Role of N-Acetylcysteine for Prevention of Cisplatin-induced Nephrotoxicity

Cisplatin is one of the first-line drugs used against many malignancies, such as lung cancer, head and neck cancer, esophageal cancer, gastric cancer, colorectal cancer, urothelial cancer, bladder cancer and testicular cancer. The usage of Cisplatin is limited by its severe nephrotoxicity, which particularly affects the proximal tubule epithelial cells (PTEC).Several studies suggest role of NAC in ameliorating Cisplatin induced nephrotoxicity, although definitive data is lacking. N-Acetylcysteine (NAC) is a thiol-containing antioxidant, which not only acts as a precursor of glutathione but also as a direct antioxidant .There are multiple postulated mechanisms for NAC's nephroprotection. NAC is a low-cost, easily available drug with a very good safety profile and therefore can be added as a support medication during treatment with cisplatin. The investigators plan to administer 1200 mg oral NAC 12 hours before chemotherapy and then daily at night for the subsequent 6 days, with an objective to ascertain its nephroprotective role in population receiving Cisplatin/-based chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Drug Toxicity
• Intervention / Treatment: Drug: Chemotherapy; Drug: N-Acetylcysteine

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Punjab
    • Rawalpindi, Punjab, Pakistan, 46000
      • Medical Oncology department, Fauji Foundation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult female outpatients with non-hematological malignancies (Breast, ovary and head and neck squamous cell carcinomas)
• Having Eastern Cooperative Oncology Group(ECOG) Performance Status ≤2 who had never received platinum based Chemotherapy in past and were now scheduled to receive high-dose cisplatin chemotherapy.
• Patients were required to have estimated glomerular filtration rate (GFR)(according to Cockcroft-Gault formula) ≥ 60 ml/min at start of chemotherapy regimen with normal Blood Counts, Liver, and kidney function tests

Exclusion Criteria:

• Patients who had poor performance status i.e., ECOG Performance Status 3 or 4
• Who declined to participate at any time during the course of the study
• Patients having hepatic failure (Liver Function tests >3 times of upper limit normal)
• Patients who did not tolerate the use of NAC or were administered the drug <70% of the time
• Patient who were receiving concurrent nephrotoxic drugs, or having history of Hypersensitivity to N-Acetyl cysteine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cisplatin group; This group of Patients will receive Cisplatin-base chemotherapy as per the designated schedule, alongside standard hydration protocol	Drug: Chemotherapy; Cisplatin-base chemotherapy as per the designated schedule, alongside standard hydration protocol.
Experimental: N-acetylcysteine group; Patients in the NAC arm to be given N-acetylcysteine 1200 mg/day starting 12 hrs before till 6 days after Cisplatin-based chemotherapy administration. Hydration according to standard hydration protocol will be given.	Drug: Chemotherapy; Cisplatin-base chemotherapy as per the designated schedule, alongside standard hydration protocol.; Drug: N-Acetylcysteine; Patients in the NAC arm will receive1200 mg of NAC (water-soluble granule Preparation) administered orally once daily at night for 7 consecutive days (1 days before chemotherapy, on the day of chemotherapy, and 5 days after chemotherapy) in each cycle of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine of participant	Blood samples collected and measured in laboratory with the unit mg/dL	18 weeks
Creatinine clearance of participant	It will be calculated using Cockroft-Gault formula , unit ml/min	18 weeks
Estimation of Acute kidney injury to participant	Acute kidney injury will be assessed by RIFLE criteria that will be calculated for patients	18 weeks
Blood urea nitrogen of participant	Blood samples collected and measured in laboratory with the unit mg/dl	18 weeks

Collaborators and Investigators

• Sponsor: Foundation University Islamabad

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Estimated): February 9, 2024
• Study Completion (Estimated): March 9, 2024

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Estimated): August 31, 2023

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: FUI/CTR/2023/14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No