Pharmacogenetics to avoid loss of hearing
| ISRCTN | ISRCTN13704894 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13704894 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 253102 |
| Protocol serial number | B00321, IRAS 253102 |
| Sponsor | Manchester University NHS Foundation Trust |
| Funder | National Institute for Health Research |
- Submission date
- 18/04/2019
- Registration date
- 25/04/2019
- Last edited
- 06/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Neonatal Diseases
Plain English summary of protocol
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
Contact information
Public
Manchester Centre for Genomic Medicine
6th Floor, St Mary’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
| Phone | +44 (0)1617019139 |
|---|---|
| rachel.mahood@mft.nhs.uk |
Scientific
Manchester Centre for Genomic Medicine
6th Floor, St Mary’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
| Phone | +44 (0)1617019139 |
|---|---|
| william.newman@manchester.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Multi-centre clinical feasibility study |
| Secondary study design | Feasibility study |
| Study type | Participant information sheet |
| Scientific title | Pharmacogenetics to avoid loss of hearing (clinical implementation study) |
| Study acronym | PALOH |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure(s) |
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 |
| Key secondary outcome measure(s) |
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 |
| Completion date | 30/11/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | All |
| Target sample size at registration | 900 |
| Total final enrolment | 751 |
| Key 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 |
| Key exclusion criteria | Neonates requiring antibiotics immediately with already established IV access |
| Date of first enrolment | 01/01/2020 |
| Date of final enrolment | 30/11/2020 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
Manchester
M13 9WL
United Kingdom
Crown Street
Liverpool
L8 7SS
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request, Published as a supplement to the results publication |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. William Newman (William.newman@manchester.ac.uk). Data pertaining to clinical timings associated with testing (e.g. time of NICU admission, time of swab, time of antibiotic administration etc) can be provided to researchers upon request to CI Prof Newman. Data will be anonymised. Consent for this data collection was presumed under an “opt-out” consent model. The datasets generated and/or analysed during the current study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Qualitative study | 07/01/2024 | 08/01/2024 | Yes | No |
| Results article | 21/03/2022 | 06/05/2025 | Yes | No | |
| Protocol article | 16/06/2021 | 18/06/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | 23/07/2020 | 06/05/2025 | Yes | No | |
| Other publications | 22/01/2021 | 06/05/2025 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
06/05/2025: Publication references and total final enrolment added.
08/01/2024: Publication reference added.
08/06/2022: Publication reference added.
02/11/2021: The intention to publish date was changed from 01/05/2021 to 31/12/2021. Individual participant data (IPD) sharing statement added.
18/06/2021: Publication reference added.
02/06/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/05/2020 to 30/11/2020.
2. A study contact was added.
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.
