Clinical trial NCT01280162: Malaria Active Epidemiology and Treatment Study
Official title: An Active Malaria Epidemiology Cohort Study With Evaluation of a 2 Day Versus 3 Day Treatment Regimen of Dihydroartemisinin (DHA)-Piperaquine for Patients With Uncomplicated Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Keywords: Plasmodium falciparum, Plasmodium vivax
Lead sponsor: Armed Forces Research Institute of Medical Sciences, Thailand
Sponsor class: OTHER_GOV
Collaborators: name: United States Army Medical Materiel Development Activity
First posted: 2011-01-20
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An observational cohort and malaria treatment study in Cambodia.

Detailed description: This is an active observational Cohort Study of malaria epidemiology with a nested two arm, randomized, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a two versus three day course of Dihydroartemisinin-Piperaquine (DP) for those developing uncomplicated malaria. At the conclusion of the Cohort Study, a subset of volunteers with documented exposure to Plasmodium vivax during the study will be treated with primaquine as presumptive anti-relapse therapy directed against the exoerythrocytic malaria stages of P. vivax, and followed passively for an additional 6 months.

Eligibility criteria: Inclusion Criteria:

1. Otherwise healthy volunteer, 18-65 years of age, eligible for care at an RCAF facility, and at risk for contracting malaria
2. Able to provide informed consent
3. Likely to reside in endemic area for the duration of the study
4. Available for follow-up for anticipated study duration, and agrees to participate for the duration of the study
5. Authorized by local commander to participate in the study if on active duty

Exclusion Criteria:

1. History of allergic reaction or contraindication to DHA or piperaquine
2. Significant acute comorbidity requiring urgent medical intervention
3. Pregnant or lactating female, or a female of childbearing age who does not agree to use a highly effective method of birth control during the study
4. Clinically significant abnormal EKG, including a QTc interval \> 500 ms.
5. Judged by the investigator to be otherwise unsuitable for study participation

Primary outcomes:
measure: Adequate clinical and parasitological response to a treatment regimen of DHA-PIP for Plasmodium falciparum
timeFrame: 6 months
Secondary outcomes:
measure: Number of Cambodian study subjects with reduced or null activity hepatic cytochrome P450 2D6 alleles
timeFrame: 1 year
measure: Number of subjects with reduced or null hepatic CYP2D6 enzyme phenotype using activity-score A system
timeFrame: 1 year
Other outcomes:
Locations:
city: Anlong Veng
country: Cambodia
facility: Oddar Meancheay
Study officials:
affiliation: USAMC-AFRIMS
name: Michele D. Spring, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lon C, Manning JE, Vanachayangkul P, So M, Sea D, Se Y, Gosi P, Lanteri C, Chaorattanakawee S, Sriwichai S, Chann S, Kuntawunginn W, Buathong N, Nou S, Walsh DS, Tyner SD, Juliano JJ, Lin J, Spring M, Bethell D, Kaewkungwal J, Tang D, Chuor CM, Satharath P, Saunders D. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial. PLoS One. 2014 Mar 25;9(3):e93138. doi: 10.1371/journal.pone.0093138. eCollection 2014.
citation: Vanachayangkul P, Lon C, Spring M, Sok S, Ta-Aksorn W, Kodchakorn C, Pann ST, Chann S, Ittiverakul M, Sriwichai S, Buathong N, Kuntawunginn W, So M, Youdaline T, Milner E, Wojnarski M, Lanteri C, Manning J, Prom S, Haigney M, Cantilena L, Saunders D. Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02000-16. doi: 10.1128/AAC.02000-16. Print 2017 May.
citation: Spring MD, Pichyangkul S, Lon C, Gosi P, Yongvanichit K, Srichairatanakul U, Limsalakpeth A, Chaisatit C, Chann S, Sriwichai S, Auayapon M, Chaorattanakawee S, Dutta S, Prom S, Meng Chour C, Walsh DS, Angov E, Saunders DL. Antibody profiles to plasmodium merozoite surface protein-1 in Cambodian adults during an active surveillance cohort with nested treatment study. Malar J. 2016 Jan 8;15:17. doi: 10.1186/s12936-015-1058-8.
citation: Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, Se Y, Chann S, Ittiverakul M, Sia-ngam P, Kuntawunginn W, Arsanok M, Buathong N, Chaorattanakawee S, Gosi P, Ta-aksorn W, Chanarat N, Sundrakes S, Kong N, Heng TK, Nou S, Teja-isavadharm P, Pichyangkul S, Phann ST, Balasubramanian S, Juliano JJ, Meshnick SR, Chour CM, Prom S, Lanteri CA, Lon C, Saunders DL. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015 Jun;15(6):683-91. doi: 10.1016/S1473-3099(15)70049-6. Epub 2015 Apr 12.