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

Condition(s) targeted: Vivax Malaria

Intervention: Dihydroartemisinin-Piperaquine (Drug); Dihydroartemisinin-Piperaquine (Drug); Chloroquine (Drug); Chloroquine (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Oxford

Official(s) and/or principal investigator(s):
Francois Nosten, MD, Principal Investigator, Affiliation: University of Oxford
Cindy Chu, MD, Principal Investigator, Affiliation: Shoklo Malaria Research Unit

Overall contact:
Cindy Chu, MD, Phone: +66 55 545021, Email: cindy@shoklo-unit.com

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.

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Recurrence of P. vivax

Secondary outcome:

Adverse Events

Recurrence of P. vivax

Drug concentrations

Minimum age: 6 Months. Maximum age: N/A. Gender(s): Both.

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

Cindy Chu, MD, Phone: +66 55 545021, Email: cindy@shoklo-unit.com

Shoklo Malaria Research Unit, Mae Sot, Tak 63110, Thailand; Recruiting
Cindy Chu, MD, Phone: +66 55 545021, Email: cindy@shoklo-unit.com
Cindy Chu, MD, Principal Investigator

Starting date: July 2012
Last updated: August 28, 2013