In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy

NCT ID: NCT01976780

Last Updated: 2017-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2014-12-31

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.

Conditions

Malaria

Study Design

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

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Artesunate

Intervention Type: DRUG

Mefloquine

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Artemether Lumefantrine

Intervention Type: DRUG

Interventions

Artesunate

Intervention Type: DRUG

Artemether Lumefantrine

Intervention Type: DRUG

Mefloquine

Intervention Type: DRUG

Other Intervention Names

AS; AL; MQ

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Army Medical Unit - Kenya

FED

Sponsor Role: collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

Global Emerging Infections Surveillance and Response System

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James F Cummings, MD

Role: STUDY_CHAIR

GEIS

Ben Andagalu, MD

Role: PRINCIPAL_INVESTIGATOR

Kenya Medical Research Institute/Walter Reed Project

Locations

Walter Reed Project, Kombewa Clinic

Kisumu, , Kenya

Countries

Kenya

References

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.

Reference Type: DERIVED

PMID: 30649381 (View on PubMed)

Other Identifiers

WRAIR1935

Identifier Type: -

Identifier Source: org_study_id