A Study to Assess Safety of Current Standard Malaria Treatment and an Assessment of G6PD Status in South-east Bangladesh

Study Overview
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Brief Summary
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This is a study assessing safety and efficacy of current national guidelines for the treatment of uncomplicated malaria in Bangladesh as well as to assess the G6PD status among the enrolled patients.

Detailed Description
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The national guidelines for the treatment of uncomplicated malaria in Bangladesh currently recommend a standard dose of artemether-lumefantrine followed by a single dose of primaquine for P. falciparum malaria and a three day course of chloroquine followed by 14 days of primaquine for vivax malaria.Currently the national treatment guidelines do not include any testing for G6PD deficiency before treatment with primaquine. In order to guarantee safe and efficacious treatment for all patients diagnosed with uncomplicated malaria in Bangladesh, it is essential to monitor the effectiveness and safety of the recommended treatment guidelines. This trial therefore evaluates the local efficacy and safety of the current first line treatment and assesses the G6PD status of the enrolled patients. Patients with uncomplicated malaria attending the health care center, who meet the study inclusion criteria will be enrolled, treated on site and followed up for 28 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. The study will provide efficacy data for both artemether-lumefantrine and chloroquine and will generate data on G6PD status in the region, which will provide vital information for policy makers in regards to the wider roll out of primaquine for the radical cure of vivax malaria.

Official Title
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A Study to Assess Safety of Current Standard Malaria Treatment and an Assessment of Glucose-6-dehydrogenase Status in South-east Bangladesh

Conditions
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Malaria

Intervention / Treatment
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* Drug: chloroquine
* Drug: Artemether-lumefantrine combination
* Drug: Primaquine
* Drug: Primaquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 12 months P. vivax or P. falciparum monoinfection or P.v. / P.f. mixed infection Presence of axillary temperature ≥ 37.5°C or history of fever during the past 24 hrs Ability to swallow oral medication. Ability and willingness to comply with the study protocol for the duration of the study Informed consent/assent from the patient or from a parent or guardian in the case of children. Exclusion Criteria: Presence of general danger signs in children aged under 5 years or signs of severe malaria according to the definitions of WHO Presence of severe malnutrition Acute anaemia <8g/dL Regular medication, which may interfere with antimalarial pharmacokinetics History of hypersensitivity reactions or contraindications to any of the drug(s) tested or used as alternative treatment(s) A positive pregnancy test or lactating

Ages Eligible for Study
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Minimum Age: 12 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: chloroquine primaquine 14days<br>P.vivax malaria patients receiving chloroquine and primaquine 14days as per guidelines | Drug: chloroquine<br>* standard dose<br>Drug: Primaquine<br>* 14 days<br>|
| Other: artemether-lumefantrine primaquine 1day<br>P.falciparum malaria patients receiving artemether-lumefantrine combination and primaquine 1day as per guidelines | Drug: Artemether-lumefantrine combination<br>* standard dose<br>Drug: Primaquine<br>* single dose<br>|
| Other: artemether-lumefantrine primaquine 14days<br>mixed malaria infection receiving artemether-lumefantrine combination and primaquine 14days as per guidelines | Drug: Artemether-lumefantrine combination<br>* standard dose<br>Drug: Primaquine<br>* 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Adverse and Serious Adverse Events Following Unsupervised Primaquine Treatment | The proportion of adverse and serious adverse events following unsupervised primaquine treatment until day 28 | during follow up (day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Receiving Blood Transfusion and With Severe Anaemia (Hb<7g/dl) |  | day 28 | 
| Fractional Change in Hb Between Baseline and Day 9 and 16 |  | day 0 and 16 | 
| Proportion of Patients With Anaemia Less Than 8g/dl on Day 2 |  | on day 2 | 
| Proportion of Patients With Any Parasitemia on Day 3 After Treatment |  | day 3 | 
| Proportion of Patients With Fever on Day 2 After Treatment |  | day 2 | 
| Recurrence of Parasitaemia Within 16 Days of Follow up |  | day 16 | 
| Proportion of Patients Adhering to 14 Days of Primaquine Treatment in the Vivax Cohort as Measured by Pill Count |  | day 16 | 
| The Distribution of G6PD Activity Measured in U/gHb Among All Malaria Patients |  | day 0 | 
| Frequency and Type of Variants of the G6PD Gene Within the Study Population | Frequency and type of variants of the G6PD gene within the study population | day 0 or 1 |