Malaria Elimination Pilot Study in Military Forces in Cambodia

NCT02653898 | Unknown Phase 4

• 1 other identifier: WR2211
• Study Type: interventional
• Target: 1,050
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria; Parasitic Diseases

Keywords

Malaria; Antimalarials; Malaria Elimination; Mass Drug Administration; Malaria Prophylaxis; Mobile population; Drug resistance; Focused screening and treatment; Monthly Malaria Prophylaxis; Mass screening and treatment; Primaquine; Malaria transmission; Permethrin insecticide; Thai-Cambodian border; Cambodia; AFRIMS

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (12)

• 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.

  6 months

• Number of participants with abnormal lab values and/or Adverse Events that are related to the treatments in each arm

  6 months

• Kaplan-Meier survival analysis of asexual and sexual blood stage at 28-day intervals after treatment or prophylaxis up to 180 days

  6 months

• Comparison of all-species and species-specific malaria incidence density in each arm over 180-day period

  6 months

• Comparative incidence of malaria detected by RDT versus RT-PCR versus microscopy

  6 months

Study Arms (4)

Focused Screening and Treatment + ITU

ACTIVE COMPARATOR

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.

Drug: DHA-PIP; Drug: Primaquine; Drug: Artesunate + Mefloquine; Drug: Permethrin (Insecticide treated uniform)

Focused Screening and Treatment + sITU

ACTIVE COMPARATOR

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.

Drug: DHA-PIP; Drug: Primaquine; Drug: Artesunate + Mefloquine

Monthly Malaria Prophylaxis + ITU

ACTIVE COMPARATOR

Monthly DHA-PIP + weekly Primaquine 22.5 mg for 3 months; All subjects will also receive insecticide treated uniforms with 40% Permethrin

Drug: DHA-PIP; Drug: Primaquine; Drug: Permethrin (Insecticide treated uniform)

Monthly Malaria Prophylaxis + sITU

ACTIVE COMPARATOR

Monthly DHA-PIP + weekly Primaquine 22.5 mg for 3 months; All subjects will also receive sham treated uniforms

Drug: DHA-PIP; Drug: Primaquine

Interventions

DHA-PIP DRUG

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

Also known as: DHA-piperaquine, Dihydroartemisinin-piperaquine

Focused Screening and Treatment + ITU; Focused Screening and Treatment + sITU; Monthly Malaria Prophylaxis + ITU; Monthly Malaria Prophylaxis + sITU

Primaquine DRUG

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

Focused Screening and Treatment + ITU; Focused Screening and Treatment + sITU; Monthly Malaria Prophylaxis + ITU; Monthly Malaria Prophylaxis + sITU

Artesunate + Mefloquine DRUG

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

Also known as: ASMQ, Artesunate-Mefloquine

Focused Screening and Treatment + ITU; Focused Screening and Treatment + sITU

Permethrin (Insecticide treated uniform) DRUG

40% Permethrin IDA kit, applied once to the uniforms for volunteers assigned to ITU arm

Focused Screening and Treatment + ITU; Monthly Malaria Prophylaxis + ITU

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Armed Forces Research Institute of Medical Sciences, Thailand: lead
• National Center for Parasitology, Entomology, and Malaria Control (CNM): collaborator
• Ministry of National Defense, Royal Cambodian Armed Forces Department of Health: collaborator

Study Sites (1)

RCAF treatment facilities

Anlong Veaeng, Oddar Meancheay, Cambodia

Location

Related Publications (1)

• Manning J, Lon C, Spring M, Wojnarski M, Somethy S, Chann S, Gosi P, Soveasna K, Sriwichai S, Kuntawunginn W, Fukuda MM, Smith PL, Rekol H, Sinoun M, So M, Lin J, Satharath P, Saunders D. Cluster-randomized trial of monthly malaria prophylaxis versus focused screening and treatment: a study protocol to define malaria elimination strategies in Cambodia. Trials. 2018 Oct 16;19(1):558. doi: 10.1186/s13063-018-2931-x.

  PMID: 30326952 DERIVED

MeSH Terms

Conditions

Malaria; Parasitic Diseases

Interventions

Primaquine; Artesunate; Mefloquine; Permethrin

Condition Hierarchy (Ancestors)

Protozoan Infections; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Pyrethrins; Cyclopentane Monoterpenes; Monoterpenes

Study Officials

• Chanthap Lon, MD

  Armed Forces Research Institute of Medical Sciences, Thailand

  PRINCIPAL INVESTIGATOR

• Mariusz Wojnarski, MD

  Armed Forces Research Institute of Medical Sciences, Thailand

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 13, 2016
• Study Start: January 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2021
• Last Updated: March 2, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)