Evaluation of the Effect of Acetazolamide, Mannitol and N-acetylcysteine on Cisplatin-Induced Nephrotoxicity
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Mannitol group patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration. |
Drug: Mannitol
patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration.
Drug: saline
saline hydration 2500 ml before cisplatin therapy
Drug: Cisplatin
patients with tumours already prescribed cisplatin
|
| Active Comparator: ACTZ group patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration. |
Drug: Acetazolamide
patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration.for prevention of cisplatin nephrotoxicity
Other Names:
Drug: saline
saline hydration 2500 ml before cisplatin therapy
Drug: Cisplatin
patients with tumours already prescribed cisplatin
|
| Active Comparator: NAC group patients received acetylcysteine NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration. |
Drug: Acetylcysteine
patients received NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration.for prevention of cisplatin nephrotoxicity
Other Names:
Drug: saline
saline hydration 2500 ml before cisplatin therapy
Drug: Cisplatin
patients with tumours already prescribed cisplatin
|
Outcome Measures
Primary Outcome Measures
- Serum Creatinine [change from baseline after 3 cycles separated by 21 days]
Blood samples collected and measured in laboratory with the unit mg/dL
- Creatinine clearance according to Cockroft-Gault equation [change from baseline after 3 cycles separated by 21 days]
calculated using globalrph calculators , unit ml/min
- Acute kidney injury [change from baseline after 3 cycles separated by 21 days]
Acute kidney injury assessed by RIFLE criteria that was calculated for patients
- Blood urea nitrogen (BUN) [change from baseline after 3 cycles separated by 21 days]
Blood samples collected and measured in laboratory with the unit mg/dl
Secondary Outcome Measures
- Aspartate Transaminase (AST) [change from baseline after 3 cycles separated by 21 days]
Liver function tests were monitored by measuring AST for change from baseline after 3 cycles separated by 21 days
- hemoglo bin [change from baseline after 3 cycles separated by 21 days]
hemoglobin concentration g/dl was monitored for change from baseline after 3 cycles separated by 21 days
- adverse events [change from baseline after 3 cycles separated by 21 days]
Monitoring adverse events: to evaluate the difference between three groups regarding frequency of adverse events.
- Alanine Transaminase (ALT) [change from baseline after 3 cycles separated by 21 days]
Liver function tests were monitored by measuring ALT for change from baseline after 3 cycles separated by 21 days
- platelets count [change from baseline after 3 cycles separated by 21 days]
platelets count cells per ml was monitored for change from baseline after 3 cycles separated by 21 days
- total leucocyte count [change from baseline after 3 cycles separated by 21 days]
total leucocyte count cells per ml was monitored for change from baseline after 3 cycles separated by 21 days
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Cancer patients to receive cisplatin based chemotherapy protocol.
-
Adult patients from 18 to 65 years.
Exclusion Criteria:
-
Existing renal impairment ( Creatinine clearance <30 ml/minute)
-
Severe hepatic impairment (Child Pugh score C).
-
Hypersensitivity to sulfonamides.
-
Patients with chronic non-congestive angle closure glaucoma.
-
Hypersensitivity to sulphur compounds, N-acetylcysteine or any component of the formulation.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Ain Shams University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- master