Artemisinin Resistance in Cambodia II

NCT00722150 | Completed DMC

• 3 other identifiers: WRAIR 1396HSRRB number A-14479WHO RPC252
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Falciparum Malaria

Keywords

Artesunate; Plasmodium Falciparum; Cambodia

Outcome Measures

Primary Outcomes (2)

• Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR as defined by WHO criteria) on Day 28 and 42

  Day 28 and 42

• Safety and tolerability of oral artesunate

  Up to 42 days

Secondary Outcomes (1)

• Secondary outcome measures are time until parasite, fever, and gametocyte clearance (PCT, FCT, and GCT).

  Day 3

Study Arms (3)

Arm 1

ACTIVE COMPARATOR

Oral Artesunate ("standard" dose)

Drug: Artesunate

Arm 2

ACTIVE COMPARATOR

Oral Artesunate ("ARC1" dose)

Drug: Artesunate

Arm 3

EXPERIMENTAL

Oral Artesunate (experimental "high" dose)

Drug: Artesunate

Interventions

Artesunate DRUG

2 mg/kg/day x 7 days

Arm 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age: 18-65 years old
• 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.
• Written informed consent obtained
• Willing to stay under close medical supervision for the study duration of 42 days
• Otherwise healthy Out-patients

You may not qualify if:

• Mixed malaria infection on admission by malaria smear
• 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
• History of malaria drug therapy administered in the past 30 days
• 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
• 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.
• Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
• 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).
• Unable and/or unlikely to comprehend and/or follow the protocol

Sponsors & Collaborators

• Armed Forces Research Institute of Medical Sciences, Thailand: lead
• World Health Organization: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Tasanh Health Center

Sam Lot District, Battambang, Cambodia

Location

Related Publications (2)

• Bethell D, Se Y, Lon C, Tyner S, Saunders D, Sriwichai S, Darapiseth S, Teja-Isavadharm P, Khemawoot P, Schaecher K, Ruttvisutinunt W, Lin J, Kuntawungin W, Gosi P, Timmermans A, Smith B, Socheat D, Fukuda MM. Artesunate dose escalation for the treatment of uncomplicated malaria in a region of reported artemisinin resistance: a randomized clinical trial. PLoS One. 2011;6(5):e19283. doi: 10.1371/journal.pone.0019283. Epub 2011 May 13.

  PMID: 21603629 DERIVED

• Bethell D, Se Y, Lon C, Socheat D, Saunders D, Teja-Isavadharm P, Khemawoot P, Darapiseth S, Lin J, Sriwichai S, Kuntawungin W, Surasri S, Lee SJ, Sarim S, Tyner S, Smith B, Fukuda MM. Dose-dependent risk of neutropenia after 7-day courses of artesunate monotherapy in Cambodian patients with acute Plasmodium falciparum malaria. Clin Infect Dis. 2010 Dec 15;51(12):e105-14. doi: 10.1086/657402. Epub 2010 Nov 11.

  PMID: 21070142 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artesunate

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Delia Bethell, BM BCh

  Armed Forces Research Institute of Medical Sciences (AFRIMS)

  PRINCIPAL INVESTIGATOR

• Socheat Duong, M.D.

  National Center for Parasitology, Entomology and Malaria Control

  PRINCIPAL INVESTIGATOR

• Se Youry, M.D., M.P.H.M.

  Armed Forces Research Institute of Medical Sciences (AFRIMS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: July 23, 2008
• First Posted: July 25, 2008
• Study Start: July 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: January 25, 2011

Record last verified: 2011-01

Locations

CA (1)