Evaluation of the Effect of Acetazolamide, Mannitol and N-acetylcysteine on Cisplatin-Induced Nephrotoxicity
- Conditions
- Cisplatin Nephrotoxicity
- Interventions
- Registration Number
- NCT02760901
- Lead Sponsor
- Ain Shams University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- Cancer patients to receive cisplatin based chemotherapy protocol.
- Adult patients from 18 to 65 years.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mannitol group saline patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration. ACTZ group Acetazolamide patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration. ACTZ group saline patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration. NAC group saline patients received acetylcysteine NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration. Mannitol group Cisplatin patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration. Mannitol group Mannitol patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration. NAC group Acetylcysteine patients received acetylcysteine NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration. ACTZ group Cisplatin patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration. NAC group Cisplatin patients received acetylcysteine NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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