Artemisinin Resistance in Cambodia II (ARC II)

This study has been completed.
Sponsor:
Collaborators:
World Health Organization
Bill and Melinda Gates Foundation
Information provided by:
Armed Forces Research Institute of Medical Sciences, Thailand
ClinicalTrials.gov Identifier:
NCT00722150
First received: July 23, 2008
Last updated: January 24, 2011
Last verified: January 2011
  Purpose

The purpose of this study is to determine the impact of varying doses of artesunate on treatment outcome and whether higher doses of artesunate can overcome the problem of compromised artemisinin sensitivity in the region.

To determine the safety and tolerability of this previously untested experimental high dose (6 mg/Kg/D X 7 day, total 42 mg/Kg) artesunate monotherapy regimen.


Condition Intervention
Falciparum Malaria
Drug: Artesunate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Artemisinin Resistance in Cambodia II

Resource links provided by NLM:


Further study details as provided by Armed Forces Research Institute of Medical Sciences, Thailand:

Primary Outcome Measures:
  • Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR as defined by WHO criteria) on Day 28 and 42 [ Time Frame: Day 28 and 42 ] [ Designated as safety issue: No ]
  • Safety and tolerability of oral artesunate [ Time Frame: Up to 42 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary outcome measures are time until parasite, fever, and gametocyte clearance (PCT, FCT, and GCT). [ Time Frame: Day 3 ] [ Designated as safety issue: No ]

Enrollment: 143
Study Start Date: July 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
Oral Artesunate ("standard" dose)
Drug: Artesunate
2 mg/kg/day x 7 days
Active Comparator: Arm 2
Oral Artesunate ("ARC1" dose)
Drug: Artesunate
4 mg/kg/day x 7 days
Experimental: Arm 3
Oral Artesunate (experimental "high" dose)
Drug: Artesunate
6 mg/kg/day x 7 days

Detailed Description:

A total of 150 volunteers with acute uncomplicated falciparum malaria will be randomly assigned one of 3 arms to be treated with artesunate monotherapy for 7 days at a ratio of 2:1:2.

Arm 2 serves as a control and will serve as a bridge to the ARC 1 study performed in 2006/2007. Patients in Arm 1 will receive a relatively low "standard" dose, and patients in Arm 2 will receive the intermediate dose of 4 mg/kg that was used in the ARC1 study. Patients in Arm 3 will receive an experimental "high-dose" regimen. Currently available safety data extends to subjects who have received the 28 mg/Kg total dose over 7 days and to another study administering 8 mg/Kg/day for 3 days (total dose 24 mg/Kg). Subjects randomized into this study's 'high-dose' Arm 3 will, therefore, receive a total dose that is higher than has been previously studied in humans.

The study design will be based on the WHO recommendations for the 'Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria' (WHO, 2003).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute symptomatic falciparum malaria infection as determined by malaria smear with a parasite density of 1000 to 200,000 asexual parasites/Micro-liter as determined on the thick/thin screening smear with fever (defined as ≥ 37.5ºC), or reported history of fever within the last 48 hours.
  2. Age: 18-65 years old
  3. All females between the age of 18 and 50 are required to have a negative human chorionic gonadotropin (hCG) pregnancy test (urine). All females of childbearing potential (not surgically sterile, or less than two years menopausal) are required to use an acceptable method of contraception, such as implant, injectable, or oral contraceptive(s), if possible with additional barrier contraception, intrauterine device, sexual abstinence, or vasectomized partner, throughout the study.
  4. Written informed consent obtained
  5. Willing to stay under close medical supervision for the study duration of 42 days
  6. Otherwise healthy Out-patients

Exclusion Criteria:

  1. Pregnant women, nursing mothers, or women of childbearing potential who do not use an acceptable method of contraception (as described in Inclusion Criteria, # 3)
  2. Mixed malaria infection on admission by malaria smear
  3. A previous history of intolerance or hypersensitivity to the study drug artesunate or to drugs with similar chemical structures, such as artemether, artemisinin or dihydroartemisinin
  4. History of malaria drug therapy administered in the past 30 days
  5. Previous participation in this trial, or participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study
  6. History of significant cardiovascular, liver or renal functional abnormality or any other clinically significant illness, which in the opinion of the investigator would place them at increased risk.
  7. Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
  8. Signs or symptoms of severe malaria (adapted from WHO recommendations (2003): prostration, impaired consciousness, respiratory distress, convulsions, systolic blood pressure < 70 mm Hg, abnormal bleeding, severe anemia with hemoglobin < 8 g/dL or HCT < 24%, hyperparasitemia at > 4% parasitized red blood cells).
  9. Unable and/or unlikely to comprehend and/or follow the protocol
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00722150

Locations
Cambodia
Tasanh Health Center
Sam Lot District, Battambang, Cambodia
Sponsors and Collaborators
Armed Forces Research Institute of Medical Sciences, Thailand
World Health Organization
Bill and Melinda Gates Foundation
Investigators
Principal Investigator: Delia Bethell, BM BCh Armed Forces Research Institute of Medical Sciences (AFRIMS)
Principal Investigator: Socheat Duong, M.D. NCHADS - Ministry of Health of Cambodia
Principal Investigator: Se Youry, M.D., M.P.H.M. Armed Forces Research Institute of Medical Sciences (AFRIMS)
  More Information

No publications provided by Armed Forces Research Institute of Medical Sciences, Thailand

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mark Fukuda, M.D., LTC, MC, Armed Forces Research Institute of Medical Sciences (AFRIMS)
ClinicalTrials.gov Identifier: NCT00722150     History of Changes
Other Study ID Numbers: WRAIR 1396, HSRRB number A-14479, WHO RPC252
Study First Received: July 23, 2008
Last Updated: January 24, 2011
Health Authority: United States: Federal Government

Keywords provided by Armed Forces Research Institute of Medical Sciences, Thailand:
Artesunate
Plasmodium Falciparum
Cambodia

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artemisinins
Artesunate
Artemisinine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Amebicides

ClinicalTrials.gov processed this record on July 28, 2014