Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia
Information source: University of Oxford
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Uncomplicated Falciparum Malaria
Intervention: Artemisone/Mefloquine (AmiM3) (Drug); Artesunate (Drug)
Phase: Phase 2/Phase 3
Status: Withdrawn
Sponsored by: University of Oxford Official(s) and/or principal investigator(s): Duong Socheat, MD, Principal Investigator, Affiliation: Cambodia National Malaria Control Programme
Summary
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).
Clinical Details
Official title: Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment.
Secondary outcome: Parasite clearance times (PCT, slope of the log clearance curve, PRR24, PRR48, PC50, PC90)Cure rate defined as clearance of asexual parasites without recrudescence within a 28 and 63-day period. Number of adverse events Fever clearance time In-vitro sensitivity to antimalarial drugs of P. falciparum from study patients Molecular determinants of antimalarial drug resistance. Pharmacokinetic parameters Hematocrit levels Gametocyte clearance
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.
Eligibility
Minimum age: 16 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Pailin Hospital, Pailin, Cambodia
Additional Information
Starting date: October 2010
Last updated: October 8, 2010
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