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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04864873




Registration number
NCT04864873
Ethics application status
Date submitted
21/04/2021
Date registered
29/04/2021
Date last updated
2/08/2021

Titles & IDs
Public title
Evaluation of a mNGS Workflow for Infection Diagnosis Using Oxford Nanopore Sequencing.
Scientific title
An External Evaluation of a Metagenomic Next Generation Sequencing Workflow for Infection Diagnosis Using Oxford Nanopore Sequencing.
Secondary ID [1] 0 0
MNGS001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - Metagenomic next generation sequencing using Oxford Nanopore
Diagnosis / Prognosis - Standard microbiological diagnostic pathway

Active Comparator: Standard diagnostic pathway - Part of each patient sample will be tested using current standard microbiological techniques.

Experimental: mNGS pathway - Part of each sample will be testing using mNGS methodology, which will be compared to the standard diagnostic pathway.


Diagnosis / Prognosis: Metagenomic next generation sequencing using Oxford Nanopore
See previous.

Diagnosis / Prognosis: Standard microbiological diagnostic pathway
See previous.
Intervention code [1] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sensitivity of mNGS compared to standard pathway
Timepoint [1] 0 0
Within 1 week of sampling.
Primary outcome [2] 0 0
Specificity of mNGS compared to standard pathway
Timepoint [2] 0 0
Within 1 week of sampling.
Primary outcome [3] 0 0
Level of agreement between mNGS and standard pathway
Timepoint [3] 0 0
Within 1 week of sampling.
Primary outcome [4] 0 0
Changes to patient management in response to mNGS result
Timepoint [4] 0 0
Within 1 month of sampling.

Eligibility
Key inclusion criteria
- All samples received by the WSCL microbiology laboratory for testing for the purposes
of diagnosing infection will be eligible.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Use of residual sample for mNGS testing may leave too little remaining sample and
compromise standard diagnostic testing.

- Patients who have requested that their residual samples be returned to them.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2022
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
Capital and Coast District Health board
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Wellington Southern Community Laboratories
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Institute of Environmental Science and Research
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a laboratory evaluation of a new testing methodology for microbiological diagnosis,
whereby participant samples received as part of routine care will be divided between the
standard diagnostic pathway and this new pathway: metagenomic next generation sequencing
(mNGS). Results obtained from the mNGS pathway will be compared against the standard
diagnostic pathway in terms of sensitivity, specificity, accuracy and clinical impact. The
samples will be identified at Wellington Southern Community Laboratories (WSCL), which
provides laboratory services for Capital and Coast District Health Board, and forwarded to
the Institute of Environmental Science and Research (ESR) to undergo mNGS testing.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04864873
Trial related presentations / publications
Ivy MI, Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, Hanssen AD, Abdel MP, Chia N, Yao JZ, Tande AJ, Mandrekar JN, Patel R. Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing. J Clin Microbiol. 2018 Aug 27;56(9):e00402-18. doi: 10.1128/JCM.00402-18. Print 2018 Sep.
Sanderson ND, Street TL, Foster D, Swann J, Atkins BL, Brent AJ, McNally MA, Oakley S, Taylor A, Peto TEA, Crook DW, Eyre DW. Real-time analysis of nanopore-based metagenomic sequencing from infected orthopaedic devices. BMC Genomics. 2018 Sep 27;19(1):714. doi: 10.1186/s12864-018-5094-y.
Gu W, Deng X, Lee M, Sucu YD, Arevalo S, Stryke D, Federman S, Gopez A, Reyes K, Zorn K, Sample H, Yu G, Ishpuniani G, Briggs B, Chow ED, Berger A, Wilson MR, Wang C, Hsu E, Miller S, DeRisi JL, Chiu CY. Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids. Nat Med. 2021 Jan;27(1):115-124. doi: 10.1038/s41591-020-1105-z. Epub 2020 Nov 9.
Street TL, Sanderson ND, Atkins BL, Brent AJ, Cole K, Foster D, McNally MA, Oakley S, Peto L, Taylor A, Peto TEA, Crook DW, Eyre DW. Molecular Diagnosis of Orthopedic-Device-Related Infection Directly from Sonication Fluid by Metagenomic Sequencing. J Clin Microbiol. 2017 Aug;55(8):2334-2347. doi: 10.1128/JCM.00462-17. Epub 2017 May 10.
Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, Yao JZ, Chia N, Hanssen AD, Abdel MP, Patel R. Identification of Prosthetic Joint Infection Pathogens Using a Shotgun Metagenomics Approach. Clin Infect Dis. 2018 Oct 15;67(9):1333-1338. doi: 10.1093/cid/ciy303.
Langelier C, Kalantar KL, Moazed F, Wilson MR, Crawford ED, Deiss T, Belzer A, Bolourchi S, Caldera S, Fung M, Jauregui A, Malcolm K, Lyden A, Khan L, Vessel K, Quan J, Zinter M, Chiu CY, Chow ED, Wilson J, Miller S, Matthay MA, Pollard KS, Christenson S, Calfee CS, DeRisi JL. Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12353-E12362. doi: 10.1073/pnas.1809700115. Epub 2018 Nov 27.
Sanderson ND, Swann J, Barker L, Kavanagh J, Hoosdally S, Crook D; GonFast Investigators Group; Street TL, Eyre DW. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic Nanopore sequencing. Genome Res. 2020 Sep;30(9):1354-1363. doi: 10.1101/gr.262865.120. Epub 2020 Sep 1.
Rodino KG, Toledano M, Norgan AP, Pritt BS, Binnicker MJ, Yao JD, Aksamit AJ, Patel R. Retrospective Review of Clinical Utility of Shotgun Metagenomic Sequencing Testing of Cerebrospinal Fluid from a U.S. Tertiary Care Medical Center. J Clin Microbiol. 2020 Nov 18;58(12):e01729-20. doi: 10.1128/JCM.01729-20. Print 2020 Nov 18.
Wu X, Lai T, Jiang J, Ma Y, Tao G, Liu F, Li N. An on-site bacterial detection strategy based on broad-spectrum antibacterial epsilon-polylysine functionalized magnetic nanoparticles combined with a portable fluorometer. Mikrochim Acta. 2019 Jul 10;186(8):526. doi: 10.1007/s00604-019-3632-1.
Hasan MR, Rawat A, Tang P, Jithesh PV, Thomas E, Tan R, Tilley P. Depletion of Human DNA in Spiked Clinical Specimens for Improvement of Sensitivity of Pathogen Detection by Next-Generation Sequencing. J Clin Microbiol. 2016 Apr;54(4):919-27. doi: 10.1128/JCM.03050-15. Epub 2016 Jan 13.
Charalampous T, Kay GL, Richardson H, Aydin A, Baldan R, Jeanes C, Rae D, Grundy S, Turner DJ, Wain J, Leggett RM, Livermore DM, O'Grady J. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol. 2019 Jul;37(7):783-792. doi: 10.1038/s41587-019-0156-5. Epub 2019 Jun 24.
Ji XC, Zhou LF, Li CY, Shi YJ, Wu ML, Zhang Y, Fei XF, Zhao G. Reduction of Human DNA Contamination in Clinical Cerebrospinal Fluid Specimens Improves the Sensitivity of Metagenomic Next-Generation Sequencing. J Mol Neurosci. 2020 May;70(5):659-666. doi: 10.1007/s12031-019-01472-z. Epub 2020 Jan 31.
Public notes

Contacts
Principal investigator
Name 0 0
Maxim G Bloomfield, MBChB
Address 0 0
Wellington Southern Community Laboratories, Capital and Coast District Health Board
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Maxim G Bloomfield, MBChB
Address 0 0
Country 0 0
Phone 0 0
+64272089584
Fax 0 0
Email 0 0
maxim.bloomfield@ccdhb.org.nz
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04864873