A Phase 4 interventional study of Artesunate 2 and Artesunate 4 in Falciparum Malaria, sponsored by University of Oxford. Completed at 19 sites in 10 countries. Open to participants aged 6 Months to 65 Years. Per ClinicalTrials.gov, last updated 2015-06-01.
Sponsored by University of Oxford · Phase 4, Interventional, and Treatment
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 Two different dose regimens of artesunate will be compared at all sites except those in western Cambodia, as unpublished observations from the Thai-Myanmar border suggest the standard lower daily dose of 2mg/kg may enable the earlier detection of low level resistance than a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.
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:
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.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 1,700 is above the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Artesunate 2 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine
Drug: Artesunate 2
Artesunate 4 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine
Drug: Artesunate 4
Artesunate 2 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine
Artesunate 4 mg/kg/day for 3 days followed by a full course of either artemether-lumefantrine or DHA-piperaquine or artesunate-mefloquine or artesunate-amodiaquine
Parasite clearance rate
Defined by the slope of the linear portion of the natural logarithm parasite clearance curve.
Time frame: Day 42
Parasite clearance time
Assessed by microscopy
Time frame: Day 42
Parasite reduction rates and ratios
Assessed by microscopy and quantitative PCR.
Time frame: Day 42
Time for parasite count to fall
Time for parasite count to fall to 50%, 90%, and 99% of initial parasite density
Time frame: 50%, 90%, and 99%
Fever clearance time
The time taken for tympanic temperature to fall below 37˚C and remain there for at least 24 hours
Time frame: > 24 hours
Gametocytemia in patients
Proportion of patients with gametocytemia before, during and after treatment with artesunate, assessed at admission, on days 3, 7 and 14, stratified by presence of gametocytes at enrolment
Time frame: days 0, 3, 7 and 14
Gametocyte carriage rates
Time frame: 14 days
In vitro susceptibility of P.falciparum to artemisinins
Measure the inhibitory concentrations (IC) 50, IC90, IC99 of P. falciparum responses to artemisinins ex vivo
Time frame: Day 42
Pharmacokinetics relationships for artesunate and Dihydroartemisinin (DHA)
Measure half-life, Cmax, AUC, Tmax of artesunate and DHA.
Time frame: Day 42
Parasite molecular markers of drug resistance
To identify the parasite specific molecular marker which is correlated to artemisinin resistance
Time frame: Day 42
Identification of host factors that correlate with slow parasite clearance
To identify host factors influencing the clearance of P. falciparum, e.g. haemoglobinopathies and G6PD deficiency
Time frame: Day 42
Efficacy at D42
The cure rate of artesunate plus ACT treatments at 42 day of follow up.
Time frame: Day 42
Pharmacodynamics relationships for artesunate and Dihydroartemisinin (DHA)
Time frame: Day 42
The record gives a start of May 2011, a primary completion of Apr 2014 and a completion of Dec 2014. It does not say whether these dates are actual or estimated.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2015. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.