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

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT01640574

Collaborator

(none)

680

Enrollment

Location

Arms

Duration (Months)

14.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Vivax Malaria	Drug: Dihydroartemisinin-Piperaquine Drug: Dihydroartemisinin-Piperaquine Drug: Chloroquine Drug: Chloroquine	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

680 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Jul 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months and Older

Sexes Eligible for Study:

All

Accepts 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