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

Cisplatin Nephrotoxicity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02760901
• Other study ID #: master
• Status: Completed
• Phase: Phase 2
• First received: April 1, 2016
• Last updated: January 23, 2017
• Start date: November 2013
• Est. completion date: October 2016

Study information

• Verified date: January 2017
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: October 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cisplatin Nephrotoxicity

Intervention

Drug:
• Acetazolamide
patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration.for prevention of cisplatin nephrotoxicity
• 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
• Mannitol
patients received mannitol 20 % 100 ml half an hour before cisplatin and saline hydration.
• saline
saline hydration 2500 ml before cisplatin therapy
• Cisplatin
patients with tumours already prescribed cisplatin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Creatinine	Blood samples collected and measured in laboratory with the unit mg/dL	change from baseline after 3 cycles separated by 21 days
Primary	Creatinine clearance according to Cockroft-Gault equation	calculated using globalrph calculators , unit ml/min	change from baseline after 3 cycles separated by 21 days
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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