Project, Kombewa Clinic | Kisumu | Kenya |
Sponsors and Collaborators
- Global Emerging Infections Surveillance and Response System
- United States Army Medical Unit - Kenya
- Walter Reed Army Institute of Research (WRAIR)
Investigators
- Study Chair: James F Cummings, MD, GEIS
- Principal Investigator: Ben Andagalu, MD, Kenya Medical Research Institute/Walter Reed Project
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WRAIR1935