Artemisinin Resistance in Bangladesh

August 22, 2013 updated by: Harald Noedl, Medical University of Vienna
A randomized, controlled clinical trial conducted in Southeastern Bangladesh using artesunate monotherapy to determine the baseline sensitivity of P. falciparum to artemisinins.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

126

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
    • Bandarban
      • Bandarban Sadar, Bandarban, Bangladesh
        • Bandarban Sadar Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cure
Time Frame: 42 days
Cure is defined as adequate clinical and parasitological response (ACPR) as opposed to early treatment failure / late treatment failure
42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment response
Time Frame: 42 Days
Treatment response parameters: parasite, fever, and gametocyte clearance
42 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Collaborators

International Centre for Diarrhoeal Disease Research, Bangladesh
World Health Organization

Investigators

  • Principal Investigator: Harald Noedl, MD, PhD, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

November 1, 2009

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

March 14, 2008

First Submitted That Met QC Criteria

March 14, 2008

First Posted (Estimate)

March 20, 2008

Study Record Updates

Last Update Posted (Estimate)

August 23, 2013

Last Update Submitted That Met QC Criteria

August 22, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MUW # 83/2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Malaria

Clinical Trials on Artesunate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uzbekistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe