Intratympanic Administration of N-acetylcysteine for Protection of Cisplatin-induced Ototoxicity

Clinical Trial: Intratympanic Injection of N-acetylcysteine for Protection of Cisplatin-induced Ototoxicity

The purpose of this study is to assess the efficacity of N-acetylcystein against Cisplatin-induced ototoxicity.

Study Overview

• Status: Terminated
• Conditions: Ototoxicity; Tinnitus; Ototoxic Hearing Loss; Ototoxic Hearing Loss, Bilateral
• Intervention / Treatment: Drug: N-acetyl cysteine

Detailed Description

This is a monocentric, randomized, controlled, open label phase IV superiority trial.

After signing the informed consent form and upon the confirmation of the patient eligibility, patients will be randomized 1:1 to the experimental arm (NAC + Cisplatin) or the standard arm (Cisplatin).

The primary objective of this trial is to evaluate the protecting effect of Lysomucil® 10% against Cisplatin-induced ototoxicity. In this case, we will evaluate its effect through the transtympanic administration in both ears.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gaëtan CAVELIER, MD; Phone Number: 003225354267; Email: gaetan_cavelier@stpierre-bre.be
• Study Contact Backup: Name: Mihaela Horoi, MD; Phone Number: 003225354267; Email: mihaela_horoi@stpierre-bru.be

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18-year-old
• Patients suffering from a neoplastic disease for which treatment protocol includes Cisplatin.

Exclusion Criteria:

• Women of childbearing potential pregnant or with intention to become pregnant within the trial duration
• Women who are breastfeeding
• Pathological findings on otoscopy that do not allow safe intratympanic drug delivery.
• Conductive hearing loss > 20dBHL
• Meniere disease
• Medical history of sudden hearing loss
• Sensoryneural Hearing loss (SNHL) with mean ≥ 40dbHL Pure Tonal Audiometry (PTA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard arm (Arm A): Cisplatin from 70 to 100 mg/m2 intravenous (IV) once for 3 to 7 cycles +/- Radiotherapy (depending on the type and the severity of the neoplastic disease) Dosis and number of Cisplatin cycles are determined by the oncologist depending on type and severity of neoplastic disease.
Experimental: N-acetylcysteine; Experimental arm (Arm B): 0.4 to 1 ml of NAC 10% through intratympanic injection (ITI) from 40 to 60 minutes maximum prior to each Cisplatin cycle.; Cisplatin from 70 to 100 mg/m2 intravenous (IV) once for 3 to 7 cycles +/- Radiotherapy (depending on the type and the severity of the neoplastic disease) Dosis and number of Cisplatin cycles are determined by the oncologist depending on type and severity of neoplastic disease.	Drug: N-acetyl cysteine; Injection of a 10% solution of N-acetylcysteine through transtympanic injection in both ears; Other Names: Lysomucil 10%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apparition of ototoxicity	the apparition of ototoxicity as defined by the International Common Terminology Criteria for Adverse Events (CTCAE), version 5: A Threshold shift of 15 - 25 decibel (dB) averaged at 2 contiguous test frequencies in at least one ear; and/or the apparition of a tinnitus (not previously present).	6 month after last injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the apparition of ototoxicity defined by the inclusion of high frequency audiometry (Tune Grading System)	the apparition of ototoxicity as defined by the International Common Terminology Criteria for Adverse Events (CTCAE), version 5: A Threshold shift of 15 - 25 dB averaged at 2 contiguous test frequencies in at least one ear; and/or the apparition of a tinnitus (not previously present).	6 month after last injection
Hearing quality of life: Evaluation of the Impact of Hearing Loss in Adults ERSA	Evaluation of the Impact of Hearing Loss in Adults (ERSA) For each question, the score of 0 means maximal difficulties, the sore of 10 means ideal situation Formulation is uniform, with no inversions: 0 always corresponds to maximal difficulty and 10 to an ideal situation, so that the lower the score the greater the impact of hearing loss on quality of life. Maximum score is 200 for respondents in work and 150 for those not in work or in retirement.	6 month after last injection
Hearing quality of life: Tinnitus Handicap Index (THI)	Tinnitus Handicap Index (THI) score Range : 0 to 100. Higher scores mean a worse outcome.	6 month after last injection

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre
• Investigators: Principal Investigator: Gaëtan Cavelier, MD, Centre Hospitalier Universitaire Saint Pierre

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2021
• Primary Completion (Actual): May 3, 2023
• Study Completion (Actual): September 3, 2023

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Hearing Loss; Ototoxicity; Deafness; Tinnitus; Hearing Loss, Bilateral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: CHUB-NAC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No