The Pharmacogenetics to Avoid Loss of Hearing (PALOH) Trial: A Protocol for a Prospective Observational Implementation Trial

William Newman; John Mcdermott; Rachel Mahood; Ajit Mahaveer; Iain Bruce; Rick Body; Fiona Ulph; Nicola Booth; Rhona Macleod; Paul Wilson

doi:10.1136/bmjopen-2020-044457

The Pharmacogenetics to Avoid Loss of Hearing (PALOH) Trial: A Protocol for a Prospective Observational Implementation Trial

William Newman, John Mcdermott, Rachel Mahood, Ajit Mahaveer, Iain Bruce, Rick Body, Fiona Ulph, Nicola Booth, Rhona Macleod, Paul Wilson

Manchester University NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

Abstract

INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.

METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.

ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.

TRIAL REGISTRATION NUMBER: ISRCTN13704894.

PROTOCOL VERSION: V 1.3.

Original language	English
Article number	e044457
Journal	BMJ Open
Volume	11
Issue number	6
DOIs	https://doi.org/10.1136/bmjopen-2020-044457
Publication status	Published - 16 Jun 2021

Keywords

Deafness
Hearing
Humans
Infant, Newborn
Observational Studies as Topic
Pharmacogenetics
Point-of-Care Testing
Prospective Studies

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10.1136/bmjopen-2020-044457Licence: CC BY

(MCHP) : Manchester Centre for Health Psychology
Peters, S. (PI), Ulph, F. (PI), Arden Armitage, C. (Researcher), Borrelli, B. (Researcher), Bowen, A. (Researcher), Byrne-Davis, L. (Researcher), Edge, D. (Researcher), French, D. (Researcher), Hart, J. (Researcher), Todd, C. (Researcher), Skevington, S. (Researcher), Wearden, A. (Researcher), Cotterill, S. (Researcher), Brooks, J. (Researcher), Brown, L. (Researcher), Bull, E. (Researcher), Cordingley, L. (Researcher), Epton, T. (Researcher), Smith, D. (Researcher), Speer, S. (Researcher), Powell, R. (Researcher), Bartlett, K. (Researcher), Coupe, N. (Researcher), Shepherd, S. (Researcher), Dienes, K. (Researcher), Ghio, D. (Researcher), Hood, A. (Researcher), Lavallee, J. (Researcher), Rowland, C. (Researcher), Benton, J. (Researcher), Goldthorpe, J. (Researcher), McWilliams, L. (Researcher), Keyworth, C. (Researcher), Goulding, R. (Researcher), Loughran, M. (Researcher), Hawkes, R. (Researcher), Kapadi, A. (Researcher), Hurley, R. (Researcher), Leather, J. (Researcher), Musa, C. (Researcher), Angelakis, I. (Researcher), Reid, C. (Researcher), Reid, H. (PGR student), Hulme, L. (PGR student), Hindmarch, S. (PGR student), Plant, S. (Researcher), Peterson, J. (Researcher), Woof, V. (PGR student), Devereux-Fitzgerald, A. (Researcher), Sawyer, C. (Researcher), Wilkes, J. (Researcher), Birtwell, K. (Researcher), Stringer, G. (Researcher), Tang, M. Y. (Researcher), Coupe, N. (Researcher), Hamnett, C. (Support team), Lyons, S. (Researcher), Hulme, L. (PGR student) & Lee, R. (Researcher)
1/09/10 → …
Project: Research

World-first bedside genetic test to prevent babies going deaf
Newman, W. (Corresponding participant), Mcdermott, J. (Participant), Body, R. (Participant), Ulph, F. (Participant), Wilson, P. (Participant), Bruce, I. (Participant) & Beaman, G. (Participant)
Impact: Health and wellbeing, Economic, Technological, Policy

Cite this

@article{cd26760e01b44d86809629db265656de,

title = "The Pharmacogenetics to Avoid Loss of Hearing (PALOH) Trial: A Protocol for a Prospective Observational Implementation Trial",

abstract = "INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.TRIAL REGISTRATION NUMBER: ISRCTN13704894.PROTOCOL VERSION: V 1.3.",

keywords = "Deafness, Hearing, Humans, Infant, Newborn, Observational Studies as Topic, Pharmacogenetics, Point-of-Care Testing, Prospective Studies",

author = "William Newman and John Mcdermott and Rachel Mahood and Ajit Mahaveer and Iain Bruce and Rick Body and Fiona Ulph and Nicola Booth and Rhona Macleod and Paul Wilson",

note = "Funding Information: Funding Funding for the project was provided via an NIHR i4i programme award (Grant Number: II-LB-0417-20002), with additional support from the Manchester NIHR Biomedical Research Centre, Hearing Health Theme (IS-BRC-1215-20007). Pilot data support from Action on Hearing Loss Flexi grant F67_Newm. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.",

year = "2021",

month = jun,

day = "16",

doi = "10.1136/bmjopen-2020-044457",

language = "English",

volume = "11",

journal = "BMJ Open",

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TY - JOUR

T1 - The Pharmacogenetics to Avoid Loss of Hearing (PALOH) Trial: A Protocol for a Prospective Observational Implementation Trial

AU - Newman, William

AU - Mcdermott, John

AU - Mahood, Rachel

AU - Mahaveer, Ajit

AU - Bruce, Iain

AU - Body, Rick

AU - Ulph, Fiona

AU - Booth, Nicola

AU - Macleod, Rhona

AU - Wilson, Paul

N1 - Funding Information: Funding Funding for the project was provided via an NIHR i4i programme award (Grant Number: II-LB-0417-20002), with additional support from the Manchester NIHR Biomedical Research Centre, Hearing Health Theme (IS-BRC-1215-20007). Pilot data support from Action on Hearing Loss Flexi grant F67_Newm. Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

PY - 2021/6/16

Y1 - 2021/6/16

N2 - INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.TRIAL REGISTRATION NUMBER: ISRCTN13704894.PROTOCOL VERSION: V 1.3.

AB - INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.TRIAL REGISTRATION NUMBER: ISRCTN13704894.PROTOCOL VERSION: V 1.3.

KW - Deafness

KW - Hearing

KW - Humans

KW - Infant, Newborn

KW - Observational Studies as Topic

KW - Pharmacogenetics

KW - Point-of-Care Testing

KW - Prospective Studies

U2 - 10.1136/bmjopen-2020-044457

DO - 10.1136/bmjopen-2020-044457

M3 - Article

C2 - 34135034

SN - 2044-6055

VL - 11

JO - BMJ Open

JF - BMJ Open

IS - 6

M1 - e044457

ER -

The Pharmacogenetics to Avoid Loss of Hearing (PALOH) Trial: A Protocol for a Prospective Observational Implementation Trial

Abstract

Keywords

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Projects

(MCHP) : Manchester Centre for Health Psychology

Impacts

World-first bedside genetic test to prevent babies going deaf

Cite this