Short Course Radical Cure of P. Vivax Malaria in Nepal

Study Overview
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Brief Summary
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This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in glucose-6-phosphate dehydrogenase (G6PD) normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.

Detailed Description
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Plasmodium vivax is associated with recurrent infections weeks or months following the acute infection due to reactivation of dormant liver stages. Recurrent infections can be associated with a febrile illness, cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite. In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P.vivax malaria following treatment of P falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P.vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections. The recently completed multicentre IMPROV study compared the efficacy of a 7 day PQ regimen (1.0mg/kg/day for 7 days) with a 14 day regimen (0.5mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5 times more efficacious at reducing P.vivax recurrence than the control. This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in G6PD normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.

Official Title
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Short Course Radical Cure of P.Vivax in Nepal- a Randomized Controlled Trial

Conditions
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Malaria, Malaria, Vivax, Malaria,Falciparum

Intervention / Treatment
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* Drug: primaquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: P. falciparum and/or vivax infection Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours Age >1 years G6PD normal by Rapid Diagnostic Test (RDT) as per national guidelines Written informed consent Able to comply with all study procedures and timelines Exclusion Criteria: General danger signs or symptoms of severe malaria Anaemia, defined as Hb <8g/dl Pregnant women as determined by Urine β-HCG pregnancy test Breast feeding women Known hypersensitivity to any of the drugs given Regular use of drugs with haemolytic potential Blood transfusion within the last 4 months

Ages Eligible for Study
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Minimum Age: 1 Year

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: (P.f)<br>patients with falciparum malaria will receive artemether-lumefantrine (AL) twice daily over three days plus a low dose course of primaquine (PQ) (3.5mg/kg total dose) given 7 days during schizontocidal treatment | Drug: primaquine<br>* Primaquine regimen over 7 days (0.5mg/kg/day for 7 days)<br>* Other names: Jasoprim, Malirid, Neo-Quipenyl, Pimaquin, Pmq, Primachina, Primacin, Primaquina, Primaquine, Primaquine diphosphate, Primaquine Phosphate, and Remaquin;|
| Experimental: (P.v)<br>patients with vivax malaria will receive chloroquine (CQ) daily for three days plus a low dose course of PQ (3.5mg/kg total dose) given over 7 days during schizontocidal treatment. | Drug: primaquine<br>* Primaquine regimen over 7 days (0.5mg/kg/day for 7 days)<br>* Other names: Jasoprim, Malirid, Neo-Quipenyl, Pimaquin, Pmq, Primachina, Primacin, Primaquina, Primaquine, Primaquine diphosphate, Primaquine Phosphate, and Remaquin;|
| No Intervention: Standard care (P.f)<br>patients with falciparum malaria will receive artemether-lumefantrine (AL) twice daily over three days (plus a single dose PQ) | |
| No Intervention: Standard care (P.v)<br>patients with vivax malaria will receive chloroquine (CQ) daily for three days plus a low dose course of PQ (total dose 3.5mg/kg) over 14 days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Risk of P. vivax relapse at month 6 | The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. vivax and P. falciparum infection. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. vivax |  | 6 months | 
| The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. falciparum |  | 6 month | 
| The incidence risk of symptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection |  | Day 28 | 
| The incidence risk of all (symptomatic and asymptomatic) P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection |  | Day 28 | 
| The incidence risk of asymptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection |  | Day 28 |