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

Phase 3

Completed

• Conditions: Vivax Malaria
• Interventions: Drug: Dihydroartemisinin-Piperaquine; Drug: Chloroquine

• Registration Number: NCT01640574
• Lead Sponsor: University of Oxford

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-07-11
• Study First Submitted QC: 2012-07-11
• Study First Posted: 2012-07-13
• Primary Completion: 2015-07
• Study Completion: 2015-12
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-27
• Last Update Posted: 2016-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 680

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DHA-P 7 days	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
DHA-P 14 days	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
Chloroquine 7 days	Chloroquine	Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
Chloroquine 14 days	Chloroquine	Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Shoklo Malaria Research Unit; 🇹🇭 Mae Sot, Tak, Thailand