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

Primary Purpose

Vivax Malaria

Status
Completed
Phase
Phase 3
Locations
Thailand
Study Type
Interventional
Intervention
Dihydroartemisinin-Piperaquine
Dihydroartemisinin-Piperaquine
Chloroquine
Chloroquine
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vivax Malaria focused on measuring Vivax, Chloroquine, Primaquine, Dihydroartemisinin-Piperaquine

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shoklo Malaria Research Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

DHA-P 7 days

DHA-P 14 days

Chloroquine 7 days

Chloroquine 14 days

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Adverse Events
Number of adverse events within 28 days of study medication
Recurrence of P. vivax
Recurrence with Plasmodium vivax malaria within 6 months of first treatment dose
Drug concentrations
Chloroquine, piperaquine and primaquine drug levels

Full Information

First Posted
July 11, 2012
Last Updated
April 27, 2016
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT01640574
Brief Title
Comparison Between 7 and 14 Day Primaquine Combined With Dihydroartemisinin-piperaquine or 3 Day Chloroquine Radical Cure of P. Vivax (BPD)
Official Title
Randomised Parallel Open Label Comparison Between 7 and 14 Day Primaquine Combined With 3-day Dihydroartemisinin-piperaquine or 3-day Chloroquine Regimens for Radical Cure of Plasmodium Vivax
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vivax Malaria
Keywords
Vivax, Chloroquine, Primaquine, Dihydroartemisinin-Piperaquine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
680 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DHA-P 7 days
Arm Type
Experimental
Arm Description
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
Arm Title
DHA-P 14 days
Arm Type
Experimental
Arm Description
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
Arm Title
Chloroquine 7 days
Arm Type
Active Comparator
Arm Description
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
Arm Title
Chloroquine 14 days
Arm Type
Active Comparator
Arm Description
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days
Intervention Type
Drug
Intervention Name(s)
Dihydroartemisinin-Piperaquine
Intervention Description
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
Intervention Name(s)
Dihydroartemisinin-Piperaquine
Intervention Description
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
Intervention Name(s)
Chloroquine
Intervention Description
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
Intervention Type
Drug
Intervention Name(s)
Chloroquine
Intervention Description
o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days
Primary Outcome Measure Information:
Title
Recurrence of P. vivax
Description
Recurrence with Plasmodium vivax malaria within 52 weeks of first treatment dose
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Number of adverse events within 28 days of study medication
Time Frame
28 days
Title
Recurrence of P. vivax
Description
Recurrence with Plasmodium vivax malaria within 6 months of first treatment dose
Time Frame
6 months
Title
Drug concentrations
Description
Chloroquine, piperaquine and primaquine drug levels
Time Frame
63 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francois Nosten, MD
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cindy Chu, MD
Organizational Affiliation
Shoklo Malaria Research Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shoklo Malaria Research Unit
City
Mae Sot
State/Province
Tak
ZIP/Postal Code
63110
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
34398667
Citation
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.
Results Reference
derived
PubMed Identifier
30952158
Citation
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.
Results Reference
derived
PubMed Identifier
28170391
Citation
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.
Results Reference
derived

Learn more about this trial

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

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