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

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

Detailed Description
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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.

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

Conditions
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Ototoxic Hearing Loss, Ototoxic Hearing Loss, Bilateral, Ototoxicity, Tinnitus

Intervention / Treatment
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* Drug: N-acetyl cysteine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>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<br>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<br>* Injection of a 10% solution of N-acetylcysteine through transtympanic injection in both ears<br>* Other names: Lysomucil 10%;|

What is the study measuring?
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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 |