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

University of Oxford

Status and phase

Completed

Phase 3

Conditions

Vivax Malaria

Treatments

Drug: Dihydroartemisinin-Piperaquine

Drug: Chloroquine

Study type

Interventional

Funder types

Other

Identifiers

NCT01640574

SMRU1102

Details and patient eligibility

About

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.

Enrollment

680 patients

Sex

All

Ages

6+ months old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

680 participants in 4 patient groups

DHA-P 7 days

Experimental group

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

Treatment:

Drug: Dihydroartemisinin-Piperaquine

DHA-P 14 days

Experimental group

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

Treatment:

Drug: Dihydroartemisinin-Piperaquine

Chloroquine 7 days

Active Comparator group

Description:

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

Treatment:

Drug: Chloroquine

Chloroquine 14 days

Active Comparator group

Description:

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