N-acetylcysteine to prevent cisplatin-related hearing loss

Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial

This study tests whether N-acetylcysteine (NAC) can prevent hearing loss in adults receiving high-dose cisplatin chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Siriraj Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Bangkok, Bangkoknoi)
• Trial ID: NCT07364747 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial comparing NAC versus placebo in patients scheduled for high-dose cisplatin chemotherapy. Hearing is measured with pure-tone audiometry including extended high-frequency testing and distortion product otoacoustic emissions (DPOAE) at baseline, before each cisplatin cycle, and at 1 and 4 months after treatment completion. The primary endpoint is the change in hearing thresholds and pure-tone averages at one month after treatment, with statistical comparisons between groups using appropriate comparative tests. The study aims to determine feasibility and signal of otoprotection from NAC in a clinical chemotherapy setting.

Who should consider this trial

Good fit: Adults aged 18–70 scheduled to receive high-dose cisplatin regimens (each dose >50 mg/m2 and cumulative dose >200 mg/m2) who will receive care at Siriraj Hospital.

Not a fit: Patients with prior cochlear-directed high-dose head and neck radiation, nasopharyngeal carcinoma, or who recently received NAC are excluded and are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If effective, NAC could reduce or prevent permanent cisplatin-related hearing loss and help preserve patients' hearing and quality of life.

How similar studies have performed: Preclinical studies and some small clinical trials of antioxidants including NAC have suggested protective effects against ototoxicity, but human results to date have been mixed and not conclusive.

Eligibility criteria

Inclusion Criteria:

* Patients aged between 18 and 70 years
* Patients scheduled to receive high-dose cisplatin-based chemotherapy regimens with a projected cumulative cisplatin dose of \> 200 mg/m2 and each dose \> 50 mg/m2
* Patients may receive concurrent chemotherapy with non-ototoxic agents
* Patients may receive concurrent radiation therapy to the skull base, provided the radiation dose does not exceed the toxic threshold for ototoxicity
* Patients receiving an appropriate antiemetic regimen consisting of Olanzapine or Neurokinin-1 (NK1) receptor antagonists
* Patients receiving medical treatment at Siriraj Hospital.

Exclusion Criteria:

* Patients diagnosed with Nasopharyngeal Carcinoma (CA nasopharynx).
* Patients with a history of head and neck radiation therapy where the radiation dose to the cochlea exceeded 9 Gy or the dose to the eustachian tube exceeded 50 Gy on both sides.
* Patients who have received N-acetylcysteine (NAC) within 2 weeks prior to the start of the study.
* Patients who have received other ototoxic drugs within 2 weeks prior to or during the study, including but not limited to:

Aminoglycoside antibiotics, Vancomycin, Loop diuretics (e.g., Furosemide), High-dose Aspirin, Antimalarial drugs (e.g., Quinine)

\- Patient with a known allergy or hypersensitivity to acetylcysteine.

Where this trial is running

Bangkok, Bangkoknoi

• Faculty of Medicine Siriraj Hospital, Mahidol University — Bangkok, Bangkoknoi, Thailand (Recruiting)

Study contacts

• Principal investigator: Kanthong Thongyai, Master — Siriraj Hospital
• Study coordinator: Naphassakorn Opasatian, Bachelor

Conditions Cisplatin-induced Ototoxicity; Sensorineural Hearing Loss; Ototoxicity; Ototoxicity, Drug-Induced