Drug Nephrotoxicity Amelioration by N-acetylcysteine

Drug Nephrotoxicity Amelioration in Hematological Malignancies Patients by N-acetylcysteine

When treating individuals with febrile neutropenia, amphotericin B (AmB-d) is one of the most effective treatments against often fatal systemic fungal infections.Nephrotoxicity from amphotericin B can develop with an incidence of up to 80.This emphasizes the value of nephroprotectant agent use.Because of N-acetylcysteine's antioxidant, antiapoptotic, vasodilator properties and its therapeutic effects on contrast nephropathy. Acetylcysteine's impact on amphotericin B-induced nephrotoxicity in cancer patients is assessed.

Study Overview

• Status: Completed
• Conditions: Drug-Induced Nephropathy
• Intervention / Treatment: Drug: N Acetylcysteine

Detailed Description

Severe fungal infections continue to be a significant source of morbidity and mortality in haematology units despite recent therapeutic advancements. The first anti-fungal medication that was successful against systemic mycoses was characterised as the traditional amphotericin B in the middle of the 1950s.AMB remains the treatment of choice for many serious fungal infections in vulnerable hosts owing to its excellent spectrum of activity and its low resistance rates. To date, it continues to be the agent with the widest spectrum of action and the lowest resistance potential of any known antifungal agent.In spite of clinical effectiveness, AmB treatment is associated with a range of acute and chronic adverse reactions . Nephrotoxicity and consequent electrolytes imbalances have been demonstrated as the most clinically significant adverse reaction of AmB that can restrict its clinical utility. Up to 80 % of AmB recipients during the first two weeks of treatment may develop some degree of reversible kidney injury . In addition, nearly 15 % of these patients may require dialysis which can lead to prolongation of hospital stay, increased total treatment costs, and mortality .

N-acetylcysteine, a drug with vasodilating, antiapoptotic, and anti-oxidant features, has been found to diminish the nephrotoxicity of cisplatin , cyclosporine and gentamicin . The results of two experimental studies in rats have suggested that N-acetylcysteine can mitigate GFR reduction as well as renal tubular apoptosis caused by AmB .

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Helwan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age more than 18 years.
• Patients who have indication for systemic (injection) for conventional amphotericin at least 7 days.

Exclusion Criteria:

• documented acute kidney injury defined by an increase in serum creatinine ‡ 0.3 mg/dl within 48 h, or an increase in serum creatinine by ‡ 1.5 times baseline within the prior 7 days, or urine volume <0.5 ml/kg/h for 6 h
• documented chronic kidney disease (clearance creatinine below 60 ml/min/1.73 m2 calculated by the abbreviated Modification of Diet in Renal Disease equation), history of peritoneal or hemodialysis for > 3 months
• sepsis
• Severe hemorrhage(Blood loss > 3 litres)
• Patient with cardiac or chronic liver disease history of receiving AmB by any administration route within the recent 14 days known allergy to either amphotericin b or N-acetylcysteine.
• receiving any formulation of NAC within the last week.
• unable to tolerate oral intake.

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
Experimental: N-acetylcysteine; amphotericin b (0.5-1.25 mg/kg )over 6-8 hours +NAC 600mg twice daily throughout amphotericin b treatment	Drug: N Acetylcysteine; N-acetylcysteine sachets 600 mg twice daily; Other Names: Acetylcysteine
No Intervention: amphotericin b; amphotericin b (0.5-1.25mg/kg)over 6-8 hours infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of nephrotoxicity	minimum of 0.3 mg/dL increase in serum creatinine within 48 hours from amphotericin B initiation.	During the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
electrolyte imbalances	Hypokalemia and hypomagnesemia were defined as serum potassium levels less than 3 mEq/L and serum magnesium levels less than 1.2 mEq /L, respectively.	During the intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cost effectiveness analysis	incremental cost effectiveness ratio	From start of amphotericin b to discharge or death ,whichever came first or up to 120 days
length of hospital stay(days)	duration a patient spends in a hospital	From start of amphotericin b to discharge or death ,whichever came first or up to 120 days

Collaborators and Investigators

• Sponsor: Helwan University
• Investigators: Principal Investigator: yasmin munir, master, Helwan University

Publications and helpful links

General Publications

• Karimzadeh I, Khalili H, Sagheb MM, Farsaei S. A double-blinded, placebo-controlled, multicenter clinical trial of N-acetylcysteine for preventing amphotericin B-induced nephrotoxicity. Expert Opin Drug Metab Toxicol. 2015;11(9):1345-55. doi: 10.1517/17425255.2015.1042363. Epub 2015 Jun 11.
• Odabasi Z, Karaalp A, Cermik H, Mohr J, Tigen ET, Koc M, Korten V. Reduction of amphotericin B-induced renal tubular apoptosis by N-acetylcysteine. Antimicrob Agents Chemother. 2009 Jul;53(7):3100-2. doi: 10.1128/AAC.00001-09. Epub 2009 May 4.
• Feldman L, Efrati S, Dishy V, Katchko L, Berman S, Averbukh M, Aladjem M, Averbukh Z, Weissgarten J. N-acetylcysteine ameliorates amphotericin-induced nephropathy in rats. Nephron Physiol. 2005;99(1):p23-7. doi: 10.1159/000081799.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Actual): June 10, 2024
• Study Completion (Actual): June 10, 2024

Study Registration Dates

• First Submitted: November 1, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 8, 2023

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; 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: ANP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No