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

Study Overview
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Brief Summary
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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
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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

Conditions
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Vivax Malaria

Intervention / Treatment
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* Drug: Dihydroartemisinin-Piperaquine
* Drug: Dihydroartemisinin-Piperaquine
* Drug: Chloroquine
* Drug: Chloroquine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHA-P 7 days<br>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<br>* 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<br>|
| Experimental: DHA-P 14 days<br>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<br>* 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<br>|
| Active Comparator: Chloroquine 7 days<br>Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days | Drug: Chloroquine<br>* Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days<br>|
| Active Comparator: Chloroquine 14 days<br>Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days | Drug: Chloroquine<br>* o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vivax, Chloroquine, Primaquine, Dihydroartemisinin-Piperaquine