AzTrials
AzTrials

Plasmodium Falciparum MalariaPhase 4NCT03783299

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

A Phase 4 study testing Standard RDT and HS-RDT, Artemether-lumefantrine and Primaquine Phosphate in people with Plasmodium Falciparum Malaria, run by University of California, San Francisco at 1 site in Laos.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 months and olderHealthy volunteers can take part
Conditions the study is for
Plasmodium Falciparum Malaria
What is being tested?
Standard RDT and HS-RDT, Artemether-lumefantrine and Primaquine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39,968 participants
Where
1 siteLaos
Study dates
28 Nov 2017to 31 Dec 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 months and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Laos1 site

  • Centre for Marialogy, Parasitology, and Entomology

    Vientiane

Other trials in Laos

About this study

Official title: Assessing the Effectiveness of Targeted Active Case Detection Among High Risk Populations in Southern Lao PDR

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.

Read the detailed description

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.

Being tested
Standard RDT and HS-RDT, Artemether-lumefantrine, Primaquine Phosphate
Medical subject headings
Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard RDT and HS-RDTDiagnostic test

    Also called SD Bioline Alere Malaria Ag Pf High Sensitive Cat #05FK140, SD Bioline Pf/Pv 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)

  • Standard RDT and HS-RDTDiagnostic test

    Also called SD Bioline Alere Malaria Ag Pf High Sensitive Cat #05FK140, SD Bioline Pf/Pv 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.

  • Artemether-lumefantrineDrug

    Also called Coartem

    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 PhosphateDrug

    Also called Primaquine

    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.

Study groups in NCT03783299
Study groupRoleWhat they receive
Village-based MTATExperimentalIntervention: 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)
Receives: Diagnostic Test: Standard RDT and HS-RDT; Drug: Artemether-lumefantrine; Drug: Primaquine Phosphate
Peer navigator-led FTATExperimentalIntervention: 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)
Receives: Diagnostic Test: Standard RDT and HS-RDT; Drug: Artemether-lumefantrine; Drug: Primaquine Phosphate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Community-level PCR-based P. falciparum prevalence in sampled villages

    This is defined as the proportion of individuals >18 months old with P. falciparum infection (detected by PCR) out of all individuals >18 months tested within the 2017 and 2018 surveys.The effectiveness of the interventions will be assessed as P. falciparum prevalence via PCR at end-line (post only) using generalized linear mixed effects models with separate random intercepts to allow for clustering within villages and health center catchments. The binomial distribution will be used to analyze prevalence outcomes (logistic regression)

    Measured: 4 months

  2. HS-RDT-based test positivity rate in village-based and forest-based samples

    This is defined as the proportion of all individuals tested by HS-RDT at each round of the MTAT interventions or during routine FTAT, with a positive HS-RDT, among the population older than 18 months.The HS-RDT and RDT test positivity rates will be estimated for the MTAT villages during each intervention round. This will be done as soon as data on RDT and HS-RDT results are available, which would be expected to be one month following each round. Differences in prevalence measures at each round will be assessed using a χ2 test, as well as logistic regression models to account for potential confounding factors.

    Measured: 6 months

  3. Village-based population coverage of test and treat interventions

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

    Measured: 3 months

  4. Community-level confirmed P. falciparum malaria parasite incidence

    This is defined as the number of total and confirmed outpatient (OPD) malaria confirmed and suspected cases per person per year for each village, as ascertained from the health facility registers, utilizing village population size estimates for the exposure denominator. Data pertaining to this outcome will be analyzed on an intention-to-treat basis. Monthly counts of confirmed malaria cases from the health facility registers will be linked to villages and analyzed in a time series Poisson or negative binomial model with random intercepts at the health center catchment and village levels.

    Measured: 1 year

Secondary outcomes (3)

  1. Serology

    Seropositivity to a panel of standard malaria parasite antigens for P. falciparum and P. vivax (including merozoite surface protein-1 (MSP-1) and apical membrane antigen-1 (AMA-1), will be used to examine both recent and medium-term exposures. These data will also be mapped used captured global positioning system (GPS) coordinates to examine serological hotspots. Finally, novel antigens will also be used to further explore any differences in parasite exposure between study arms. Vector exposure may also be explored using antigens to anopheline salivary proteins.

    Measured: 2 months

  2. Cost and cost effectiveness

    For the costing portion of the study, the cost per case investigation conducted, cost per additional positive case identified using FTAT in village- and forest-based HRPs, and the cost per case actively detected per person screened during screen and treat. The cost-effectiveness of screen and treat will also be compared between village-based activities and peer-navigator led testing.

    Measured: 12 months

  3. Sensitivity and specificity of HS-RDTs

    The P. falciparum prevalence from all individuals tested with HS-RDTs will be compared with parallel results from standard RDTs (all field testing activities) and to subsequent PCR-based testing (cross-sectional survey, FTAT and MTAT subset). In the latter case, the PCR-based result will serve as the gold standard for all comparisons. Sensitivity and specificity and receiver operating curve (ROC) analyses will be conducted to assess the performance of the HS-RDTs in field situations, and in the presence of mixed-species infections. DBS will be collected for cross-sectional survey, FTAT and MTAT.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2018
  2. Study start28 Nov 2017
  3. Primary completion30 Nov 2018
  4. Study completion31 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Screening
Allocation
Randomised
Intervention model
Factorial
Model description
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).
Masking
None (open label)
Enrolment
39,968 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03783299
Sponsor's protocol ID
17-22577
Other IDs
A124497
Status last verified
Feb 2021
First submitted
30 Nov 2018
Last updated
23 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual participant data will not be shared with any parties outside of the study team.

Publications

  • 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.

    PubMed 23442748

  • 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.

    PubMed 23815811

  • 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.

    PubMed 25429102

  • 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.

    PubMed 26931488

  • 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.

    PubMed 27887652

  • 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.

    PubMed 23049687

  • 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.

    PubMed 23594387

  • 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

  • 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

  • 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.

  • 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.

    PubMed 32118199

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Standard RDT and HS-RDT, Artemether-lumefantrine and Primaquine Phosphate in people with Plasmodium Falciparum Malaria, run by University of California, San Francisco at 1 site in Laos.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Laos. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Community-level PCR-based P. falciparum prevalence in sampled villages (time frame: 4 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03783299, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in