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

NCT02760901 | Completed Phase 2

• 1 other identifier: master
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cisplatin Nephrotoxicity

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Aspartate Transaminase (AST)

  change from baseline after 3 cycles separated by 21 days

• hemoglo bin

  change from baseline after 3 cycles separated by 21 days

• adverse events

  change from baseline after 3 cycles separated by 21 days

• Alanine Transaminase (ALT)

  change from baseline after 3 cycles separated by 21 days

• platelets count

  change from baseline after 3 cycles separated by 21 days

Study Arms (3)

Mannitol group

ACTIVE COMPARATOR

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

Drug: Mannitol; Drug: saline; Drug: Cisplatin

ACTZ group

ACTIVE COMPARATOR

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

Drug: Acetazolamide; Drug: saline; Drug: Cisplatin

NAC group

ACTIVE COMPARATOR

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

Drug: Acetylcysteine; Drug: saline; Drug: Cisplatin

Interventions

Acetazolamide DRUG

patients received acetazolamide 250 mg half an hour before cisplatin with saline hydration.for prevention of cisplatin nephrotoxicity

Also known as: ACTZ

ACTZ group

Acetylcysteine DRUG

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

Also known as: NAC

NAC group

Mannitol DRUG

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

Mannitol group

saline DRUG

saline hydration 2500 ml before cisplatin therapy

ACTZ group; Mannitol group; NAC group

Cisplatin DRUG

patients with tumours already prescribed cisplatin

ACTZ group; Mannitol group; NAC group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ain Shams University: lead

MeSH Terms

Interventions

Acetazolamide; Acetylcysteine; Mannitol; Sodium Chloride; Cisplatin

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cysteine; Amino Acids, Sulfur; Amino Acids; Amino Acids, Peptides, and Proteins; Sugar Alcohols; Alcohols; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical pharmacist

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: May 4, 2016
• Study Start: November 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2016
• Last Updated: January 24, 2017

Record last verified: 2017-01