Transtympanic sodium thiosulphate to prevent cisplatin-related hearing loss: a protocol for randomised controlled multicentre phase III trial, the SOUND trial.

Anouk V M Burger, Charlotte W Duinkerken, Jeroen C Jansen, Stijn Keereweer, Froukje L Cals, Robert J Stokroos, Jan Paul de Boer, Leonie Exterkate, Lilly-Ann van der Velden, Alexander E Hoetink, Bastiaan Nuijen, Michael Hauptmann, Klaske E van Sluis, Tjasse D Bruintjes, Charlotte L Zuur

Journal: BMJ open 2025;15(12):e107101

PMID: 41338634

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Abstract

INTRODUCTION

Cisplatin is a widely used chemotherapeutic anti-cancer drug. However, high-dose cisplatin is also known for its dose-limiting toxicities, including irreversible cisplatin-induced hearing loss (CIHL). Sodium thiosulphate (STS) can bind to cisplatin to form an inactive and harmless complex. A topical application is desired, allowing cisplatin to retain its systemic anti-cancer effect.

METHODS AND ANALYSIS

The SOUND trial is an investigator-initiated randomised controlled multicentre phase III trial to study the efficacy of transtympanic administration of STS against CIHL in a cohort of 100 patients with head and neck cancer treated with cisplatin at a dose of ≥200 mg/m². Each subject will receive transtympanic STS injections in one ear, chosen by randomisation, before each cisplatin infusion. The contralateral ear serves as an internal control. The primary objective is efficacy (ie, clinically relevant benefit) of transtympanic STS injections against CIHL, defined as a difference in threshold shift of ≥10 decibels between baseline and 3 months after treatment in favour of the STS-treated ear. Secondary objectives include the difference in mean threshold shifts on frequencies essential for speech and extended high frequencies, as well as the difference between both ears in the gradation of hearing loss as defined by ototoxicity grading scales.

ETHICS AND DISSEMINATION

The medical ethics committee in the Netherlands approved the trial (Clinical Trials Information System (CTIS) 2023-503313-30-00). The results will be disseminated through the CTIS and peer-reviewed scientific journals.

TRIAL REGISTRATION NUMBER

CTIS 2023-503313-30-00 approved by Medical Research Ethics Committee NedMec.

Address: Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.; Department of Otorhinolaryngology - Head and Neck surgery, Leiden University Medical Center, Leiden, Netherlands.; Department of Otorhinolaryngology - Head and Neck surgery, Leiden University Medical Center, Leiden, Netherlands.; Department of Otolaryngology, Medical Centre Haaglanden, The Hague, ZH, Netherlands.; Department of Otorhinolaryngology - Head and Neck surgery, Leiden University Medical Center, Leiden, Netherlands.; Department of Otolaryngology and Head and Neck Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, GE, Netherlands.; Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Centre Utrecht, Utrecht, Netherlands.; Department of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.; Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.; Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.; Biometrie und Registerforschung, Brandenburg Medical School Theodor Fontane, Neuruppin, Brandenburg, Germany.; Department of Otorhinolaryngology - Head and Neck surgery, Leiden University Medical Center, Leiden, Netherlands.; Gelre Hospitals, Apeldoorn, GE, Netherlands.; Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands [email protected].; Department of Otorhinolaryngology - Head and Neck surgery, Leiden University Medical Center, Leiden, Netherlands.

DOI: 10.1136/bmjopen-2025-107101

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MeSH Terms: Humans, Cisplatin, Hearing Loss, Antineoplastic Agents, Thiosulfates, Clinical Trials, Phase III as Topic, Head and Neck Neoplasms, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Adult, Female, Male, Injection, Intratympanic