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

NCT01640574 | Completed Phase 3

• 1 other identifier: SMRU1102
• Study Type: interventional
• Target: 680
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Vivax Malaria

Keywords

Vivax; Chloroquine; Primaquine; Dihydroartemisinin-Piperaquine

Outcome Measures

Primary Outcomes (1)

• Recurrence of P. vivax

  Recurrence with Plasmodium vivax malaria within 52 weeks of first treatment dose

  52 weeks

Secondary Outcomes (3)

• Adverse Events

  28 days

• Recurrence of P. vivax

  6 months

• Drug concentrations

  63 days

Study Arms (4)

DHA-P 7 days

EXPERIMENTAL

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

Drug: Dihydroartemisinin-Piperaquine

DHA-P 14 days

EXPERIMENTAL

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

Drug: Dihydroartemisinin-Piperaquine

Chloroquine 7 days

ACTIVE COMPARATOR

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

Drug: Chloroquine

Chloroquine 14 days

ACTIVE COMPARATOR

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

Drug: Chloroquine

Interventions

Dihydroartemisinin-Piperaquine 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 7 days

Chloroquine DRUG

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

Chloroquine 7 days

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Shoklo Malaria Research Unit

Mae Sot, Changwat Tak, 63110, Thailand

Location

Related Publications (4)

• 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.

  PMID: 36534705 DERIVED

• 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.

  PMID: 34398667 DERIVED

• 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.

  PMID: 30952158 DERIVED

• 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.

  PMID: 28170391 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Francois Nosten, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Cindy Chu, MD

  Shoklo Malaria Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2012
• First Posted: July 13, 2012
• Study Start: February 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 28, 2016

Record last verified: 2016-04

Locations

TH (1)