P.Vivax Treatment Trial

Study Overview
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Brief Summary
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This study aims to determine whether a 14 day course of 0.5 mg/kg/day primaquine can eliminate subclinical P. vivax infections detected by high volume ultra-sensitive PCR (uPCR).

Detailed Description
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This is a randomized, Single blind trial in G6PD normal participants with subclinical P. vivax infections in Laos. Participants with subclinical P. vivax infections and those meeting the enrolment criteria will be randomly assigned to one of two treatment arms: Intervention: Dihydroartemisinin-piperaquine (DP) therapy 3 days dosing plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg/day). Control arm: Dihydroartemisinin-piperaquine (DP) 3 days dosing therapy plus 14 days identical primaquine placebo. Participants found to be G6PD deficient (G6PDd) will be treated with primaquine 0.75mg/kg/week for 8 weeks according to WHO recommendations. Primaquine and placebo will be administered with food (biscuits), which has been shown to reduce gastrointestinal side effects. All doses of study drugs will be supervised. If participants cannot visit the study centre, or fail to attend during the 14 days of supervised therapy, team members will visit them in their homes, schools or work to ensure complete dosing. Findings: The study showed that a 14-day course of primaquine added to mass drug administration with dihydroartemisinin-piperaquine prevented recurrent asymptomatic P. vivax infections (doi: 10.1186/s12936-019-3091-5)

Official Title
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A Randomised, Single-blinded Controlled Treatment Trial of Subclinical Vivax Infections With Primaquine in Nong Province, Laos

Conditions
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Plasmodium Vivax

Intervention / Treatment
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* Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)
* Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with subclinical mono- or mixed P. vivax infections (uPCR) can be enrolled. Able to participate as decided by the investigators, and willing to comply with the study requirements and follow-up. A participant (or parent/guardian of children below age of consent) is willing and able to give written informed consent to participate in the trial. Exclusion Criteria: Currently pregnant or breastfeeding (female of child-bearing age). Inability to tolerate oral treatment. Previous episode of haemolysis or severe haemoglobinuria following primaquine. Known hypersensitivity or allergy to the study drugs. Blood transfusion in last 90 days, since this can mask G6PD deficiency. An acute malaria episode requiring treatment. A febrile condition due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration). Anaemia (Haemoglobin (Hb) < 9 g/dL Presence of any condition which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal or hepatic disease; severe malnutrition; HIV/AIDS; or severe febrile condition other than malaria); co-administration of other medication known to cause haemolysis or that could interfere with the assessment of antimalarial regimens. Currently taking medication known to interfere significantly with the pharmacokinetics of primaquine and the schizontocidal study drugs

Ages Eligible for Study
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Minimum Age: 10 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention arm<br>Dihydroartemisinin-piperaquine (DP) therapy plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg). | Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ)<br> <br> |
| Placebo Comparator: Control arm<br>Dihydroartemisinin-piperaquine therapy plus 14 days identical placebo not containing primaquine. | Drug: Dihydroartemisinin-piperaquine (DP) + Primaquine (PQ) placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of P. vivax parasitaemia in G6PD-normal participants | the incidence rate will be detected by uPCR | over 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to P. vivax clearance | Detected by uPCR | 12 months | 
| The frequency of recurrent vivax infections (clinical and sub-clinical) |  | 12 months | 
| The follow-up period required to detect a statistically significant difference in the frequency of recurrent subclinical P. vivax infections between treated and untreated participants | measured by uPCR | 12 months | 
| Number of participants with treatment related Adverse event. |  | 28 days | 
| Number of participants with treatment related malaria episode |  | 12 months | 
| Number of doses taken per participants |  | 14 days | 
| Compare the percentage decrease in hemoglobin between those who receive primaquine and who those not receive primaquine |  | 12 months | 
| Number of G6PD genotypes in participants with G6PD deficiency |  | 12 months | 
| Number of P450 genotypes in participants with recurrent PV infection. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single-blinded controlled trial, Primaquine