Artemisinin Resistance in Bangladesh

This study has been completed.
Sponsor:
Collaborators:
International Centre for Diarrhoeal Disease Research, Bangladesh
World Health Organization
Information provided by (Responsible Party):
Harald Noedl, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00639873
First received: March 14, 2008
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention
Malaria
Drug: Artesunate
Drug: quinine-doxycycline

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

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Cure [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    Cure is defined as adequate clinical and parasitological response (ACPR) as opposed to early treatment failure / late treatment failure


Secondary Outcome Measures:
  • Treatment response [ Time Frame: 42 Days ] [ Designated as safety issue: No ]
    Treatment response parameters: parasite, fever, and gametocyte clearance


Enrollment: 126
Study Start Date: June 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AS 2mg/kg
Artesunate monotherapy 2mg/kg/day for 7 days
Drug: Artesunate
2 or 4 mg/kg/day for 7 days
Other Name: Artesunate
Experimental: AS 4mg/kg
Artesunate monotherapy 4mg/kg/day for 7 days
Drug: Artesunate
2 or 4 mg/kg/day for 7 days
Other Name: Artesunate
Active Comparator: QD Control
Quinine-doxycycline for 7 days
Drug: quinine-doxycycline
quinine-doxycycline for 7 days
Other Name: 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.

  Eligibility

Ages Eligible for Study:   8 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 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
  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: NCT00639873

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

Additional Information:
No publications provided by Medical University of Vienna

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Harald Noedl, Assoc. Prof. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00639873     History of Changes
Other Study ID Numbers: MUW # 83/2008
Study First Received: March 14, 2008
Last Updated: August 22, 2013
Health Authority: Switzerland: Ethikkommission

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

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Doxycycline
Doxycycline hyclate
Quinine
Artemisinins
Artesunate
Artemisinine
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Amebicides

ClinicalTrials.gov processed this record on July 29, 2014