- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02653898
Malaria Elimination Pilot Study in Military Forces in Cambodia
Defining Effective, Appropriate, Implementable Strategies for Malaria Elimination in Military Forces in Cambodia as a Model for Mobile Populations
Antimalarial drug resistance has reached critical levels on the Thai-Cambodian border. Many have begun advocating for concerted malaria elimination efforts in Cambodia. However, there is currently no consensus on how malaria elimination is to be achieved with the tools available.
In this study, the investigators will conduct operational research with the Royal Cambodian Armed Forces (RCAF) and National Malaria Center (CNM) to quantify the relative effectiveness of the two major interventional approaches - monthly malaria prophylaxis (MMP) or focused screening and treatment (FSAT) - in a head to-head comparison. In addition, the investigators will quantify the relative contribution of a recently advocated vector intervention for military personnel - the insecticide treated uniform (ITU) - in addition to other vector control measures currently employed by the RCAF. The investigators will employ the same permethrin insecticide self-application kits currently used by the US military. The investigators will estimate the cost effectiveness of each approach and attempt to define the best way forward for malaria elimination efforts in a critically important malaria reservoir in military population (and their dependents) who reside on the Thai-Cambodian border. The aim of the study is not only to conduct research to better define the best way forward in malaria elimination efforts in the high risk military populations, but to also build capacity within the RCAF to support and lead future elimination efforts in the most difficult-to-reach mobile populations.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Oddar Meancheay
-
Anlong Veng, Oddar Meancheay, Cambodia
- RCAF treatment facilities
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Military volunteers aged 18-65 years of age plus their dependents > 2 years of age, eligible for care at an RCAF facility, or otherwise eligible Cambodian civilians at risk for contracting malaria who live within the designated geographical areas
- Able to give informed consent/assent
- Resides in the selected study areas, and available for monthly follow-up for 6 month study duration
- Agrees not to seek outside medical care for febrile illness unless referred by study team
- Authorized by local commander to participate in the study if on active duty
Exclusion Criteria:
- Allergic reaction or contraindication to dihydroartemisinin-piperaquine or primaquine or artesunate+mefloquine
- Pregnant or lactating female, or female of childbearing age, up to 50 years of age or otherwise individually assessed for childbearing potential, who does not agree to use an acceptable form of contraception during the study
- Judged by the investigator to be otherwise unsuitable for study participation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Focused Screening and Treatment + ITU
Approved antimalarial based on the malaria species identified on the monthly follow ups, following national treatment guidelines in Cambodia AND Insecticide Treated Uniform with 40% Permethrin; DHA-PIP or Artesunate + Mefloquine based on the malaria species, single dose Primaquine 15 mg in subjects with P.f uncomplicated malaria or Primaquine 45 mg weekly x 8 weeks in G6PD-deficient volunteers, or Primaquine 15 mg daily for 14 days in G6PD-normal volunteers.
|
Administered monthly (weight-based) on days 1-3, during months 1, 2, and 3 in the MMP arm and also as a first line agent for P.v malaria recurrence in both MMP and FSAT treatment arms
Other Names:
22.5 mg weekly for 12 weeks in the MMP arm; low dose primaquine (15mg) for transmission blocking of P. falciparum or 14 days of primaquine (15mg) in G6PD normal volunteers or 8 weeks of low dose primaquine (45mg) in G6PD-deficient volunteers for radical cure of P. vivax
Weight based; first line agent for P.f malaria infection diagnosed at monthly follow ups, administered on days 1-3 in subjects with malaria recurrence
Other Names:
40% Permethrin IDA kit, applied once to the uniforms for volunteers assigned to ITU arm
|
ACTIVE_COMPARATOR: Focused Screening and Treatment + sITU
Approved antimalarial based on the malaria species identified at the monthly follow up and following national treatment guidelines in Cambodia AND sham treated uniform.
DHA-PIP or Artesunate + Mefloquine based on the malaria species, single dose Primaquine 15 mg in subjects with P.f uncomplicated malaria or Primaquine 45 mg weekly x 8 weeks in G6PD-deficient volunteers, or Primaquine 15 mg daily for 14 days in G6PD-normal volunteers.
|
Administered monthly (weight-based) on days 1-3, during months 1, 2, and 3 in the MMP arm and also as a first line agent for P.v malaria recurrence in both MMP and FSAT treatment arms
Other Names:
22.5 mg weekly for 12 weeks in the MMP arm; low dose primaquine (15mg) for transmission blocking of P. falciparum or 14 days of primaquine (15mg) in G6PD normal volunteers or 8 weeks of low dose primaquine (45mg) in G6PD-deficient volunteers for radical cure of P. vivax
Weight based; first line agent for P.f malaria infection diagnosed at monthly follow ups, administered on days 1-3 in subjects with malaria recurrence
Other Names:
|
ACTIVE_COMPARATOR: Monthly Malaria Prophylaxis + ITU
Monthly DHA-PIP + weekly Primaquine 22.5 mg for 3 months; All subjects will also receive insecticide treated uniforms with 40% Permethrin
|
Administered monthly (weight-based) on days 1-3, during months 1, 2, and 3 in the MMP arm and also as a first line agent for P.v malaria recurrence in both MMP and FSAT treatment arms
Other Names:
22.5 mg weekly for 12 weeks in the MMP arm; low dose primaquine (15mg) for transmission blocking of P. falciparum or 14 days of primaquine (15mg) in G6PD normal volunteers or 8 weeks of low dose primaquine (45mg) in G6PD-deficient volunteers for radical cure of P. vivax
40% Permethrin IDA kit, applied once to the uniforms for volunteers assigned to ITU arm
|
ACTIVE_COMPARATOR: Monthly Malaria Prophylaxis + sITU
Monthly DHA-PIP + weekly Primaquine 22.5 mg for 3 months; All subjects will also receive sham treated uniforms
|
Administered monthly (weight-based) on days 1-3, during months 1, 2, and 3 in the MMP arm and also as a first line agent for P.v malaria recurrence in both MMP and FSAT treatment arms
Other Names:
22.5 mg weekly for 12 weeks in the MMP arm; low dose primaquine (15mg) for transmission blocking of P. falciparum or 14 days of primaquine (15mg) in G6PD normal volunteers or 8 weeks of low dose primaquine (45mg) in G6PD-deficient volunteers for radical cure of P. vivax
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The absolute risk reduction based on the proportion of subjects remaining malaria-free at the end of 6 months between the study arms as diagnosed by PCR-corrected malaria microscopy
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall rate of sexual stage infections at Months 1 through 6 in each arm based on a combined endpoint of light microscopy and PCR analysis for detection of gametocyte maturity.
Time Frame: 6 months
|
6 months
|
Number of participants with abnormal lab values and/or Adverse Events that are related to the treatments in each arm
Time Frame: 6 months
|
6 months
|
Kaplan-Meier survival analysis of asexual and sexual blood stage at 28-day intervals after treatment or prophylaxis up to 180 days
Time Frame: 6 months
|
6 months
|
Comparison of all-species and species-specific malaria incidence density in each arm over 180-day period
Time Frame: 6 months
|
6 months
|
Comparative incidence of malaria detected by RDT versus RT-PCR versus microscopy
Time Frame: 6 months
|
6 months
|
Comparative incidence of G6PD deficiency in the study population as determined by RDT, quantitative, and qualitative tests
Time Frame: At the time of enrollment
|
At the time of enrollment
|
Estimate of apparent rates of preexisting immunity to malaria based on medical history, days of fever prior to presentation, and preexisting parasitological parameters (gametocytemia, low asexual stage parasitemias)
Time Frame: 6 months
|
6 months
|
Sensitivity and specificity assessment of the currently recommended rapid diagnostic test in Cambodia to detect moderate to severe G6PD deficiency using quantitative G6PD testing as the reference standard
Time Frame: At the time of enrollment
|
At the time of enrollment
|
Odds ratio for P.v recurrence for each CYP2D6 phenotype
Time Frame: 6 months
|
6 months
|
Rate of cytochrome P450 2D6 genotypes/phenotypes in the population at risk
Time Frame: 6 months
|
6 months
|
Percent reduction in hemoglobin and HTC for each 2D6 haplotype in subjects with available CBC following PQ dosing
Time Frame: Day 3 (and day 7 in those volunteers with Hgb or HCT drop of at least 10% from baseline on Day 3)
|
Day 3 (and day 7 in those volunteers with Hgb or HCT drop of at least 10% from baseline on Day 3)
|
Percentage of subjects with malaria recurrence for each CYP2D6 phenotype
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Mariusz Wojnarski, MD, Armed Forces Research Institute of Medical Sciences, Thailand
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Malaria
- Drug resistance
- Malaria Prophylaxis
- Cambodia
- Primaquine
- Mass Drug Administration
- Antimalarials
- Malaria Elimination
- Mobile population
- Focused screening and treatment
- Monthly Malaria Prophylaxis
- Mass screening and treatment
- Malaria transmission
- Permethrin insecticide
- Thai-Cambodian border
- AFRIMS
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Protozoan Infections
- Malaria
- Parasitic Diseases
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Anthelmintics
- Schistosomicides
- Antiplatyhelmintic Agents
- Permethrin
- Primaquine
- Artesunate
- Piperaquine
- Artenimol
- Mefloquine
Other Study ID Numbers
- WR2211
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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