In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy

Malaria Clinical Trial

Official title:

In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy in Kisumu County, Western Kenya

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01976780
• Other study ID #: WRAIR1935
• Status: Completed
• Phase: Phase 4
• First received: October 25, 2013
• Last updated: May 10, 2017
• Start date: June 2013
• Est. completion date: December 2014

Study information

• Verified date: May 2017
• Source: Global Emerging Infections Surveillance and Response System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Artesunate

• Artemether Lumefantrine

• Mefloquine

Locations

Country	Name	City	State
Kenya	Walter Reed Project, Kombewa Clinic	Kisumu

Sponsors (3)

Lead Sponsor	Collaborator
Global Emerging Infections Surveillance and Response System	United States Army Medical Unit - Kenya, Walter Reed Army Institute of Research (WRAIR)

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Parasite clearance rates and immune response in semi-immune population	To assess the role of pre-existing semi-immunity against malaria in parasite clearance rates and immune response to acute infection	42 days
Other	Production of microbiocidal molecules	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)	42 days
Other	Acute cytokine response	To determine associations between the acute cytokine response with parasitemia clearance rates and immunologic responses	42 days
Primary	Parasitological clearance rates by microscopy	Clearance rates for the first 72 hour period after first ACT dose in patients with uncomplicated P. falciparum malaria	72 hours
Secondary	Parasitological clearance rates by quantitative Polymerase Chain Reaction (PCR)	PCR adjusted clearance rates for the first 72 hours after first ACT dose in patients with uncomplicated P. falciparum malaria	72 hours
Secondary	PCR-adjusted treatment efficacy of AL and AS/MQ		42 days
Secondary	Antimalarial drug sensitivity responses and molecular genotyping	Correlate clinical outcomes with results of above tests	42 days
Secondary	Identify common specific genetic determinants of artemisinin resistance derived from parasite populations		42 days
Secondary	Gametocyte carriage in patients with uncomplicated malaria after treatment		42 days
Secondary	Catalog parasite samples	Correlated to clinical datasets to longitudinally track resistance trends	42 days
Secondary	Pharmacokinetic parameters associated with ACT failure		42 days