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

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • John Mcdermott
  • Rachel Mahood
  • Ajit Mahaveer
  • Iain Bruce
  • Nicola Booth
  • Rhona Macleod

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: The genedriveTM POCT can detect the m.1555A>G variant in 26 minutes 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 to data collected prior to implementation, measuring the impact on routine practice. Ethics and Dissemination: An opt-out consenting process was approved by the Research Ethics Committee (REC) in August 2019. Results will be published in full on completion of the study. Discussion: The m.1555A>G variant is associated with aminoglycoside induced ototoxicity. This was established in 1993, yet technology has not been available to rapidly test for the variant. The genedriveTM assay can detect the variant in a practice-changing timeframe. However, it has not been established whether such a test could be practically implemented. To our knowledge, this trial represents the first example of a genetic POCT being employed in the neonatal setting to alter management acutely.

Bibliographical metadata

Original languageEnglish
Article numbere044457
JournalBMJ Open
Volume11
DOIs
Publication statusPublished - 16 Jun 2021