Clinical Trials Logo

Clinical Trial 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 Two different dose regimens of artesunate will be compared at all sites except those in western Cambodia, as unpublished observations from the Thai-Myanmar border suggest the standard lower daily dose of 2mg/kg may enable the earlier detection of low level resistance than a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.


Clinical Trial Description

Background:

Artemisinins are the cornerstone of current antimalarial treatment. Evidence of reduced susceptibility to artemisinins in Western Cambodia was first presented in January 2007 and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study conducted by our group. Artemisinin resistance was manifest by a marked slowing of parasite clearance. The spread of highly artemisinin resistant falciparum malaria would have devastating consequences for malaria control and elimination. The response to artemisinin resistance in P. falciparum depends critically upon answering one pivotal question: how far has it spread? This research proposal focuses on filling critical gaps in knowledge that are essential to planning an effective response.

Objectives/Hypothesis/Questions:

This is a multi-centre study with the primary objective of comparing the P. falciparum parasite clearance compared to a reference parasite clearance rate obtained from historical data in artemisinin sensitive falciparum malaria.

The aim of this large scale study is to determine if artemisinin resistance has spread and if so, how far it has spread.

Research design:

This is a multi-centre, open-label randomised trial to assess the clearance rates of peripheral blood P. falciparum parasitaemias in patients with acute uncomplicated falciparum malaria treated with two different doses of artesunate.

The study will recruit patients with acute uncomplicated P. falciparum malaria. The total number of patients for this study is expected to be 1800.

Patients will be randomised 1:1 to receive either:

- AS2: Artesunate 2 mg/kg/day for 3 days OR

- AS4: Artesunate 4 mg/kg/day for 3 days

- followed by a full course of Artesunate- mefloquine (MAS3) Patients will be hospitalised for at least the 1st three days. During hospitalisation, patients will have malaria parasite count done at 0, 4, 6, 8, 12, then every 6 hours until parasite clearance. The weekly follow up is until day 14 (on Day 7 and Day 14).

Value and significance of the research The study aims to address a simple but crucial question regarding artemisinin resistance for which currently there is no answer: has artemisinin resistant Plasmodium falciparum spread from Western Cambodia? The results will determine how to approach the subsequent efforts; strengthening of strategies for eliminating the resistant parasites in Western Cambodia if the resistance is confined to this area, or for containment and malaria control if the resistant parasites have already spread.

Potential outcomes Within one year we expect to produce a map of the geographical extent, prevalence and severity of artemisinin resistance. ;


Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT01350856
Study type Interventional
Source University of Oxford
Contact
Status Completed
Phase Phase 4
Start date May 2011
Completion date December 2014

See also
  Status Clinical Trial Phase
Completed NCT00440752 - The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance N/A
Completed NCT01144702 - Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Malaria by Plasmodium Falciparum Phase 2/Phase 3
Terminated NCT00400101 - Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Peptides Phase 1
Completed NCT00859807 - A Bioequivalence Study Comparing Camoquin® Suspension (Pfizer) To Flavoquine® Tablets (Sanofi Aventis) In Healthy Subjects Phase 4
Completed NCT04222088 - TES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014
Completed NCT01115439 - Artesunate+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria N/A
Completed NCT00282919 - A Three Day Trial of Azithromycin Plus Chloroquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria Phase 2
Completed NCT04422015 - Biological Mechanisms in Afebrile P. Falciparum Malaria
Completed NCT00894660 - A Bioequivalence Study Comparing Amodiaquine Tablet (Pfizer) To Amodiaquine Tablets (Arsuamoon-Guilin China) In Healthy Subjects Phase 1
Completed NCT00894374 - Bioequivalence Study Comparing Artesunate Tablet To Arsuamoon® Tablets (Guilin-China) In Healthy Subjects Phase 1
Completed NCT00493363 - Clinical Investigation of In-vivo Susceptibility of P.Falciparum to Artesunate in Western Cambodia N/A
Completed NCT00158548 - ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan Phase 3
Withdrawn NCT04289558 - Nitrite Infusion in Children With Malaria Phase 1
Completed NCT01374126 - Azithromycin Combination Therapy for the Treatment of Severe Malaria Phase 2
Completed NCT00722150 - Artemisinin Resistance in Cambodia II N/A
Completed NCT00157833 - A Randomized Trial of Coartemether and Artekin for the Treatment of Uncomplicated Malaria in Papua, Indonesia. N/A
Completed NCT00513669 - Phase Ib Trial of Two Virosome Formulated Malaria Vaccine Components (PEV 301, PEV 302) in Tanzania Phase 1
Completed NCT00442377 - Study to Investigate the Induction of an Protective Immune Response to Malaria N/A
Completed NCT00403260 - Pyronaridine - Artesunate (3:1) Versus Mefloquine Plus Artesunate in Plasmodium Falciparum Malaria Patients Phase 3
Completed NCT01365598 - Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda Phase 3