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

Plasmodium Falciparum Malaria Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05052502
• Other study ID #: 19-04062020
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: March 2022
• Source: University of California, San Francisco
• Contact: Adam Bennett, MA, PhD
• Phone: 1-415-476-5590
• Email: adam.bennett[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49118
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Malaria, Vivax
• Plasmodium Falciparum Malaria
• Plasmodium Vivax Malaria

Intervention

Other:
• Case Management and Follow-up
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.
• Reactive focal mass drug administration (rfMDA)
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.

Locations

Country	Name	City	State
Thailand	Division of Vector Born Diseases, Ministry of Health	Bangkok

Sponsors (5)

Lead Sponsor	Collaborator
University of California, San Francisco	Center for Malariology, Parasitology, and Entomology, Centers for Disease Control and Prevention, Tulane University School of Public Health and Tropical Medicine, University of Massachusetts, Amherst

Country where clinical trial is conducted

Thailand, 

References & Publications (19)

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 months
Primary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months