Yersinia Pestis Lateral Flow Immunoassay for Blood Samples

Plague Clinical Trial

— SMARTPRT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04688996
• Other study ID #: Plague Lateral Flow Assay
• Secondary ID: Evaluation of di
• Status: Recruiting
• Start date: October 19, 2020
• Est. completion date: January 2023

Study information

• Verified date: August 2022
• Source: Brimrose Technology Corporation
• Contact: David P Trudil
• Phone: 410-499-7062
• Email: Davidt[@]nhdetect.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT04562012

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bubo; Yersinia Pestis
• Bubonic; Plague, Skin
• Plague
• Plague, Bubonic
• Plague, Pneumonic
• Pneumonic Plague
• Yersinia Pestis Infection
• Yersinia Pestis Plague
• Yersinia Pestis; Bubo
• Yersinia Pestis; Pneumonia
• Yersinia Sepsis

Intervention

Diagnostic Test:
• Lateral Flow Assay for Pathogens of the Plague
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).

Locations

Country	Name	City	State
Madagascar	Institut Pasteur de Madagascar	Antananarivo	Analamanga
United States	US Naval Health Research Center	San Diego	California

Sponsors (5)

Lead Sponsor	Collaborator
Brimrose Technology Corporation	Institut Pasteur de Madagascar, Naval Health Research Center, New Horizons Diagnostics Corporation, Northern Arizona University

Countries where clinical trial is conducted

United States,  Madagascar, 

References & Publications (6)

Andrianaivoarimanana V, Kreppel K, Elissa N, Duplantier JM, Carniel E, Rajerison M, Jambou R. Understanding the persistence of plague foci in Madagascar. PLoS Negl Trop Dis. 2013 Nov 7;7(11):e2382. doi: 10.1371/journal.pntd.0002382. eCollection 2013 Nov. — View Citation

Chanteau S, Rahalison L, Ralafiarisoa L, Foulon J, Ratsitorahina M, Ratsifasoamanana L, Carniel E, Nato F. Development and testing of a rapid diagnostic test for bubonic and pneumonic plague. Lancet. 2003 Jan 18;361(9353):211-6. doi: 10.1016/S0140-6736(03)12270-2. — View Citation

Inglesby TV, Dennis DT, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Koerner JF, Layton M, McDade J, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Schoch-Spana M, Tonat K. Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 2000 May 3;283(17):2281-90. doi: 10.1001/jama.283.17.2281. — View Citation

International meeting on preventing and controlling plague: the old calamity still has a future. Wkly Epidemiol Rec. 2006 Jul 14;81(28):278-84. No abstract available. English, French. — View Citation

Rasoamanana B, Leroy F, Boisier P, Rasolomaharo M, Buchy P, Carniel E, Chanteau S. Field evaluation of an immunoglobulin G anti-F1 enzyme-linked immunosorbent assay for serodiagnosis of human plague in Madagascar. Clin Diagn Lab Immunol. 1997 Sep;4(5):587-91. doi: 10.1128/cdli.4.5.587-591.1997. — View Citation

Stenseth NC, Atshabar BB, Begon M, Belmain SR, Bertherat E, Carniel E, Gage KL, Leirs H, Rahalison L. Plague: past, present, and future. PLoS Med. 2008 Jan 15;5(1):e3. doi: 10.1371/journal.pmed.0050003. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	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.
Primary	LFI results on finger-prick blood correlate with the results of standard WHO-approved diagnostic tests for plague	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	LFI results on finger-prick blood correlate with LFI results from bubo aspirate or sputum clinical matrices.	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.

External Links

•   Institut Pasteur de Madagascar
•   Northern Arizona Univerity Pathogen and Microbiome Institute