Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial

• Main Authors: Richard Body, Mark A Turner, William G Newman, John Henry McDermott, Gino Miele, Peter Roberts, Fiona Ulph, Rhona MacLeod, Shaun Ainsworth, Rachel Mahood, Duncan Stoddard, Ajit Mahaveer, Rachel Corry, Julia Garlick, Laura Kemp, Karen Harvey, Nicola Booth
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2021-06-01
• Series: BMJ Open
• Online Access: https://bmjopen.bmj.com/content/11/6/e044457.full

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.