Comparison Between 7 and 14 Day Primaquine Combined With Dihydroartemisinin-piperaquine or 3 Day Chloroquine Radical Cure of P. Vivax (BPD)

NCT ID: NCT01640574

Last Updated: 2016-04-28

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

680 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2015-12-31

Brief Summary

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In Southeast Asia, Plasmodium vivax (Pv) infection reaches 50-80% and bears a greater burden of disease than Plasmodium falciparum (Pf). As control over Pf improves, Pv will assume increasingly larger percentages of malaria prevalence. The chronicity of Pv, due to the latent liver stage (hypnozoite) not eradicated by chloroquine, causes recurring disability and compounds the economic burden of those with symptomatic disease. The only widely available treatment for hypnozoites is primaquine, which, because of challenges with tolerability, safety in G6PD deficient persons, and compliance, is not commonly prescribed for the treatment of Pv. Currently, chloroquine is used for the treatment of the blood stages of Pv, however, there are concerns about increasing parasite resistance. Alternative treatments, such as artesunate, should be considered in the future of the treatment of blood stage Pv. The use of primaquine in the treatment of hypnozoites (radical cure) should be emphasized so that transmission of Pv can be controlled.

This study aims to determine the optimal primaquine regimen for radical cure of Plasmodium vivax. Chloroquine is currently the standard of treatment for Plasmodium vivax. Chloroquine may have synergistic effects when used with primaquine and due to its long half-life may delay the first relapse of vivax malaria. In contrast, artesunate does not have documented interactions with primaquine and has a very short half-life, thus, presumably will have no impact on first relapse. Combining primaquine with these two anti-malarials may lead to an alternative regimen for Pv infection and changing the primaquine dosing regimen may lead to a more practical and efficacious therapy.

Detailed Description

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Conditions

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Vivax 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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DHA-P 7 days

Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days

Group Type EXPERIMENTAL

Dihydroartemisinin-Piperaquine

Intervention Type DRUG

Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days

DHA-P 14 days

Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days

Group Type EXPERIMENTAL

Dihydroartemisinin-Piperaquine

Intervention Type DRUG

Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days

Chloroquine 7 days

Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days

Group Type ACTIVE_COMPARATOR

Chloroquine

Intervention Type DRUG

Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days

Chloroquine 14 days

Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days

Group Type ACTIVE_COMPARATOR

Chloroquine

Intervention Type DRUG

o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days

Interventions

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Dihydroartemisinin-Piperaquine

Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days

Intervention Type DRUG

Dihydroartemisinin-Piperaquine

Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days

Intervention Type DRUG

Chloroquine

Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days

Intervention Type DRUG

Chloroquine

o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* ≥ 6 months old
* Microscopic diagnosis of Plasmodium vivax malaria mono-infection
* Participant or parent/guardian is willing and able to give informed consent for participation in the study
* Able (in the Investigators opinion) and willing to comply with all study requirements.

Exclusion Criteria

* Severe malaria
* History of allergy or adverse reaction to artesunate, piperaquine, chloroquine, or primaquine
* Blood transfusion in the past 3 months
* G6PD deficiency by rapid test
* Hematocrit ≤ 25%
* Pregnancy at the time of screening
* Breastfeeding an infant \< 6 months old
* 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
Minimum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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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

University of Oxford

Cindy Chu, MD

Role: PRINCIPAL_INVESTIGATOR

Shoklo Malaria Research Unit

Locations

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Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, 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, Watson JA, Phyo AP, Win HH, Yotyingaphiram W, Thinraow S, Soe NL, Aung AA, Wilaisrisak P, Kraft K, Imwong M, Hanpithakpong W, Blessborn D, Tarning J, Proux S, Ling C, Nosten FH, White NJ. Determinants of Primaquine and Carboxyprimaquine Exposures in Children and Adults with Plasmodium vivax Malaria. Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0130221. doi: 10.1128/AAC.01302-21. Epub 2021 Aug 16.

Reference Type DERIVED
PMID: 34398667 (View on PubMed)

Chu CS, Phyo AP, Turner C, Win HH, Poe NP, Yotyingaphiram W, Thinraow S, Wilairisak P, Raksapraidee R, Carrara VI, Paw MK, Wiladphaingern J, Proux S, Bancone G, Sriprawat K, Lee SJ, Jeeyapant A, Watson J, Tarning J, Imwong M, Nosten F, White NJ. Chloroquine Versus Dihydroartemisinin-Piperaquine With Standard High-dose Primaquine Given Either for 7 Days or 14 Days in Plasmodium vivax Malaria. Clin Infect Dis. 2019 Apr 8;68(8):1311-1319. doi: 10.1093/cid/ciy735.

Reference Type DERIVED
PMID: 30952158 (View on PubMed)

Chu CS, Bancone G, Moore KA, Win HH, Thitipanawan N, Po C, Chowwiwat N, Raksapraidee R, Wilairisak P, Phyo AP, Keereecharoen L, Proux S, Charunwatthana P, Nosten F, White NJ. Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens. PLoS Med. 2017 Feb 7;14(2):e1002224. doi: 10.1371/journal.pmed.1002224. eCollection 2017 Feb.

Reference Type DERIVED
PMID: 28170391 (View on PubMed)

Other Identifiers

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SMRU1102

Identifier Type: -

Identifier Source: org_study_id

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