Yersinia Pestis Lateral Flow Immunoassay for Blood Samples (SMARTPRT)

December 12, 2022 updated by: Brimrose Technology Corporation

Point of Care Diagnostic to Identify the Causative Agent of the Plague in Blood Samples

Plague is a deadly but highly treatable disease caused by the bacterium Y. pestis. Due to the historical development of Y. pestis as a bioweapon by several nation states, it is listed by the US as a potential bioweapon that could be used against US warfighters. Although this bacterium is ecologically established worldwide, it mostly affects impoverished people who live in rural low-resource areas of Madagascar. Plague is acquired directly from bites of infected fleas but, if left untreated, it can progress to the highly lethal pneumonic form that can result in human to human transmission. With the dangers of pneumonic plague in the context of both natural outbreak and as a bioweapon used against warfighter, the goal of this study is to investigate a diagnostic test that is able to rapidly and locally diagnose this disease in low-resource settings. This study aims to evaluate a US-developed new LFI (Lateral Flow Immunoassay) assay intended for capillary blood (finger-prick) to diagnose humans infected with Y. pestis. The investigators will rigorously validate with assay on human populations from active plague sites and correlate the results with the results of paired clinical samples used in standard medical workup using existing diagnostics tests.

Study Overview

Detailed Description

The purpose of this study will be to generate the data required to thoroughly validate the ability of plague LFI assay (Lateral Flow Immunoassay) to accurately diagnose human infections with Y. pestis. These validation data will eventually be presented to US Food and Drug Administration (FDA; along with data from other studies that NAU will not participate) to seek approval for commercial license. The objective will be to validate this assay on the capillary blood of humans suspected to have plague as well as a study cohort likely to not have plague. From the suspected population; the specific aims of this study are to enroll up to 300 participants who present clinical signs of illness based on specific inclusion criteria. We will collect two types of blood samples from enrolled participants 1) capillary blood from a finger prick and 2) venous blood. The capillary blood will be used for direct testing on the LFI assay and the venous blood will be used to perform independent validations. This study is designed as a correlation study to understand 1) how LFI assay results compare with results from traditional diagnostic methods based on DNA detection methods and bacterial culture isolate on bubo aspirate or sputum and 2) effectiveness of capillary blood to serve as a diagnostic clinical sample as compared with traditional biological samples (venous blood, bubo and sputum). The study is designed to evaluate the outcome of LFI and how LFI results correlate with the standard plague diagnostics methods used in Madagascar and other methods. We are not examining the relationship between the results of the LFI and health outcomes of the participants. Decision of participant's medical treatment is solely based on the clinical judgment of the physician and guidelines set forth by Madagascar National Plague Control Program (PNLP); no formal test is involved with medical decision. All participants who are tested by LFI will have received medical treatment prior to the start of the study and the continuation of their medical treatment is guided by PNLP and physician judgment only. Again, we are not looking at the relationship between the results of the LFI and health outcomes of the participants.

From the non-suspect cohort, greater detail will be provided as obtained. In brief, this subject population will consist of active duty US Naval personnel and DoD beneficiaries presenting to participating study sites in the United States with influenza-like symptoms (fever, cough, sore throat). Since the US is non-endemic for plague, all participants will be presumed to be negative for Y. pestis.

Study Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Analamanga
      • Antananarivo, Analamanga, Madagascar, 101
        • Recruiting
        • Institut Pasteur de Madagascar
        • Contact:
          • Voahangy Andrianaivoarimanana, Ph.D.
          • Phone Number: 00261340654145
          • Email: kekely@pasteur.mg
        • Contact:
          • Minoarisoa RAJERISON, Ph.D>
          • Phone Number: 00261341983916
          • Email: mino@pasteur.mg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 73 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Malagasy Participants. Subjects will be recruited at rural health centers throughout Madagascar. Participants will be comprised of rural people with symptoms consistent with plague. The Madagascar Ministry of Public Health requires declaration of all suspected human plague cases and collection of biological samples (sputum and/or bubo aspirates) from these cases for medical workup for confirmation.

USN Health Center Participants. The subject population will consist of active duty US Naval personnel and DoD beneficiaries presenting to participating study sites in the United States with influenza-like symptoms (fever, cough, sore throat). Since the US is non-endemic for plague, all participants will be presumed to be negative for Y. pestis.

Description

Inclusion criteria - Malagasy Participants

  1. Adults 18 to 75 years old (male and female): Able to receive and give verbal communication.
  2. Children 5 to 17 years old (vulnerable population): Parents or legal guardian must be available to give permission. Parents or legal guardian to consent for children (5-6 years).
  3. Suspected human plague case by local medical professional. Include at least one of the following: For bubonic plague: high fever, chills, and/or presence of painful bubo; For pneumonic plague: high fever, chills, cough for less than 5 days, bloody sputum, and/or chest pains; patients may be recruited from both plague surveillance program and non-plague surveillance programs.

Exclusion criteria - Malagasy Participants

  1. Children under the age of 5 years old
  2. Children between the age of 5 years to 17 years without a parent or legal guardian
  3. Not compliant with the study procedure (blood sampling)

Inclusion criteria - USN Health Center Participants

  1. Active duty personnel and DoD beneficiaries that present to participating study sites with influenza-like-illness (fever, cough, sore throat).
  2. Age range >=13 to 75 y.o.
  3. Able to receive/give consent (or assent if <18 y.o.) 4, Presenting with influenza-like-illness (fever of 100.5 F or higher, cough and/or sore throat)

5. USN Special Categories: Minors/children (45CFR Subpt. D/DoDI 3216.02, Encl 3, Para 7d); Students; Active duty military personnel (3216.02, Encl.3 Para. 7.e); Economically disadvantaged persons (32CFR 219.11(b); Educationally disadvantaged persons (32CFR 219.11(b).

Exclusion criteria - USN Health Center Participants

  1. <13 y.o.
  2. Unable to give written consent (if under 18)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Malagasy Participants
Malagasy Participants. Subjects will be recruited at rural health centers throughout Madagascar. Participants will be comprised of rural people with symptoms consistent with plague. The Madagascar Ministry of Public Health requires declaration of all suspected human plague cases and collection of biological samples (sputum and/or bubo aspirates) from these cases for medical workup for confirmation.
A dipstick type of rapid test for antigens of the plague bacterium Yersinia pestis in samples from enrolled participants from both a known geography of plague activity (Madagascar) as well as samples from a geographically separated population of likely plague free status (US Naval Health Research Center, San Diego, CA).
Other Names:
  • PRT
  • Lateral Flow Immunoassay for the Plague
  • SMART Plague Rapid Test
  • SMARTPRT
  • Plague LFI for F1 and LcrV antigens of Y. pestis
  • Lateral Flow Immunoassay for Yersinia pestis
  • LFI
USN Health Research Center
USN Health Center Participants. The subject population will consist of active duty US Naval personnel and DoD beneficiaries presenting to participating study sites in the United States with influenza-like symptoms (fever, cough, sore throat). Since the US is non-endemic for plague, all participants will be presumed to be negative for Y. pestis.
A dipstick type of rapid test for antigens of the plague bacterium Yersinia pestis in samples from enrolled participants from both a known geography of plague activity (Madagascar) as well as samples from a geographically separated population of likely plague free status (US Naval Health Research Center, San Diego, CA).
Other Names:
  • PRT
  • Lateral Flow Immunoassay for the Plague
  • SMART Plague Rapid Test
  • SMARTPRT
  • Plague LFI for F1 and LcrV antigens of Y. pestis
  • Lateral Flow Immunoassay for Yersinia pestis
  • LFI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LFI results on finger-prick blood correlate with the results of standard WHO-approved diagnostic tests for plague
Time Frame: Up to 3 weeks post sample collection and processing of each participant.

Description: Standard WHO-approved diagnostic testing uses bubo aspirates or sputum as clinical matrices to perform the following tests: F1RDT, qPCR analysis, and culture.

WHO defines a confirmatory positive plague case when the bubo or sputum is positive on F1RDT and positive on either qPCR or culture.

Up to 3 weeks post sample collection and processing of each participant.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LFI results on finger-prick blood correlate with LFI results from bubo aspirate or sputum clinical matrices.
Time Frame: Up to 3 weeks post sample collection and processing of each participant.

Standard WHO-approved diagnostic testing uses bubo aspirates or sputum as clinical matrices to perform the following tests: F1RDT, qPCR analysis, and culture.

WHO defines a confirmatory positive plague case when the bubo or sputum is positive on F1RDT and positive on either qPCR or culture.

Up to 3 weeks post sample collection and processing of each participant.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
LFI results on finger-prick blood correlate with the test results on venous blood using the following diagnostic methods: LFI, qPCR, ELISA and FilmArray Warrior Panel.
Time Frame: Two years through sample collection and analysis completion from 05/2020 to 05/2022.

Standard WHO-approved diagnostic testing uses bubo aspirates or sputum as clinical matrices to perform the following tests: F1RDT, qPCR analysis, and culture.

WHO defines a confirmatory positive plague case when the venous blood, bubo or sputum is positive on F1RDT and positive on either qPCR or culture.

Two years through sample collection and analysis completion from 05/2020 to 05/2022.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dawn J Birdsell, Ph.D., Northern Arizona University
  • Study Director: David M Wagner, Ph.D., Northern Arizona University
  • Study Director: Minoarisoa Rajerison, Ph.D., Institut Pasteur de Madagascar
  • Principal Investigator: Voahangy Andrianaivoarimanana, Ph.D., Institut Pasteur de Madagascar
  • Study Director: Chris Myers, Ph.D., Naval Health Research Center
  • Principal Investigator: Caroline Balagout, Naval Health Research Center
  • Study Chair: David P Trudil, New Horizons Diagnostics, Inc./Brimrose Biotechnology, Corp.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2020

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

January 1, 2023

Study Registration Dates

First Submitted

November 24, 2020

First Submitted That Met QC Criteria

December 28, 2020

First Posted (Actual)

December 30, 2020

Study Record Updates

Last Update Posted (Actual)

December 14, 2022

Last Update Submitted That Met QC Criteria

December 12, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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