Evaluation of the Effect of Acetazolamide, Mannitol and N-acetylcysteine on Cisplatin-Induced Nephrotoxicity

Ain Shams University

Status and phase: Completed; Phase 2

Conditions: Cisplatin Nephrotoxicity

Treatments: Drug: saline; Drug: Cisplatin; Drug: Acetazolamide; Drug: Mannitol; Drug: Acetylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT02760901

master

Details and patient eligibility

About

Cisplatin is a major anti-neoplastic drug used for the treatment of solid tumors. Its chief dose limiting side effect is nephrotoxicity. Twenty percent of patients receiving high-dose cisplatin undergo severe renal dysfunction. Acetazolamide and N-acetylcysteine (NAC) ameliorated Cisplatin-induced nephrotoxicity in rats. No study to date evaluated the protective effect of acetazolamide or NAC against cisplatin nephrotoxicity in humans.

Aim of the study was to evaluate the effect of acetazolamide or NAC against cisplatin nephrotoxicity in humans compared to mannitol and to each other.

Patients and methods. A total 52 patients receiving standard hydration measures for cisplatin were randomized to three groups: 20 patients receiving mannitol, 15 patients receiving acetazolamide and 17 patients receiving NAC. Patients' kidney function was monitored using serum creatinine, creatinine clearance and blood urea nitrogen; kidney injury was assessed using RIFLE criteria. Patients' liver function tests and hematological parameters were also monitored.

Enrollment: 52 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Cancer patients to receive cisplatin based chemotherapy protocol.
2. Adult patients from 18 to 65 years.

Exclusion criteria

1. Existing renal impairment ( Creatinine clearance <30 ml/minute)
2. Severe hepatic impairment (Child Pugh score C).
3. Hypersensitivity to sulfonamides.
4. Patients with chronic non-congestive angle closure glaucoma.
5. Hypersensitivity to sulphur compounds, N-acetylcysteine or any component of the formulation.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 3 patient groups

Mannitol group

Active Comparator group

Description:

patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration.

Treatment:

Drug: Mannitol

Drug: Cisplatin

Drug: saline

ACTZ group

Active Comparator group

Description:

patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration.

Treatment:

Drug: Acetazolamide

Drug: Cisplatin

Drug: saline

NAC group

Active Comparator group

Description:

patients received acetylcysteine NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration.

Treatment:

Drug: Acetylcysteine

Drug: Cisplatin

Drug: saline