Artemisinin Resistance in Bangladesh

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. Identifier: NCT00639873
Recruitment Status : Completed
First Posted : March 20, 2008
Last Update Posted : August 23, 2013
International Centre for Diarrhoeal Disease Research, Bangladesh
World Health Organization
Information provided by (Responsible Party):
Harald Noedl, Medical University of Vienna

Brief Summary:
A randomized, controlled clinical trial conducted in Southeastern Bangladesh using artesunate monotherapy to determine the baseline sensitivity of P. falciparum to artemisinins.

Condition or disease Intervention/treatment
Malaria Drug: Artesunate Drug: quinine-doxycycline

Detailed Description:

A total number of 100 volunteers with acute uncomplicated falciparum malaria will be randomly assigned one of 3 arms to be treated with artesunate monotherapy or quinine/doxycycline for 7 days at a ratio of 2:2:1. 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). Study participants will be otherwise healthy malaria patients aged 8 to 65 years with uncomplicated falciparum malaria recruited at the Bandarban Sadar Hospital, Bangladesh.

The artesunate will be administered orally (a single dose of 2 or 4 mg/kg/day) over a total duration of 7 days by directly observed therapy.

Patients will be admitted to the hospital for the duration of study drug administration or until all signs and symptoms of malaria have disappeared, whichever comes later. Thereafter they will be followed as outpatients until Day 42 with scheduled follow-up visits on Day 14, 28, 35, and 42.

In vitro drug sensitivity assays will be performed from samples on inclusion and in case of recrudescence. Drug levels will be measured on the first and last day of therapy.

Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR) on Day 28 and 42. Secondary outcome measures are time until parasite, fever, and gametocyte clearance (PCT, FCT, and GCT). Parasite genotyping will be used to distinguish recrudescences from reinfections by PCR for patients in whom recrudescences cannot be fully excluded. Subjects will be monitored for clinical adverse events throughout the study duration.

Blood will be drawn on the day of admission (before initiating therapy) for in vitro drug sensitivity testing and for PCR (markers of drug resistance and to distinguish recrudescence from reinfection by genotyping). Malaria smears will be prepared twice daily until parasite clearance and on Days 7, 14, 21, 28, 35, and 42 or whenever symptoms consistent with malaria appear. Plasma samples for determining drug levels will be obtained on the first and last day of therapy. Study participation for each individual will be 42 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Artemisinin Resistance in Bangladesh
Study Start Date : June 2008
Primary Completion Date : November 2009
Study Completion Date : November 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria
U.S. FDA Resources

Arm Intervention/treatment
Experimental: AS 2mg/kg
Artesunate monotherapy 2mg/kg/day for 7 days
Drug: Artesunate
2 or 4 mg/kg/day for 7 days
Experimental: AS 4mg/kg
Artesunate monotherapy 4mg/kg/day for 7 days
Drug: Artesunate
2 or 4 mg/kg/day for 7 days
Active Comparator: QD Control
Quinine-doxycycline for 7 days
Drug: quinine-doxycycline
quinine-doxycycline for 7 days

Primary Outcome Measures :
  1. Cure [ Time Frame: 42 days ]
    Cure is defined as adequate clinical and parasitological response (ACPR) as opposed to early treatment failure / late treatment failure

Secondary Outcome Measures :
  1. Treatment response [ Time Frame: 42 Days ]
    Treatment response parameters: parasite, fever, and gametocyte clearance

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:   8 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Acute symptomatic falciparum malaria infection as determined by malaria smear with a parasite density of 1,000 to 100,000 asexual parasites/uL as determined on the screening smear with fever (defined as ≥37.5C), or reported history of fever within the last 48 hours.
  2. Age: 8-65 years old
  3. All females between the age of 12 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 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 outpatients

Exclusion Criteria:

  1. Pregnant women, nursing mothers, or women of childbearing potential who do not use an acceptable method of contraception
  2. Mixed malaria infection on admission by malaria smear
  3. A previous history of intolerance or hypersensitivity to the study drugs or to drugs with similar chemical structures
  4. Malaria drug therapy administered in the past 30 days by history
  5. 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.
  6. Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
  7. Signs or symptoms of severe malaria (as defined by WHO 2000)
  8. Unable and/or unlikely to comprehend and/or follow the protocol

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 identifier (NCT number): NCT00639873

Bandarban Sadar Hospital
Bandarban Sadar, Bandarban, Bangladesh
Sponsors and Collaborators
Medical University of Vienna
International Centre for Diarrhoeal Disease Research, Bangladesh
World Health Organization
Principal Investigator: Harald Noedl, MD, PhD Medical University of Vienna

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Harald Noedl, Assoc. Prof. Dr., Medical University of Vienna Identifier: NCT00639873     History of Changes
Other Study ID Numbers: MUW # 83/2008
First Posted: March 20, 2008    Key Record Dates
Last Update Posted: August 23, 2013
Last Verified: August 2013

Keywords provided by Harald Noedl, Medical University of Vienna:
Uncomplicated P. falciparum malaria

Additional relevant MeSH terms:
Protozoan Infections
Parasitic Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Analgesics, Non-Narcotic
Sensory System Agents