Prevention of Malaria With Dihydroartemisinine + Piperaquine for Forest Rangers

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess if the antimalarial drugs Dihydroartemisinine + Piperaquine (DP) are effective in preventing malaria infection for forest ranger

Detailed Description
-----------------
To assess the protective effect of 3-day DP regimen for forest rangers working for long-term in forest where malaria transmission is intense, all eligible forest rangers will be treated with a full course of DP + primaquine to eradicate all parasites which may survive in their blood while staying in non- malaria transmission areas. Just before returning back to the forest participants will be randomized to receive either Arterakine (dihydroartemisinine (DHA)/piperaquine) (intervention arm) or placebo (control arm). Participants will be assessed for parasitemia before and after the forest trip with high volume, ultrasensitive, PCR (HVUqPCR). The minimum time span between two forest trips should be 20 days so participants could complete the 14 day primaquine course and the Arterakine (dihydroartemisinine (DHA)/piperaquine). There is no limit in the duration between trips. Participants are tested for P.falciparum, P.vivax infection before they return to the forest. Each participant will be visited 2 weeks or later after returning home from the forest and examined. The rationale for the added two weeks is to detect blood stages of infections, which may have been inoculated towards the end of the forest visit. If found to be sick, the patient will be treated according to government treatment guidelines. A 4ml venous blood sample will be obtained for Hb and HVUSqPCR.

Official Title
-----------------
A Randomized, Placebo-controlled, Double-blind Trial Using Dihydroartemisinine+Piperaquine (DP) to Protect Forest Workers From Malaria in Bu Gia Map National Park

Conditions
-----------------
Malaria

Intervention / Treatment
-----------------
* Drug: Arterakine (DHA/piperaquine)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent Male, over or equal to18 years of age Able and willing to comply with the study requirements and follow-up Exclusion Criteria: Inability to tolerate oral treatment Previous episode of haemolysis or severe haemoglobinuria following primaquine Glucose-6-phosphate dehydrogenase (G6PD) deficient with Hb < 9 g/dL * Known hypersensitivity or allergy to any study drugs * If the participant with G6PD deficient gets malaria, primaquine would be used as recommended by World Health Organization (WHO) (once a week for 8 weeks) in combination with 3 days of chloroquine.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arterakine<br>Active drug: Arterakine (DHA/piperaquine) one tablet contains 40 mg of dihydroartemisinin and 320 mg piperaquine. Weight based regimen: 7 mg/kg dihydroartemisinin; 55 mg/kg piperaquine phosphate) for 3 days prior to forest visit (day -2, -1 and day 0 prior forest visit) | Drug: Arterakine (DHA/piperaquine)<br>* Stage 1: Parasite Clearance Arterakine (DHA/piperaquine), one tablet contains 40 mg of dihydroartemisinine and 320 mg piperaquine. Weight based regimen: 7 mg/kg dihydroartemisinine; 55 mg/kg piperaquine phosphate) for 3 days Primaquine (One tablet contains 13.2mg primaquine disphosphate/7.5mg base. Weight based regimen: 0.25mg base/kg) for 14 days Stage 2: Forest trip • Arterakine (DHA/piperaquine), one tablet contains 40 mg of dihydroartemisinine and 320 mg piperaquine. Weight based regimen: 7 mg/kg dihydroartemisinine; 55 mg/kg piperaquine phosphate) for 3 days prior to forest visit (day -2, -1 and day 0 prior forest visit)<br>|
| Placebo Comparator: Placebo<br>Placebo (visually matched to Arterakine for 3 days prior to forest visit (day -2, -1 and day 0 prior forest visit) | Drug: Placebo<br>* Stage 1: Parasite Clearance Arterakine (DHA/piperaquine), one tablet contains 40 mg of dihydroartemisinine and 320 mg piperaquine. Weight based regimen: 7 mg/kg dihydroartemisinine; 55 mg/kg piperaquine phosphate) for 3 days Primaquine (One tablet contains 13.2mg primaquine disphosphate/7.5mg base. Weight based regimen: 0.25mg base/kg) for 14 days Stage 2: Forest trip • Placebo (visually matched to Arterakine (DHA/piperaquine) for 3 days prior to forest visit (day -2, -1 and day 0 prior forest visit)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of study subjects with any malaria parasitaemia (P.falciparum, mixed parasitaemia of P.falciparum and P.vivax) and the incidence rate of symptomatic malaria | The primary endpoints are the proportion of study subjects with any malaria parasitaemia (P.falciparum, mixed parasitaemia of P.falciparum and P.vivax) at 2 weeks after coming back from the forest assessed by high volume, ultrasensitive PCR (HVUSqPCR) and the incidence rate of symptomatic malaria (P.falciparum, mixed P.falciparum + P.vivax) during the two week follow-up period as assessed by the study doctor. | at 2 weeks after coming back from the forest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of different anopheles species amongst all captured mosquito anopheles | The proportion of different anopheles species amongst all captured mosquito anopheles as identified by morphology | 1 month | 
| The proportion of sporozoite-carrying mosquitoes (any parasite, P.falciparum, mixed P.falciparum and P.vivax) | The proportion of sporozoite-carrying mosquitoes (any parasite, P.falciparum, mixed P.falciparum and P.vivax) as assessed by PCR. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Forest ranger, P.falciparum, P.vivax, Dihydroartemisinine-piperaquine (DP), Primaquine