Malaria Elimination Pilot Study in Military Forces in Cambodia

NCT ID: NCT02653898

Last Updated: 2021-03-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 1050 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2021-12-31

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.

Detailed Description

This is a cluster-randomized, open label interventional study to determine the feasibility of achieving significant reduction in malaria cases in military encampments on the Thai-Cambodian border. The study will compare the effectiveness, safety, and tolerability of monthly malaria prophylaxis (MMP) to monthly focused screening and treatment (FSAT). This study will thus investigate the effectiveness of two potential interventions for malaria elimination. Subjects in the monthly malaria prophylaxis (MMP) arm will receive a standard 3-day treatment course of dihydroartemisinin-piperaquine on months 1, 2 and 3 and weekly low-dose primaquine (22.5mg for 12 weeks). Volunteers in the focused screening and treatment (FSAT) arm will be screened monthly and then treated for malaria following national treatment guidelines. For G6PD-deficient volunteers in the FSAT arm, primaquine will be administered weekly (45mg for 8 weeks) as radical curative and/or presumptive anti-relapse therapy. For G6PD normal volunteers with vivax infection, primaquine will be administered daily (15mg for 14 days). All FSAT volunteers with confirmed P. falciparum infection will receive a single, low dose (15mg) Primaquine as a P. falciparum transmission-blocking agent. The incremental benefit of an insecticide treated uniform (ITU) will also be assessed as a single-blind sham-controlled intervention in addition to personal protective measures currently employed by the RCAF. Volunteers will be followed monthly for a total of 6 months, to determine the proportion remaining malaria-free on day 180 following enrollment.

Conditions

Malaria; Parasitic Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

DHA-PIP

Intervention Type: 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

Primaquine

Intervention Type: 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

Artesunate + Mefloquine

Intervention Type: 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

Permethrin (Insecticide treated uniform)

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

DHA-PIP

Intervention Type: 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

Primaquine

Intervention Type: 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

Artesunate + Mefloquine

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

DHA-PIP

Intervention Type: 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

Primaquine

Intervention Type: 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

Permethrin (Insecticide treated uniform)

Intervention Type: DRUG

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

Monthly Malaria Prophylaxis + sITU

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

Group Type: ACTIVE_COMPARATOR

DHA-PIP

Intervention Type: 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

Primaquine

Intervention Type: 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

Interventions

DHA-PIP

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

Intervention Type: DRUG

Primaquine

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

Intervention Type: DRUG

Artesunate + Mefloquine

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

Intervention Type: DRUG

Permethrin (Insecticide treated uniform)

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

Intervention Type: DRUG

Other Intervention Names

DHA-piperaquine; Dihydroartemisinin-piperaquine; ASMQ; Artesunate-Mefloquine

Eligibility Criteria

Inclusion Criteria

1. 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

2. Able to give informed consent/assent

3. Resides in the selected study areas, and available for monthly follow-up for 6 month study duration

4. Agrees not to seek outside medical care for febrile illness unless referred by study team

5. Authorized by local commander to participate in the study if on active duty

Exclusion Criteria

1. Allergic reaction or contraindication to dihydroartemisinin-piperaquine or primaquine or artesunate+mefloquine

2. 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

3. Judged by the investigator to be otherwise unsuitable for study participation

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Parasitology, Entomology, and Malaria Control (CNM)

UNKNOWN

Sponsor Role: collaborator

Ministry of National Defense, Royal Cambodian Armed Forces Department of Health

UNKNOWN

Sponsor Role: collaborator

Armed Forces Research Institute of Medical Sciences, Thailand

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chanthap Lon, MD

Role: PRINCIPAL_INVESTIGATOR

Armed Forces Research Institute of Medical Sciences, Thailand

Mariusz Wojnarski, MD

Role: STUDY_CHAIR

Armed Forces Research Institute of Medical Sciences, Thailand

Locations

RCAF treatment facilities

Anlong Veaeng, Oddar Meancheay, Cambodia

Countries

Cambodia

References

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.

Reference Type: DERIVED

PMID: 30326952 (View on PubMed)

Other Identifiers

WR2211

Identifier Type: -

Identifier Source: org_study_id