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Targeting High Risk Populations With Enhanced Reactive Focal Mass Drug Administration in Thailand (COMBAT)

Primary Purpose

Plasmodium Falciparum Malaria, Plasmodium Vivax Malaria

Status

Recruiting

Phase

Not Applicable

Locations

Thailand

Study Type

Interventional

Intervention

Case Management and Follow-up

Reactive focal mass drug administration (rfMDA)

About this trial

This is an interventional screening trial for Plasmodium Falciparum Malaria

Eligibility Criteria

18 Months - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for rfMDA:

Index cases: Presented as a confirmed malaria case to an intervention health facility or village malaria worker, and lives in a village within a selected intervention subdistrict, or worked or spent at least one night at a forest or forest-fringe site in the past 30 days located within an intervention subdistrict
Village residents: Lives in a village within a selected intervention subdistrict area and in one of the five households closest to the residence of an index case of malaria
Co-worker/traveler referral: Worked or traveled and spent at least one night in forest in past 30 days in same location within an intervention subdistrict as an index case of malaria
All participants: Willing and available to participate in the study and informed consent for participant under the age of 18 will be provided by the parent or guardian. Participants for focus group discussions (FGDs) and key informant interviews (KIIs); 18 years of age or older

Exclusion Criteria:

• For rfMDA:

Previous participation in the study as a result of any rfMDA event in the past 30 days
Individuals with severe disease or drug contra-indications will be excluded from the treatment component only
Artesunate-Mefloquine: Pregnancy in the first trimester, or known drug allergy
Use of Mefloquine within 60 days of first treatment prior to enrollment date.

Sites / Locations

Division of Vector Born Diseases, Ministry of HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

reactive focal mass drug administration (rfMDA)

Control

Arm Description

Reactive FMDA (rfMDA) led by VMVs in response to cases in study area sub-district, in both villages and forest workers; quantitative G6PD testing for all individuals and 14-day PQ for G6PD non-deficient.

Standard of care including case management through health facilities and malaria posts/VMVs; village-based RACD conducted by district staff in some areas.

Outcomes

Primary Outcome Measures

Confirmed P. falciparum and P. vivax malaria parasite incidence

Defined as the number of outpatient (OPD) malaria confirmed and suspected cases per person per year for each sub-district, as ascertained from the health facility registers, utilizing administrative catchment population size estimates for the exposure denominator.

PCR-based P. falciparum and P. vivax parasite prevalence in sampled sub-districts

Defined as the proportion of individuals ≥18 months old with P. falciparum or P. vivax infection (detected by PCR) out of all individuals ≥18 months tested within the end line survey.

Secondary Outcome Measures

Population coverage of rfMDA interventions

This indicator will be measured in two ways. Operational program coverage will be defined as the proportion of individuals ≥18 months old and households visited and offered the rfMDA interventions within the target areas per time period. Effective program coverage is defined as the proportion of individuals (≥18 months old) that agreed to participate in the rfMDA intervention among all individuals ≥18 months old eligible to participate in the intervention in the target population per time period.

Feasibility of conducting rfMDA at the community level

Feasibility will be determined based upon a combination of population coverage data, responses of provincial, district, and health staff, VMWs, and community members to interviews and focus groups at baseline and end line, village malaria workers (VMWs) competency checklists at baseline, midline, and end line, and cost data.

Acceptability of rfMDA approach

Acceptability will be determined based upon refusal rates during interventions and responses of community members and VMWs to end line questionnaire, interviews, and focus groups.

Adverse event rate

Safety measures will include the adverse event rate amongst treated individuals and hemoglobin measurement pre and post treatment for individuals receiving PQ.

Operational feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing and referral

Operational feasibility of G6PD testing and referral will be determined by responses of health staff and VMWs to interviews and focus groups at baseline and end line and competency checklists at baseline, midline, and end line, the proportion of P. vivax cases with a valid G6PD result, and proportion of referred cases presenting at a health facility for G6PD testing.

Assessment of P. vivax treatment adherence

Treatment adherence will be determined by the proportion of P. vivax cases with physical evidence of adherence through pill count and the P. vivax relapse rate across study arms.

Full Information

NCT ID

NCT05052502

First Posted

September 13, 2021

Last Updated

March 22, 2022

Sponsor

University of California, San Francisco

Collaborators

Center for Malariology, Parasitology, and Entomology, Tulane University School of Public Health and Tropical Medicine, University of Massachusetts, Amherst, Centers for Disease Control and Prevention

1. Study Identification

Unique Protocol Identification Number

NCT05052502

Brief Title

Targeting High Risk Populations With Enhanced Reactive Focal Mass Drug Administration in Thailand

Acronym

COMBAT

Official Title

Targeting High-risk Populations With Enhanced Reactive Focal Mass Drug Administration: A Study to Assess the Effectiveness and Feasibility for Plasmodium Falciparum and Plasmodium Vivax Malaria in Thailand

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2020 (Actual)

Primary Completion Date

March 31, 2022 (Anticipated)

Study Completion Date

March 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

Center for Malariology, Parasitology, and Entomology, Tulane University School of Public Health and Tropical Medicine, University of Massachusetts, Amherst, Centers for Disease Control and Prevention

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study assesses the effectiveness of reactive focal mass drug administration (rfMDA), targeting both village and forest working populations, compared to control for reducing the health promotion hospital-level (sub-district) incidence and prevalence of P. falciparum and P. vivax within five provinces in Thailand.

Detailed Description

Thailand currently has a well-developed and robust surveillance system based on detailed mapping of all cases to the village foci level and stratification of response. In fiscal year 2019, 5,833 cases of malaria were reported with 83.0% P. vivax and 12.9% P. falciparum; nine deaths were reported. This represents a 20.8% decrease in total cases from fiscal year 2018. Currently, there are 701 "A1" villages in 44 provinces. The research proposed here will evaluate the effectiveness and feasibility of enhanced reactive focal mass drug administration, results of which will have direct implications for continued roll out the community-led foci management, providing practical guidance that other malaria programs can utilize. Responding to the malaria among high risk populations is a requirement from the National Malaria Elimination Strategy in Thailand. Additionally, Thailand has experienced outbreaks related to forest work over the past several years, and consequently the Department of Vector Borne Disease (DVBD) is interested in introducing more aggressive parasite elimination strategies, including rfMDA for P. falciparum and P. vivax specifically targeting high-risk populations to interrupt transmission and rapidly accelerate elimination.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Plasmodium Falciparum Malaria, Plasmodium Vivax Malaria

7. Study Design

Primary Purpose

Screening

Study Phase

Not Applicable

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

49118 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

reactive focal mass drug administration (rfMDA)

Arm Type

Experimental

Arm Description

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Standard of care including case management through health facilities and malaria posts/VMVs; village-based RACD conducted by district staff in some areas.

Intervention Type

Other

Intervention Name(s)

Case Management and Follow-up

Intervention Description

Individuals will be told of their test result and a positive test result on either RDT will prompt treatment as per the national treatment guidelines. Individuals with P. falciparum infection will be treated with an age-appropriate course of dihydroartemisinin/piperaquine (DHAP) or artesunate-pyronaridine (Pyramax) and PQ. At all study sites in Thailand, patients with a P. vivax infection identified by the standard combination RDT will be tested by the VMV and Health Promotion Hospital (HPH) staff member using the quantitative G6PD RDT. G6PD normal individuals will be treated with Chloroquine (CQ) and a 14-day course of primaquine (PQ). G6PD deficient individuals will receive CQ alone and referred to the nearest health facility for further primaquine management decisions.

Intervention Type

Other

Intervention Name(s)

Reactive focal mass drug administration (rfMDA)

Intervention Description

Reactive focal mass administration (rfMDA) will be implemented around the index case household and to forest co-workers/co-travelers in Thailand. The VMV will conduct the investigation visit within 7 days after the notification of the index case. All members of the index case's household as well as all members of the nearest five households around the index case's household, including temporary visitors will be invited to participate in the study and to be treated for malaria without a malaria test. After obtaining participants' or parents/guardians' consent, the VMV will proceed with the participant questionnaire, and all consenting household members will be tested for G6PD using the G6PD quantitative test prior to administration of antimalarials. For rfMDA, all eligible participants will be offered artesunate-mefloquine (AS-MQ). Per national policy, a 14-day course of primaquine will be administered to G6PD non-deficient study participants.

Primary Outcome Measure Information:

Title

Confirmed P. falciparum and P. vivax malaria parasite incidence

Description

Time Frame

3 months

Title

PCR-based P. falciparum and P. vivax parasite prevalence in sampled sub-districts

Description

Defined as the proportion of individuals ≥18 months old with P. falciparum or P. vivax infection (detected by PCR) out of all individuals ≥18 months tested within the end line survey.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Population coverage of rfMDA interventions

Description

Time Frame

3 months

Title

Feasibility of conducting rfMDA at the community level

Description

Time Frame

3 months

Title

Acceptability of rfMDA approach

Description

Acceptability will be determined based upon refusal rates during interventions and responses of community members and VMWs to end line questionnaire, interviews, and focus groups.

Time Frame

3 months

Title

Adverse event rate

Description

Safety measures will include the adverse event rate amongst treated individuals and hemoglobin measurement pre and post treatment for individuals receiving PQ.

Time Frame

3 months

Title

Operational feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing and referral

Description

Time Frame

3 months

Title

Assessment of P. vivax treatment adherence

Description

Treatment adherence will be determined by the proportion of P. vivax cases with physical evidence of adherence through pill count and the P. vivax relapse rate across study arms.

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria for rfMDA: Index cases: Presented as a confirmed malaria case to an intervention health facility or village malaria worker, and lives in a village within a selected intervention subdistrict, or worked or spent at least one night at a forest or forest-fringe site in the past 30 days located within an intervention subdistrict Village residents: Lives in a village within a selected intervention subdistrict area and in one of the five households closest to the residence of an index case of malaria Co-worker/traveler referral: Worked or traveled and spent at least one night in forest in past 30 days in same location within an intervention subdistrict as an index case of malaria All participants: Willing and available to participate in the study and informed consent for participant under the age of 18 will be provided by the parent or guardian. Participants for focus group discussions (FGDs) and key informant interviews (KIIs); 18 years of age or older Exclusion Criteria: • For rfMDA: Previous participation in the study as a result of any rfMDA event in the past 30 days Individuals with severe disease or drug contra-indications will be excluded from the treatment component only Artesunate-Mefloquine: Pregnancy in the first trimester, or known drug allergy Use of Mefloquine within 60 days of first treatment prior to enrollment date.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Adam Bennett, MA, PhD

Phone

1-415-476-5590

adam.bennett@ucsf.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adam Bennett, MA, PhD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Cheewanan Lertpiriyasuwat, MD

Organizational Affiliation

Department of Disease Control, Ministry of Public Health Thailand

Official's Role

Principal Investigator

Facility Information:

Facility Name

Division of Vector Born Diseases, Ministry of Health

City

Bangkok

Country

Thailand

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Prayuth Sudathip, DrPH

Phone

02-590-3106-7

psudathip@gmail.com

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data will not be shared with any parties outside of the study team.

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Targeting High Risk Populations With Enhanced Reactive Focal Mass Drug Administration in Thailand

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