Study on the Treatment of Vivax Malaria

NCT ID: NCT01074905

Last Updated: 2013-08-28

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

PHASE3

Total Enrollment

655 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2012-10-31

Brief Summary

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This is a randomised open label trial with follow up for 1 year. 660 adults and children above 6 months diagnosed with acute Plasmodium vivax will be randomised into 3 groups, either chloroquine, artesunate, or chloroquine/primaquine therapy. Participants will be screened on the day of inclusion then followed weekly for 8 visits and every 4 weeks until week 52. The primary objective of the study is to compare the efficacy of the WHO and Thai Ministry of Public Health recommended radical curative regimen of chloroquine and primaquine with the currently used monotherapy regimens of chloroquine and artesunate along the Thai-Burmese border.

Detailed Description

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Considerably less attention has been paid to Plasmodium vivax epidemiology than Plasmodium falciparum. In areas of relatively low unstable transmission, which comprise the majority of P.vivax affected areas, vivax malaria is predominantly a disease of children (Luxemburger et al 1999). Chloroquine has long been the standard treatment for vivax malaria. Primaquine is recommended for radical cure of vivax malaria, but is difficult to administer due to dosing duration and side effects.

This study aims to characterize the epidemiologic history comparing the efficacy of 3 antimalarial regimens (chloroquine, artesunate, and chloroquine/primaquine) for plasmodium vivax in western Thailand. Chloroquine is currently the standard of treatment for Plasmodium vivax. Due to the long half-life or chloroquine, the first relapse of vivax malaria may be delayed. In contrast, artesunate has a very short half-life, thus, having no impact on first relapse. It is not known whether chloroquine reduces the overall number of relapses, or only delays the first relapse. There are many important questions about the biology of vivax malaria of relevance to treatment that remain unanswered. For example is the number of relapses per infection (i.e. per successful inoculation) predetermined or adaptive? If it is predetermined then suppression of the first relapse (as with chloroquine, mefloquine or piperaquine) will reduce the total number of relapses and this is a clear benefit. If it is adaptive then these drugs will simply delay the relapses and there is less clear benefit. These various uncertainties illustrate the importance of detailed comparative longitudinal evaluations. In order to characterize the biology of vivax malaria, it will be necessary to compare regimens with and without primaquine. Because of the challenges that face primaquine prescription (side effects, toxicity in G6PD deficient patients and duration of treatment), it is not commonly deployed along the Thai Burma border. In effect, we will be comparing usual practice (non primaquine regimens) with the recommended WHO and Thai MOPH practice (use of primaquine for 14 days). The information we will gather is crucial to the understanding of chloroquine and its effect on the vivax parasite. This will lead to future studies and invariably change the way we treat vivax malaria.

Conditions

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Vivax Malaria

Keywords

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vivax malaria artesunate chloroquine primaquine relapse

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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Artesunate

2 mg/kg/day as single daily dose given for 5 days; maximum dose range is 1.6 to 2.4 mg/kg/day or a total of 8 to 12 mg/kg.

Group Type ACTIVE_COMPARATOR

Artesunate

Intervention Type DRUG

2 mg/kg/day as single daily dose given for 5 days; maximum dose range is 1.6 to 2.4 mg/kg/day or a total of 8 to 12 mg/kg.

Chloroquine

25 mg base/kg given in divided doses (10,10,5) over 3 days; Absolute range 20-30 mg/kg.

Group Type ACTIVE_COMPARATOR

Chloroquine

Intervention Type DRUG

25 mg base/kg given in divided doses (10,10,5) over 3 days; Absolute range 20-30 mg/kg.

Chloroquine/Primaquine

Chloroquine 3 days and Primaquine 14 days

Group Type EXPERIMENTAL

Chloroquine/Primaquine

Intervention Type DRUG

Chloroquine 3 days and Primaquine 14 days

Interventions

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Artesunate

2 mg/kg/day as single daily dose given for 5 days; maximum dose range is 1.6 to 2.4 mg/kg/day or a total of 8 to 12 mg/kg.

Intervention Type DRUG

Chloroquine

25 mg base/kg given in divided doses (10,10,5) over 3 days; Absolute range 20-30 mg/kg.

Intervention Type DRUG

Chloroquine/Primaquine

Chloroquine 3 days and Primaquine 14 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Adults and children \> 6 months
* Weight \> 7 kg for children
* Have not had primaquine since last Pv episode
* Participant (or parent/guardian if \< 18 years old) is willing and able to give written informed consent
* Microscopic diagnosis of Plasmodium vivax mono-infection
* Ability (in the investigators opinion) and willingness of patient or parent/guardian to comply with all study requirements

Exclusion Criteria

* Allergy to artesunate, chloroquine or primaquine
* Severe malaria
* Patients with microscopic diagnosis of co-infection with Plasmodium falciparum
* Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study
* Inability to tolerate oral medication
* Pregnancy
* Blood transfusion in the last 3 months
* Antimalarial in last 2 months
Minimum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mahidol University

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Francois Nosten, MD

Role: PRINCIPAL_INVESTIGATOR

Shoklo Malaria Research Unit

Locations

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Shoklo Malaria Research Unit

Mae Sot, , Thailand

Site Status

Countries

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Thailand

References

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Stadler E, Cromer D, Mehra S, Adekunle AI, Flegg JA, Anstey NM, Watson JA, Chu CS, Mueller I, Robinson LJ, Schlub TE, Davenport MP, Khoury DS. Population heterogeneity in Plasmodium vivax relapse risk. PLoS Negl Trop Dis. 2022 Dec 19;16(12):e0010990. doi: 10.1371/journal.pntd.0010990. eCollection 2022 Dec.

Reference Type DERIVED
PMID: 36534705 (View on PubMed)

Chu CS, Phyo AP, Lwin KM, Win HH, San T, Aung AA, Raksapraidee R, Carrara VI, Bancone G, Watson J, Moore KA, Wiladphaingern J, Proux S, Sriprawat K, Winterberg M, Cheah PY, Chue AL, Tarning J, Imwong M, Nosten F, White NJ. Comparison of the Cumulative Efficacy and Safety of Chloroquine, Artesunate, and Chloroquine-Primaquine in Plasmodium vivax Malaria. Clin Infect Dis. 2018 Oct 30;67(10):1543-1549. doi: 10.1093/cid/ciy319.

Reference Type DERIVED
PMID: 29889239 (View on PubMed)

Pratt B, Zion D, Lwin KM, Cheah PY, Nosten F, Loff B. Closing the translation gap for justice requirements in international research. J Med Ethics. 2012 Sep;38(9):552-8. doi: 10.1136/medethics-2011-100301. Epub 2012 Mar 16.

Reference Type DERIVED
PMID: 22427705 (View on PubMed)

Other Identifiers

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SMRU0908

Identifier Type: -

Identifier Source: org_study_id