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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cisplatin Nephrotoxicity

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Acetylcysteine
* Drug: Mannitol
* Drug: saline
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mannitol group<br>patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration. | Drug: Mannitol<br>* patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration.<br>Drug: saline<br>* saline hydration 2500 ml before cisplatin therapy<br>Drug: Cisplatin<br>* patients with tumours already prescribed cisplatin<br>|
| Active Comparator: ACTZ group<br>patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration. | Drug: Acetazolamide<br>* patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration.for prevention of cisplatin nephrotoxicity<br>* Other names: ACTZ;Drug: saline<br>* saline hydration 2500 ml before cisplatin therapy<br>Drug: Cisplatin<br>* patients with tumours already prescribed cisplatin<br>|
| Active Comparator: NAC group<br>patients received acetylcysteine NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration. | Drug: Acetylcysteine<br>* patients received NAC (600 mg every 12 hours) for 4 doses beginning 24 hours before cisplatin with saline hydration.for prevention of cisplatin nephrotoxicity<br>* Other names: NAC;Drug: saline<br>* saline hydration 2500 ml before cisplatin therapy<br>Drug: Cisplatin<br>* patients with tumours already prescribed cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Creatinine | Blood samples collected and measured in laboratory with the unit mg/dL | change from baseline after 3 cycles separated by 21 days | 
| Creatinine clearance according to Cockroft-Gault equation | calculated using globalrph calculators , unit ml/min | change from baseline after 3 cycles separated by 21 days | 
| Acute kidney injury | Acute kidney injury assessed by RIFLE criteria that was calculated for patients | change from baseline after 3 cycles separated by 21 days | 
| Blood urea nitrogen (BUN) | Blood samples collected and measured in laboratory with the unit mg/dl | change from baseline after 3 cycles separated by 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aspartate Transaminase (AST) | Liver function tests were monitored by measuring AST for change from baseline after 3 cycles separated by 21 days | change from baseline after 3 cycles separated by 21 days | 
| hemoglo bin | hemoglobin concentration g/dl was monitored for change from baseline after 3 cycles separated by 21 days | change from baseline after 3 cycles separated by 21 days | 
| adverse events | Monitoring adverse events: to evaluate the difference between three groups regarding frequency of adverse events. | change from baseline after 3 cycles separated by 21 days | 
| Alanine Transaminase (ALT) | Liver function tests were monitored by measuring ALT for change from baseline after 3 cycles separated by 21 days | change from baseline after 3 cycles separated by 21 days | 
| platelets count | platelets count cells per ml was monitored for change from baseline after 3 cycles separated by 21 days | change from baseline after 3 cycles separated by 21 days | 
| total leucocyte count | total leucocyte count cells per ml was monitored for change from baseline after 3 cycles separated by 21 days | change from baseline after 3 cycles separated by 21 days |