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

April 27, 2016 updated by: University of Oxford

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

680

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
    • Tak
      • Mae Sot, Tak, Thailand, 63110
        • Shoklo Malaria Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Drug: 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
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
EXPERIMENTAL: 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
Drug: 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
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
ACTIVE_COMPARATOR: Chloroquine 7 days
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
Drug: Chloroquine
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
Drug: Chloroquine
o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days
ACTIVE_COMPARATOR: Chloroquine 14 days
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days
Drug: Chloroquine
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
Drug: Chloroquine
o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of P. vivax
Time Frame: 52 weeks
Recurrence with Plasmodium vivax malaria within 52 weeks of first treatment dose
52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 28 days
Number of adverse events within 28 days of study medication
28 days
Recurrence of P. vivax
Time Frame: 6 months
Recurrence with Plasmodium vivax malaria within 6 months of first treatment dose
6 months
Drug concentrations
Time Frame: 63 days
Chloroquine, piperaquine and primaquine drug levels
63 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Investigators

  • Principal Investigator: Cindy Chu, MD, Shoklo Malaria Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (ACTUAL)

July 1, 2015

Study Completion (ACTUAL)

December 1, 2015

Study Registration Dates

First Submitted

July 11, 2012

First Submitted That Met QC Criteria

July 11, 2012

First Posted (ESTIMATE)

July 13, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

April 28, 2016

Last Update Submitted That Met QC Criteria

April 27, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SMRU1102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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