- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00936767
Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia (AMOS)
August 29, 2018 updated by: University of Oxford
Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western
It has now been demonstrated clearly that in Western Cambodia parasitological responses to artesunate and artemether containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world.
Median parasite clearance time (PCT) in patients treated with artesunate 4 mg/kg/day was 78 hours and with 2 mg/kg/day 82 hours, compared to 54 and 48 hours, respectively, in Western Thailand; at 72hours peripheral blood parasitaemia was still detectable in 55% of patients in Western Cambodia, compared to 7.5% in Western Thailand.
Although occasional poor responses to artesunate have been described previously the current reports suggest a consistent problem.
These antimalarials are central to current treatment strategies, and so spread of parasites with reduced artemisinin susceptibility outside this area would be a disaster.
A recent consensus meeting Pnomh Penh agreed that this should indeed be termed resistance, and represented a major threat to malaria control.
Radical containment measures would be needed.
This study aims to address whether a semi-synthetic or fully synthetic peroxide antimalarial would be more effective than artesunate and could therefore be used in Cambodia as part of the elimination strategy.
Artemisone is a semisynthetic derivative of dihydroartemisinin, which importantly changes its tertiary structure.
This drug has also shown promising efficacy for the treatment of uncomplicated falciparum malaria in phase II trials in Thailand and seems to be at least as efficacious as artesunate.
No significant toxicity has been reported for artemisone and it is very well tolerated.
If sensitivity for artemisone has remained intact in Western Cambodia, this will have important implications for the strategies available for containment of the threatening problem of artesunate resistance in Western Cambodia.
It will also have important implications for further development of these drugs for the use in artemisinin combination therapies (ACTs).
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
This is a small detailed randomised open-label clinical trial comparing the efficacy of oral artemisone with oral artesunate in the treatment of uncomplicated falciparum malaria in Western Cambodia.
A detailed pharmacokinetic-pharmacodynamic evaluation and in vitro sensitivity for the study drugs will be part of the assessments.
The overall design and proposed conduct is very similar to the recently completed studies of high dose artesunate.Fever patients in the villages surrounding Pailin (or equivalent study site) in Western Cambodia will be screened with a PfHRP2-based malaria rapid test (Paracheck) by the village malaria workers.
In case of a positive test result, the patient will be transported by the study team to the hospital, full consent (as described above) and enrolment procedures will be conducted.
It will be made clear from the outset that refusal to participate will in no way jeopardize subsequent antimalarial treatment.Eligibility can only be confirmed by a medically qualified investigator.
Subjects who fulfil all the inclusion criteria and have none of the exclusion criteria will be randomised to one of the three treatment arms according to the randomisation schedule.
Subject numbers will be will be assigned when the subject is enrolled after screening and prior to randomisation.Patients will be randomized in blocks of 15 to receive either artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 (N=50) or artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 (N=25.
Study Type
Interventional
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Pailin, Cambodia
- Pailin Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age ≥ 16 years
- Full written informed consent is obtained
- Willingness and ability to comply with the study protocol for the duration of the trial including agreement to 5 days hospitalisation.
- History of fever or presence of fever (tympanic or axillary temperature at >37.5 °C).
- Peripheral blood P.falciparum parasitaemia between 10,000/uL and 200,000/uL. (Mixed malaria infection included)
Exclusion Criteria:
- Known hypersensitivity to the study drugs.
- Any antimalarial drug treatment in the 48 hours prior to enrolment.
- Clinical and/or laboratory features of severe malaria (as defined by WHO).
- Gastrointestinal dysfunction that could alter absorption or motility (i.e. active peptic ulcer, inflammatory bowel disease, malabsorption syndromes, intestinal sub-occlusion or previous major gastrointestinal surgery).
- Presence of intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
- Splenectomy.
- Pregnant or lactating women. Serum test for β-HCG to be performed on any woman of child bearing age unless menstruating.
- Taking any contraindicated medicines (as listed in the most up to date product information)
- Participation in a clinical study within the previous 12 weeks
- Any other condition in the opinion of the investigator makes the patient unsuitable to be a subject
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Artemisone/Mefloquine (AmiM3)
Artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
|
Artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
|
ACTIVE_COMPARATOR: Artesunate/Mefloquine (MAS3)
Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
|
Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment.
Time Frame: 72 hours
|
72 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Parasite clearance times (PCT, slope of the log clearance curve, PRR24, PRR48, PC50, PC90)
Time Frame: Variable
|
Variable
|
Cure rate defined as clearance of asexual parasites without recrudescence within a 28 and 63-day period.
Time Frame: 63 days
|
63 days
|
Number of adverse events
Time Frame: 9 weeks
|
9 weeks
|
Fever clearance time
Time Frame: Variable
|
Variable
|
In-vitro sensitivity to antimalarial drugs of P. falciparum from study patients
Time Frame: Day 0
|
Day 0
|
Molecular determinants of antimalarial drug resistance.
Time Frame: Day 0
|
Day 0
|
Pharmacokinetic parameters
Time Frame: Day 2
|
Day 2
|
Hematocrit levels
Time Frame: Day 63
|
Day 63
|
Gametocyte clearance
Time Frame: Variable
|
Variable
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Duong Socheat, MD, Cambodia National Malaria Control Programme
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (ANTICIPATED)
October 1, 2010
Study Completion (ANTICIPATED)
October 1, 2010
Study Registration Dates
First Submitted
July 9, 2009
First Submitted That Met QC Criteria
July 9, 2009
First Posted (ESTIMATE)
July 10, 2009
Study Record Updates
Last Update Posted (ACTUAL)
August 31, 2018
Last Update Submitted That Met QC Criteria
August 29, 2018
Last Verified
October 1, 2010
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BAKMAL0901
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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