Targeted Active Case Detection Among High Risk Populations in Southern Lao Peoples Democratic Republic

NCT ID: NCT03783299

Last Updated: 2021-02-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

39968 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-28

Study Completion Date

2018-12-31

Brief Summary

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This study assesses the effectiveness of targeted active case detection among high-risk populations in Southern Lao Peoples Democratic Republic (PDR). The investigators hypothesize that active case detection using the next generation of HRP-2 rapid diagnostic tests (RDTs) can help bridge gaps in identification of high-risk asymptomatic individuals with low density parasitemia, allowing for targeting of this reservoir and thereby reducing transmission. The investigators hypothesize that active case detection (testing and treating positive cases) with these RDTs will lead to a reduction in P. falciparum transmission.

Detailed Description

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This study is the second phase of work in Champasak Province, Southern Lao PDR, building off a formative phase of work that characterized the demographics, occupations, migratory patterns, health-seeking behaviors, and social networks of mobile and migrant populations (MMPs) in four target districts. This phase of the study now aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of proactive targeted test-and-treat activities using high-sensitivity malaria rapid diagnostic tests (HS-RDTs) for reducing Plasmodium falciparum malaria transmission in Champasak Province among (1) village residents and (2) mobile and migrant populations (MMPs) and other high-risk populations (HRPs).

The study will specifically assess the role of HS-RDTs, a diagnostic test that offers potentially \~10-fold greater sensitivity than standard RDTs, in active case detection at both the village-level and in forest-going HRPs for decreasing prevalence and incidence of P. falciparum in target areas. The effectiveness of these interventions will be compared independently and in combination against areas with no study interventions (standard of care) over the course of implementation (planned for October 2017 - November 2018).

The two main study interventions are mass test and treat (MTAT) using HS-RDTs in village-based populations, and peer navigator (PN) led focal test and treat (FTAT) using HS-RDTs in forest based HRPs. Primary outcomes will include PCR-based P. falciparum prevalence at endline. Following a baseline cross-sectional survey in November-December 2017, the interventions will consist of 3 rounds of MTAT spaced throughout the year, with potential to reduce to 2 based upon initial prevalence estimates, and ongoing FTAT by PNs among forest and forest-fringe HRPs, with the primary evaluation to be conducted through an end-line cross-sectional survey in November 2018.

Conditions

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Plasmodium Falciparum Malaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

The study is employing a split-plot community-randomized controlled trial design, with peer navigator test and treat randomized at the health center catchment level, and village-based test and treat randomized at the village level within health center catchment areas (HCCA).
Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Village-based MTAT

Intervention: For all households in intervention villages, after obtaining informed consent, MTAT will be conducted with all household members aged 18 months and older.

The MTAT team will test each individual using both a standard RDT and HS-RDTs. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ)

Group Type EXPERIMENTAL

Standard RDT and HS-RDT

Intervention Type DIAGNOSTIC_TEST

All household members (residents and temporary visitors) aged 18 months and older will be invited to participate in an RDT and blood collection component. After consenting, the MTAT team will capture axillary temperature, and test each individual using both a standard RDT (SD Bioline Pf/Pv RDT) and HS-RDT (SD Bioline Malaria Ag P.f High Sensitive Cat# 05FK140)

Artemether-lumefantrine

Intervention Type DRUG

If found positive by standard RDT or HS-RDT, treatment will be administered, and women of reproductive age will be assessed as outlined in the protocol. All individuals who have provided informed consent, test positive by either HS-RDT or standard RDT, are ≥18 months old, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages) and SLD-PQ according to national treatment guidelines.

Primaquine Phosphate

Intervention Type DRUG

If found positive by standard RDT or HS-RDT, treatment will be administered, and women of reproductive age will be assessed as outlined in the protocol. All individuals who have provided informed consent, test positive by either HS-RDT or standard RDT, are ≥18 months old, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages) and SLD-PQ according to national treatment guidelines.

Peer navigator-led FTAT

Intervention: Peer navigators will actively seek non-village based HRPs in forested areas, rice fields and plantations, and any other non-permanent settlements within target health center catchment areas, and conduct FTAT among all consenting individuals.

The Peer Navigators will test each individual using both a standard RDT and HS-RDT. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ)

Group Type EXPERIMENTAL

Standard RDT and HS-RDT

Intervention Type DIAGNOSTIC_TEST

All individuals will be invited to participate in an RDT and blood collection component. Informed consent will be obtained from all participants. After consenting, the PNs will capture axillary temperature, and test each individual using both a standard RDT (SD Bioline Pf/Pv RDT) and HS-RDT (SD Bioline Alere Malaria Ag Pf High Sensitive Cat #05FK140). Dried blood spots (DBS) will also be collected on all HRPs if deemed feasible.

Artemether-lumefantrine

Intervention Type DRUG

If found positive by standard RDT or HS-RDT, treatment will be administered, and women of reproductive age will be assessed as outlined in the protocol. All individuals who have provided informed consent, test positive by either HS-RDT or standard RDT, are ≥18 months old, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages) and SLD-PQ according to national treatment guidelines.

Primaquine Phosphate

Intervention Type DRUG

If found positive by standard RDT or HS-RDT, treatment will be administered, and women of reproductive age will be assessed as outlined in the protocol. All individuals who have provided informed consent, test positive by either HS-RDT or standard RDT, are ≥18 months old, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages) and SLD-PQ according to national treatment guidelines.

Interventions

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Standard RDT and HS-RDT

All household members (residents and temporary visitors) aged 18 months and older will be invited to participate in an RDT and blood collection component. After consenting, the MTAT team will capture axillary temperature, and test each individual using both a standard RDT (SD Bioline Pf/Pv RDT) and HS-RDT (SD Bioline Malaria Ag P.f High Sensitive Cat# 05FK140)

Intervention Type DIAGNOSTIC_TEST

Standard RDT and HS-RDT

All individuals will be invited to participate in an RDT and blood collection component. Informed consent will be obtained from all participants. After consenting, the PNs will capture axillary temperature, and test each individual using both a standard RDT (SD Bioline Pf/Pv RDT) and HS-RDT (SD Bioline Alere Malaria Ag Pf High Sensitive Cat #05FK140). Dried blood spots (DBS) will also be collected on all HRPs if deemed feasible.

Intervention Type DIAGNOSTIC_TEST

Artemether-lumefantrine

If found positive by standard RDT or HS-RDT, treatment will be administered, and women of reproductive age will be assessed as outlined in the protocol. All individuals who have provided informed consent, test positive by either HS-RDT or standard RDT, are ≥18 months old, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages) and SLD-PQ according to national treatment guidelines.

Intervention Type DRUG

Primaquine Phosphate

If found positive by standard RDT or HS-RDT, treatment will be administered, and women of reproductive age will be assessed as outlined in the protocol. All individuals who have provided informed consent, test positive by either HS-RDT or standard RDT, are ≥18 months old, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages) and SLD-PQ according to national treatment guidelines.

Intervention Type DRUG

Other Intervention Names

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SD Bioline Alere Malaria Ag Pf High Sensitive Cat #05FK140 SD Bioline Pf/Pv RDT SD Bioline Alere Malaria Ag Pf High Sensitive Cat #05FK140 SD Bioline Pf/Pv RDT Coartem Primaquine

Eligibility Criteria

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Inclusion Criteria

* All household members 18 months of age and older.
* Study participants include those in the 14 selected health center catchment areas within the four target districts in Champasak Province, Southern Lao PDR; Moulapamook, Panthampone, Sanamsaboun, and Soukhuma.
* Members of households who have provided informed consent will be included for blood samples collection and treatment for identified malaria cases if meeting the appropriate criteria.


* All persons 15 years and older who have spent at least one night outside a formal village in the past one month.
* Individuals must be 18 years and older and willing and able to provide consent to be included in the peer navigator or study staff focus group discussions and key informant interviews
* Study participants include those in the 14 selected health center catchment areas within the four target districts in Champasak Province, Southern Lao PDR; Moulapamook, Panthampone, Sanamsaboun, and Soukhuma
* High-risk populations in forested areas, rice field regions, plantations and any informal settlements
* Individuals travelling into the HCCA who are willing and sufficiently able to communicate with PNs to assess their eligibility

Exclusion Criteria

* Household members less than 18 months of age will be excluded.
* Any individuals under the age of 18 months will be excluded from RDT testing and blood collection.

Peer Naviagtor-Led FTAT


\- Individuals under the age of 18 will be excluded from peer navigator or study staff focus group discussions and key informant interviews.
Minimum Eligible Age

18 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Center for Malariology, Parasitology, and Entomology

UNKNOWN

Sponsor Role collaborator

The National Institute of Public Health

UNKNOWN

Sponsor Role collaborator

Health Poverty Action

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adam Bennett, MA, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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Centre for Marialogy, Parasitology, and Entomology

Vientiane, , Laos

Site Status

Countries

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Laos

References

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Tiono AB, Ouedraogo A, Ogutu B, Diarra A, Coulibaly S, Gansane A, Sirima SB, O'Neil G, Mukhopadhyay A, Hamed K. A controlled, parallel, cluster-randomized trial of community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso. Malar J. 2013 Feb 27;12:79. doi: 10.1186/1475-2875-12-79.

Reference Type BACKGROUND
PMID: 23442748 (View on PubMed)

Mosha JF, Sturrock HJ, Greenhouse B, Greenwood B, Sutherland CJ, Gadalla N, Atwal S, Drakeley C, Kibiki G, Bousema T, Chandramohan D, Gosling R. Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics. Malar J. 2013 Jul 1;12:221. doi: 10.1186/1475-2875-12-221.

Reference Type BACKGROUND
PMID: 23815811 (View on PubMed)

Cook J, Xu W, Msellem M, Vonk M, Bergstrom B, Gosling R, Al-Mafazy AW, McElroy P, Molteni F, Abass AK, Garimo I, Ramsan M, Ali A, Martensson A, Bjorkman A. Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar. J Infect Dis. 2015 May 1;211(9):1476-83. doi: 10.1093/infdis/jiu655. Epub 2014 Nov 26.

Reference Type BACKGROUND
PMID: 25429102 (View on PubMed)

Hustedt J, Canavati SE, Rang C, Ashton RA, Khim N, Berne L, Kim S, Sovannaroth S, Ly P, Menard 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.

Reference Type BACKGROUND
PMID: 26931488 (View on PubMed)

Parker DM, Landier J, von Seidlein L, Dondorp A, White L, Hanboonkunupakarn B, Maude RJ, Nosten FH. Limitations of malaria reactive case detection in an area of low and unstable transmission on the Myanmar-Thailand border. Malar J. 2016 Nov 25;15(1):571. doi: 10.1186/s12936-016-1631-9.

Reference Type BACKGROUND
PMID: 27887652 (View on PubMed)

Hoyer S, Nguon S, Kim S, Habib N, Khim N, Sum S, Christophel EM, Bjorge S, Thomson A, Kheng S, Chea N, Yok S, Top S, Ros S, Sophal U, Thompson MM, Mellor S, Ariey F, Witkowski B, Yeang C, Yeung S, Duong S, Newman RD, Menard D. Focused Screening and Treatment (FSAT): a PCR-based strategy to detect malaria parasite carriers and contain drug resistant P. falciparum, Pailin, Cambodia. PLoS One. 2012;7(10):e45797. doi: 10.1371/journal.pone.0045797. Epub 2012 Oct 1.

Reference Type BACKGROUND
PMID: 23049687 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23594387 (View on PubMed)

World Health Organization. Strategy for malaria elimination in the Greater Mekong Subregion: 2015-2030 [Internet]. Geneva: Global Malaria Program, WHO; 2015. Available: http://iris.wpro.who.int/bitstream/handle/10665.1/10945/9789290617181_eng.pdf

Reference Type BACKGROUND

World Health Organization Regional Office for South-East Asia (SEARO). Approaches for mobile and migrant populations in the context of malaria multi-drug resistance and malaria elimination in the Greater Mekong Subregion [Internet]. Thailand; 2016. Available: http://apps.who.int/iris/bitstream/10665/204351/2/Approaches_%20mobile_migrant_populations.pdf

Reference Type BACKGROUND

Center for Malariology, Parasitology, and Entomology, Lao PDR. Lao PDR Malaria National Strategic Plan 2016-2020. Vientiane, Lao PDR: Ministry of Health, Lao PDR; 2015.

Reference Type BACKGROUND

Lover AA, Dantzer E, Hocini S, Estera R, Rerolle F, Smith JL, Hwang J, Gosling R, Yukich J, Greenhouse B, Jacobson J, Phetsouvanh R, Hongvanthong B, Bennett A. Study protocol for a cluster-randomized split-plot design trial to assess the effectiveness of targeted active malaria case detection among high-risk populations in Southern Lao PDR (the AcME-Lao study). Gates Open Res. 2019 Dec 17;3:1730. doi: 10.12688/gatesopenres.13088.1. eCollection 2019.

Reference Type DERIVED
PMID: 32118199 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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A124497

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

17-22577

Identifier Type: -

Identifier Source: org_study_id

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