Artemisinin Resistance in Bangladesh

NCT ID: NCT00639873

Last Updated: 2013-08-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2009-11-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Malaria

Keywords

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Uncomplicated P. falciparum malaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AS 2mg/kg

Artesunate monotherapy 2mg/kg/day for 7 days

Group Type EXPERIMENTAL

Artesunate

Intervention Type DRUG

2 or 4 mg/kg/day for 7 days

AS 4mg/kg

Artesunate monotherapy 4mg/kg/day for 7 days

Group Type EXPERIMENTAL

Artesunate

Intervention Type DRUG

2 or 4 mg/kg/day for 7 days

QD Control

Quinine-doxycycline for 7 days

Group Type ACTIVE_COMPARATOR

quinine-doxycycline

Intervention Type DRUG

quinine-doxycycline for 7 days

Interventions

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Artesunate

2 or 4 mg/kg/day for 7 days

Intervention Type DRUG

quinine-doxycycline

quinine-doxycycline for 7 days

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role collaborator

World Health Organization

OTHER

Sponsor Role collaborator

Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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Harald Noedl

Assoc. Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Harald Noedl, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

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Bandarban Sadar Hospital

Bandarban Sadar, Bandarban, Bangladesh

Site Status

Countries

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Bangladesh

References

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Starzengruber P, Swoboda P, Fuehrer HP, Khan WA, Hofecker V, Siedl A, Fally M, Graf O, Teja-Isavadharm P, Haque R, Ringwald P, Noedl H. Current status of artemisinin-resistant falciparum malaria in South Asia: a randomized controlled artesunate monotherapy trial in Bangladesh. PLoS One. 2012;7(12):e52236. doi: 10.1371/journal.pone.0052236. Epub 2012 Dec 18.

Reference Type DERIVED
PMID: 23272227 (View on PubMed)

Related Links

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http://www.marib.org

MARIB - Malaria Research Initiative Bandarban

http://www.meduniwien.ac.at

Medical University of Vienna

Other Identifiers

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MUW # 83/2008

Identifier Type: -

Identifier Source: org_study_id