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
Dr Rachel Mahood
Manchester Centre for Genomic Medicine
St Mary’s Hospital
B00321, IRAS 253102
Pharmacogenetics to avoid loss of hearing (clinical implementation study)
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.
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;
email@example.com), ref: 19/NW/0400
Previous ethics approval:
NHS Health Research Authority Research Ethics Service - approval pending
Multi-centre clinical feasibility study
Primary study design
Secondary study design
Patient information sheet
Not available in a web format, please use contact details to request a participant information sheet.
Neonatal intensive care
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.
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
Overall trial end date
Reason abandoned (if study stopped)
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
Target number of participants
Participant exclusion criteria
Neonates requiring antibiotics immediately with already established IV access
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Manchester University NHS Foundation Trust
Trial participating centre
Liverpool Women's NHS Foundation Trust
Liverpool Women’s Hospital Crown Street
National Institute for Health Research
Funding Body Type
Funding Body Subtype
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
Participant level data
To be made available at a later date
Basic results (scientific)