We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia (AMOS)

This study has been withdrawn prior to enrollment.
(Did not get approval)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00936767
First Posted: July 10, 2009
Last Update Posted: October 11, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Mahidol University
Medicines for Malaria Venture
Information provided by:
University of Oxford
  Purpose
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).

Condition Intervention Phase
Uncomplicated Falciparum Malaria Drug: Artemisone/Mefloquine (AmiM3) Drug: Artesunate Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment. [ Time Frame: 72 hours ]

Secondary Outcome Measures:
  • Parasite clearance times (PCT, slope of the log clearance curve, PRR24, PRR48, PC50, PC90) [ Time Frame: Variable ]
  • Cure rate defined as clearance of asexual parasites without recrudescence within a 28 and 63-day period. [ Time Frame: 63 days ]
  • Number of adverse events [ Time Frame: 9 weeks ]
  • Fever clearance time [ Time Frame: Variable ]
  • In-vitro sensitivity to antimalarial drugs of P. falciparum from study patients [ Time Frame: Day 0 ]
  • Molecular determinants of antimalarial drug resistance. [ Time Frame: Day 0 ]
  • Pharmacokinetic parameters [ Time Frame: Day 2 ]
  • Hematocrit levels [ Time Frame: Day 63 ]
  • Gametocyte clearance [ Time Frame: Variable ]

Estimated Enrollment: 75
Study Start Date: October 2010
Estimated Study Completion Date: October 2010
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Artemisone/Mefloquine (AmiM3)
Artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
Other Name: Not available
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
Drug: Artesunate
Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
Other Name: Not available

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00936767


Locations
Cambodia
Pailin Hospital
Pailin, Cambodia
Sponsors and Collaborators
University of Oxford
Mahidol University
Medicines for Malaria Venture
Investigators
Principal Investigator: Duong Socheat, MD Cambodia National Malaria Control Programme
  More Information

Responsible Party: Dr. Arjen Dondorp, University of Oxford
ClinicalTrials.gov Identifier: NCT00936767     History of Changes
Other Study ID Numbers: BAKMAL0901
First Submitted: July 9, 2009
First Posted: July 10, 2009
Last Update Posted: October 11, 2010
Last Verified: October 2010

Keywords provided by University of Oxford:
falciparum malaria
artemisone
artesunate
resistance

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artesunate
Artemisinins
Mefloquine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials