A Revised Tafenoquine Dose to Improve Radical Cure for Vivax Malaria

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the efficacy and safety or a revised weight band tafenoquine dose in vivax malaria patients. The main question[s] it aims to answer are: is a revised weight-based TQ regimen (TQRevised: target dose 7.5mg/kg) non-inferior to high dose primaquine (7mg/kg over 7 days) is a revised weight-based TQ regimen (TQRevised: target dose 7.5mg/kg) superior to fixed dose tafenoquine (300mg) is the tolerability and safety of TQRevised acceptable is TQRevised acceptable and feasible Participants will receive a tafenoquine target dose 7.5mg/kg in weight bands. Researchers will compare this to patients receiving a fixed dose tafenoquine and high dose primaquine to see if safe and effective.

Official Title
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A Revised Tafenoquine Dose to Improve Radical Cure for Vivax Malaria - TAfenoquine DOsing REvised

Conditions
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Vivax Malaria

Intervention / Treatment
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* Drug: Tafenoquine
* Drug: Primaquin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: P. vivax peripheral parasitaemia (mono-infection) G6PD normal status (G6PD activity ≥70% of the adjusted male median as determined by the Standard G6PD (SDBioline, ROK)) Fever (temperature ≥37.5⁰C) or history of fever in the preceding 48 hours Written informed consent Living in the study area and willing to be followed for six months Exclusion Criteria: Danger signs or symptoms of severe malaria Anaemia (defined as Hb <8g/dl) Pregnant or lactating females Regular use of drugs with haemolytic potential Known hypersensitivity to any of the study drugs.

Ages Eligible for Study
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Minimum Age: 18 Years

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: TQRevised<br>Patients are treated with schizontocidal treatment plus a single weight-based dose of TQ (target dose 7.5mg/kg) | Drug: Tafenoquine<br>* see arm/group description<br>|
| Active Comparator: TQStandard<br>Patients are treated with schizontocidal treatment plus single fixed dose of 300mg TQ (TQStandard) | Drug: Tafenoquine<br>* see arm/group description<br>|
| Experimental: PQ7<br>Patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) over 7 days (PQ7) | Drug: Primaquin<br>* see arm/group description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence risk of vivax parasitaemia | The incidence risk (time to first event) of any P. vivax parasitaemia during the 4-month follow up period as determined by microscopy. compared between TQRevised and the PQ7 (non-inferiority) compared between TQRevised and TQStandard (superiority) | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence risk of vivax parasitaemia | The incidence risk (time to first event) of any P. vivax parasitaemia during the 4-month follow up period as determined by microscopy compared between TQStandard and PQ7 | 4 months | 
| The incidence risk of symptomatic vivax parasitaemia | The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 4 months follow up period as determined by microscopy | 4 months | 
| The incidence risk of vivax parasitaemia | The incidence risk (time to first event) of any P. vivax parasitaemia at 6-month follow up as determined by microscopy | 6 months | 
| The incidence risk of symptomatic vivax parasitaemia | The incidence risk (time to first event) of symptomatic P. vivax parasitaemia at 6-month follow up as determined by microscopy | 6 months | 
| The incidence rate of vivax parasitaemia | The incidence rate (events per person-time) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy | 6 months | 
| The incidence rate of symptomatic vivax parasitaemia | The incidence rate (events per person-time) of symptomatic P. vivax parasitaemia during the 6 months follow up period as determined by microscopy | 6 months | 
| The incidence risk of anaemia | The incidence risk of developing severe anaemia (Hb < 5g/dl) or moderate (5g/dl and <7g/dl) anaemia within 7 and 14 days of starting treatment and/or requiring blood transfusion within the 6 months follow up period | 7 and 14 days, 6 months | 
| The incidence risk of an acute drop in Hb | The incidence risk of an acute drop in Hb of >25% to <7g/dl within 7 and 14 days of starting treatment | 7 and 14 days | 
| Adverse events | The number and proportion of adverse and serious adverse events in each arm within 42 days after start of treatment | 42 days | 
| Meth Hb concentration | day 7 methaemoglobin concentration | day 7 |