Condition category
Neonatal Diseases
Date applied
18/04/2019
Date assigned
25/04/2019
Last edited
04/11/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Gentamicin is an antibiotic that is routinely used to treat or protect against infection in over 95% of babies admitted to Neonatal Intensive Care Units (NICUs). Some children have a genetic change (variant) that predisposes to severe hearing loss or total deafness after a single dose of gentamicin. About 1 in 500 people have this variant. Groups with a higher risk of repeated chest infections throughout their lives (i.e. people with cystic fibrosis) are routinely tested for this variant using a technique known as pyrosequencing. This current test takes at least three days to return a clinically relevant result. Newborn babies with suspected sepsis should be treated within the first hour of suspicion. The current genetic test is therefore unsuitable in this situation. The researchers have developed a point-of-care test (PoCT) to detect this genetic variant via a buccal (mouth) swab, delivering a reliable result in less than 40 minutes. This study aims to trial this new genetic testing approach in two large newborn intensive care units (NICUs). The aim is to assess the performance of this device in providing an accurate result, in a time that will indicate if the child can or cannot be treated with gentamicin (a safe alternative can be used), and therefore avoid the risk of deafness.

Who can participate?
Babies admitted to the NICU or requiring a screen for infection within 72 hours of birth

What does the study involve?
All participating babies are tested for the genetic variant before antibiotic treatment. There is no follow up as part of the study.

What are the possible benefits and risks of participating?
Babies included in this study will benefit from a rapid, non-invasive genetic test which will allow personalised antibiotic prescribing to avoid hearing loss in at-risk individuals. If successful, the use of this technology across the UK could avoid permanent, severe hearing loss in about 180 babies every year.

Where is the study run from?
1. Manchester University NHS Foundation Trust (UK)
2. Liverpool Women's NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
June 2018 to November 2020

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Rachel Mahood
rachel.mahood@mft.nhs.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Rachel Mahood

ORCID ID

Contact details

Manchester Centre for Genomic Medicine
6th Floor
St Mary’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
+44 (0)1617019139
rachel.mahood@mft.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

B00321, IRAS 253102

Study information

Scientific title

Pharmacogenetics to avoid loss of hearing (clinical implementation study)

Acronym

PALOH

Study hypothesis

A clinical implementation study to critically assess the use of a novel point-of-care pharmacogenetic testing device to detect neonates at risk of aminoglycoside-induced hearing loss secondary to the genetic variant m.1555A>G. The primary objective is to assess the performance of the device and any barriers to implementation.

Ethics approval

Current ethics approval as of 04/11/2019:
Approved 22/08/2019, North West - Liverpool East Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ;
nrescommittee.northwest-liverpooleast@nhs.net), ref: 19/NW/0400

Previous ethics approval:
NHS Health Research Authority Research Ethics Service - approval pending

Study design

Multi-centre clinical feasibility study

Primary study design

Observational

Secondary study design

Feasibility study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in a web format, please use contact details to request a participant information sheet.

Condition

Neonatal intensive care

Intervention

This study involves the use of a novel genetic test to detect the m.1555A>G variant which is associated with aminoglycoside-induced hearing loss. All neonates admitted to the participating neonatal intensive care units during the study period will be tested for this variant prior to antibiotic treatment, to allow personalised prescribing and avoiding permanent, irreversible hearing loss in at-risk individuals.

The intervention is a one-off genetic test at the point of admission to neonatal intensive care. The objective is to look at feasibility of incorporating the test into the current clinical pathway rather than the efficacy of the intervention, which is already known. There is no follow up period as part of the study.

Intervention type

Genetic

Phase

Drug names

Primary outcome measure

The total number of neonates who are successfully tested for the m. 1555A>G genetic variant out of all babies given antibiotics on admission or assessment in the two participating sites, measured using patient medical notes and real-time data collection at the end of the study period

Secondary outcome measures

1. The total number of neonates identified with the m. 1555A>G genetic variant, measured using retrospective data collection from device at the end of the study period
2. Average time from admission to antibiotic administration for all participants tested throughout the 6-month study period, measured using patient medical notes and real-time data collection
3. Total number of incidences where time to antibiotic administration exceeds the 60-minute target and the reasons for these, measured using patient medical notes and real-time data collection
4. Total number of assay failures within the 6-month testing period and the reasons for these, measured using retrospective data collection from device
5. Resource impact: additional staff time required to secure samples and undertake testing, measured using staff observations
6. Total number of babies where testing was not undertaken during the 6-month testing period and the reasons for these, measured using patient medical notes and real-time data collection
7. The overall correlation of the point-of-care testing result with the current in-house reference assay (pyrosequencing)

Overall trial start date

01/06/2018

Overall trial end date

30/11/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. All babies admitted to NICU at Manchester University NHS Foundation Trust (MFT, Oxford Road Campus) and Liverpool Women's NHS Foundation Trust (LWH), for 6 months commencing from the trial start date
2. Babies requiring a screen for infection within 72 hours of birth (an infection screen for suspected early onset neonatal infection) at LWH who are not formally admitted to the neonatal unit, for 6 months commencing from the trial start date

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

900

Participant exclusion criteria

Neonates requiring antibiotics immediately with already established IV access

Recruitment start date

01/01/2020

Recruitment end date

31/05/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Liverpool Women's NHS Foundation Trust
Liverpool Women’s Hospital Crown Street
Liverpool
L8 7SS
United Kingdom

Sponsor information

Organisation

Manchester University NHS Foundation Trust

Sponsor details

Oxford Road
Manchester
M13 9WL
United Kingdom
+44 (0)161 276 4125
lynne.webster@mft.nhs.uk

Sponsor type

Hospital/treatment centre

Website

https://mft.nhs.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The researchers intend to publish the protocol. Outcomes relating to the project will be published in peer-reviewed medical journals and presented at regional, national and international meetings for paediatrics, neonates, genetics and audiology. The researchers will work with Bliss (Charity for the care of neonates) and the National Deaf Children’s Society to disseminate the project outcomes through their websites and other media. Plans for an implementation strategy, if outcomes are positive, will be developed in consultation with NIHR.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/05/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

04/11/2019: The following changes have been made: 1. The ethics approval has been updated. 2. The IRAS number has been added. 3. The recruitment start date has been changed from 01/11/2019 to 01/01/2020. 23/04/2019: Trial's existence confirmed by the NIHR.