Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05052502
Other study ID # 19-04062020
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
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
Health authority
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.

Study Design


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)

Baum E, Sattabongkot J, Sirichaisinthop J, Kiattibutr K, Davies DH, Jain A, Lo E, Lee MC, Randall AZ, Molina DM, Liang X, Cui L, Felgner PL, Yan G. Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax infections are common in western Thailand - molecular and serological evidence. Malar J. 2015 Feb 25;14:95. doi: 10.1186/s12936-015-0611-9. — View Citation

Beutler E, Duparc S; G6PD Deficiency Working Group. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg. 2007 Oct;77(4):779-89. Review. — View Citation

Bousema T, Griffin JT, Sauerwein RW, Smith DL, Churcher TS, Takken W, Ghani A, Drakeley C, Gosling R. Hitting hotspots: spatial targeting of malaria for control and elimination. PLoS Med. 2012 Jan;9(1):e1001165. doi: 10.1371/journal.pmed.1001165. Epub 2012 Jan 31. — View Citation

Campbell MK, Piaggio G, Elbourne DR, Altman DG; CONSORT Group. Consort 2010 statement: extension to cluster randomised trials. BMJ. 2012 Sep 4;345:e5661. doi: 10.1136/bmj.e5661. — View Citation

Center for Malariology Parasitology and Entomology Lao PDR. Lao PDR Malaria National Strategic Plan 2016-2020. (2015).

Chan CW, Sakihama N, Tachibana S, Idris ZM, Lum JK, Tanabe K, Kaneko A. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies. PLoS One. 2015 Mar 20;10(3):e0119475. doi: 10.1371/journal.pone.0119475. eCollection 2015. — View Citation

Corran P, Coleman P, Riley E, Drakeley C. Serology: a robust indicator of malaria transmission intensity? Trends Parasitol. 2007 Dec;23(12):575-82. Epub 2007 Nov 7. Review. — View Citation

Cotter C, Sturrock HJ, Hsiang MS, Liu J, Phillips AA, Hwang J, Gueye CS, Fullman N, Gosling RD, Feachem RG. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013 Sep 7;382(9895):900-11. doi: 10.1016/S0140-6736(13)60310-4. Epub 2013 Apr 15. Review. Erratum in: Lancet. 2013 Sep 7;382(9895):858. — View Citation

Das S, Peck RB, Barney R, Jang IK, Kahn M, Zhu M, Domingo GJ. Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples. Malar J. 2018 Mar 17;17(1):118. doi: 10.1186/s12936-018-2268-7. Erratum in: Malar J. 2019 Feb 4;18(1):33. — View Citation

Douglas NM, Poespoprodjo JR, Patriani D, Malloy MJ, Kenangalem E, Sugiarto P, Simpson JA, Soenarto Y, Anstey NM, Price RN. Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study. PLoS Med. 2017 Aug 29;14(8):e1002379. doi: 10.1371/journal.pmed.1002379. eCollection 2017 Aug. — View Citation

Howes RE, Dewi M, Piel FB, Monteiro WM, Battle KE, Messina JP, Sakuntabhai A, Satyagraha AW, Williams TN, Baird JK, Hay SI. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J. 2013 Nov 15;12:418. doi: 10.1186/1475-2875-12-418. — View Citation

Hustedt J, Canavati SE, Rang C, Ashton RA, Khim N, Berne L, Kim S, Sovannaroth S, Ly P, Ménard D, Cox J, Meek S, Roca-Feltrer A. Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting. Malar J. 2016 Mar 1;15:132. doi: 10.1186/s12936-016-1191-z. — View Citation

Landier J, Parker DM, Thu AM, Lwin KM, Delmas G, Nosten FH; Malaria Elimination Task Force Group. Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme. Lancet. 2018 May 12;391(10133):1916-1926. doi: 10.1016/S0140-6736(18)30792-X. Epub 2018 Apr 24. — View Citation

Ministry of Health Lao PDR. The Evaluation of G6PD Rapid Tests and the Use of Primaquine for the Treatment of Plasmodium Vivax Infections in Luangprabang, Savannakhet and Champasak Provinces (Apr-Nov 2015). (2015)

Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, Abeyasinghe RR, Rodriguez MH, Maharaj R, Tanner M, Targett G. Operational strategies to achieve and maintain malaria elimination. Lancet. 2010 Nov 6;376(9752):1592-603. doi: 10.1016/S0140-6736(10)61269-X. Epub 2010 Oct 28. Review. — View Citation

Rossi G, Van den Bergh R, Nguon C, Debackere M, Vernaeve L, Khim N, Kim S, Menard D, De Smet M, Kindermans JM. Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia. Clin Infect Dis. 2018 Jan 6;66(2):296-298. doi: 10.1093/cid/cix781. — View Citation

White MT, Karl S, Battle KE, Hay SI, Mueller I, Ghani AC. Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission. Elife. 2014 Nov 18;3. doi: 10.7554/eLife.04692. — View Citation

WHO. Updated WHO policy recommendation: Single dose primaquine as a gametocytocide in Plasmodium falciparum malaria. World Health Organisation (2012).

World Health Organization. (2015). Guidelines for the treatment of malaria. World Health Organization

* Note: There are 19 references in allClick 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
See also
  Status Clinical Trial Phase
Completed NCT04577066 - Safety and Preliminary Protective Efficacy of Genetically Attenuated GA2 Parasites. Phase 1/Phase 2
Completed NCT01883609 - A Safety and Efficacy Study of ChAd63/MVA METRAP + RTS,S Phase 1/Phase 2
Completed NCT00593398 - Malarial Immunity in Pregnant Cameroonian Women
Completed NCT01659281 - Efficacy of Artesunate-Mefloquine Combination Therapy in Trat Province, Thailand N/A
Completed NCT00074841 - Trial of Azithromycin Plus Chloroquine Versus Sulfadoxine-Pyrimethamine Plus Chloroquine for the Treatment of Uncomplicated Malaria in India Phase 2/Phase 3
Recruiting NCT04416945 - Targeting High Risk Populations With Enhanced Reactive Case Detection in Southern Lao Peoples Democratic Republic N/A
Completed NCT00314899 - Fetal Immunity to Falciparum Malaria
Completed NCT02867059 - SJ733 Induced Blood Stage Malaria Challenge Study Phase 1
Completed NCT00701961 - Pharmacokinetic of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnancy Phase 2/Phase 3
Completed NCT00338520 - Hyperphenylalaninemia in Cerebral Malaria N/A
Completed NCT00707200 - The Cytoadherence in Pediatric Malaria (CPM) Study N/A
Completed NCT00393757 - Malaria Transmission and Immunity in Highland Kenya
Completed NCT03783299 - Targeted Active Case Detection Among High Risk Populations in Southern Lao Peoples Democratic Republic Phase 4
Completed NCT02614404 - Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria Phase 1
Completed NCT00358332 - Phase I Pediatric FMP2.1/AS02A Trial in Mali Phase 1
Completed NCT00730782 - Assessment of Three Formulations of the Candidate Vaccine AMA 1 in Healthy Dutch Adult Volunteers Phase 1
Completed NCT00349713 - FMP2.1 Trial in Bandiagara, Mali Phase 1
Completed NCT04093765 - Mass Screening and Treatment for Reduction of Falciparum Malaria N/A
Completed NCT03764527 - Tolerability and Efficacy of Artemether-Lumefantrine Versus Artesunate + Amodiaquine in Zanzibar Phase 4
Completed NCT03773536 - Efficacy and Safety of Artesunate + Amodiaquine With SLD of Primaquine for Treatment of Falciparum Malaria in Zanzibar Phase 4