Prevention of Malaria With Dihydroartemisinine + Piperaquine for Forest Rangers

Malaria Clinical Trial

— PREMAL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02788864
• Other study ID #: 17MA
• Status: Completed
• Phase: Phase 4
• First received: May 27, 2016
• Last updated: March 6, 2017
• Start date: May 20, 2016
• Est. completion date: November 30, 2016

Study information

• Verified date: March 2017
• Source: Oxford University Clinical Research Unit, Vietnam
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 30, 2016
• Est. primary completion date: November 30, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent

2. Male, over or equal to18 years of age

3. Able and willing to comply with the study requirements and follow-up

Exclusion Criteria:

1. Inability to tolerate oral treatment

2. Previous episode of haemolysis or severe haemoglobinuria following primaquine

3. Glucose-6-phosphate dehydrogenase (G6PD) deficient with Hb < 9 g/dL *

4. 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.

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Arterakine (DHA/piperaquine)
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)
• Placebo
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)

Locations

Country	Name	City	State
Vietnam	Bu Gia Map Commune Health Station	Binh Phuoc

Sponsors (3)

Lead Sponsor	Collaborator
Oxford University Clinical Research Unit, Vietnam	Binh Phuoc Malaria Control Centre, Bu Gia Map National Park, Binh Phuoc Province, Vietnam

Country where clinical trial is conducted

Vietnam, 

References & Publications (8)

Abe T, Honda S, Nakazawa S, Tuong TD, Thieu NQ, Hung le X, Thuan le K, Moji K, Takagi M, Yamamoto T. Risk factors for malaria infection among ethnic minorities in Binh Phuoc, Vietnam. Southeast Asian J Trop Med Public Health. 2009 Jan;40(1):18-29. — View Citation

Erhart A, Ngo DT, Phan VK, Ta TT, Van Overmeir C, Speybroeck N, Obsomer V, Le XH, Le KT, Coosemans M, D'alessandro U. Epidemiology of forest malaria in central Vietnam: a large scale cross-sectional survey. Malar J. 2005 Dec 8;4:58. — View Citation

Erhart A, Thang ND, Hung NQ, Toi le V, Hung le X, Tuy TQ, Cong le D, Speybroeck N, Coosemans M, D'Alessandro U. Forest malaria in Vietnam: a challenge for control. Am J Trop Med Hyg. 2004 Feb;70(2):110-8. — View Citation

Imwong M, Hanchana S, Malleret B, Rénia L, Day NP, Dondorp A, Nosten F, Snounou G, White NJ. High-throughput ultrasensitive molecular techniques for quantifying low-density malaria parasitemias. J Clin Microbiol. 2014 Sep;52(9):3303-9. doi: 10.1128/JCM.01057-14. — View Citation

Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, Suangkanarat P, Jeeyapant A, Vihokhern B, Wongsaen K, Van Hue D, Dong le T, Nguyen TU, Lubell Y, von Seidlein L, Dhorda M, Promnarate C, Snounou G, Malleret B, Rénia L, Keereecharoen L, Singhasivanon P, Sirithiranont P, Chalk J, Nguon C, Hien TT, Day N, White NJ, Dondorp A, Nosten F. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015 Sep 30;14:381. doi: 10.1186/s12936-015-0906-x. — View Citation

Parker DM, Carrara VI, Pukrittayakamee S, McGready R, Nosten FH. Malaria ecology along the Thailand-Myanmar border. Malar J. 2015 Oct 5;14:388. doi: 10.1186/s12936-015-0921-y. — View Citation

Sanh NH, Van Dung N, Thanh NX, Trung TN, Van Co T, Cooper RD. Forest malaria in central Vietnam. Am J Trop Med Hyg. 2008 Nov;79(5):652-4. — View Citation

Thanh PV, Van Hong N, Van Van N, Van Malderen C, Obsomer V, Rosanas-Urgell A, Grietens KP, Xa NX, Bancone G, Chowwiwat N, Duong TT, D'Alessandro U, Speybroeck N, Erhart A. Epidemiology of forest malaria in Central Vietnam: the hidden parasite reservoir. Malar J. 2015 Feb 19;14:86. doi: 10.1186/s12936-015-0601-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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