Overview

Tracking Resistance to Artemisinin (TRAC)

Status:
Completed

Trial end date:
2014-12-01

Target enrollment:
0

Participant gender:
All

Summary

Because the artemisinins are the most potent antimalarial drugs, the reduction in parasite numbers is rapid. Therefore, early measures of reducing parasite counts are needed. This study will look at conventional markers of parasite reduction e.g. parasite clearance time, parasite reduction ratio, and the time to achieve a fall of 50%, 90% and 99% of the pre-treatment parasitaemia. Defining artemisinin resistance requires the use of artesunate (AS) alone because it is now appreciated that the partner drug in a combination treatment has a significant impact on the rate of parasite clearance. This study will dose patients for 3 days with AS alone (or longer until parasites clear) and measure the parasite count frequently in order to be able to define an accurate regression line of a graph of the natural logarithm of the parasite count (Y axis) versus time (X axis). This will be followed by a full course of an artemisinin combination therapy (ACT). Two different dose regimens of artesunate will be compared at all sites except those in western Cambodia, as unpublished observations from the Thai-Myanmar border suggest the standard lower daily dose of 2mg/kg may enable the earlier detection of low level resistance than a 4mg/kg daily dose.

Phase:

Phase 4

Accepts Healthy Volunteers?

Details

Lead Sponsor:

University of Oxford

Collaborators:

Mahidol University
Worldwide Antimalarial Resistance Network

Treatments:

Amodiaquine
Artemether
Artemether-lumefantrine combination
Artemisinins
Artesunate
Lumefantrine
Mefloquine
Piperaquine

Criteria

Inclusion Criteria:

- Male or female, aged from 6 months to 65 years old, inclusive

- Acute uncomplicated P. falciparum malaria, confirmed by positive blood smear with
asexual forms of P. falciparum (or mixed with non-falciparum species)

- Asexual P. falciparum parasitaemia: 10,000 to 200,000/uL, determined on a thin or
thick blood film

- Fever defined as > 37.5°C tympanic temperature or a history of fever within the last
24 hours

- Written informed consent (by legally acceptable representative in case of children)

- Willingness and ability of the patients/guardians to comply with the study protocol
for the duration of the study

Exclusion Criteria:

- Signs of severe/complicated malaria (WHO, 2000)

- Haematocrit < 25% or haemoglobin (Hb) < 8 g/dL at enrollment

- Acute illness other than malaria requiring treatment

- For females: pregnancy, breast feeding

- Patients who have received artemisinin or a derivative or an artemisinin-containing
combination therapy (ACT) within the previous 7 days

- History of allergy or known contraindication to artemisinins, or to the ACT to be used
at the site

- Previous splenectomy