Drug Nephrotoxicity Amelioration by N-acetylcysteine

Drug-Induced Nephropathy Clinical Trial

Official title:

Drug Nephrotoxicity Amelioration in Hematological Malignancies Patients by N-acetylcysteine

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06122311
• Other study ID #: ANP
• Status: Recruiting
• Phase: N/A
• Start date: July 16, 2023
• Est. completion date: May 30, 2024

Study information

• Verified date: February 2024
• Source: Helwan University
• Contact: yasmin munir, master
• Phone: 00201093201956
• Email: Yasmin.Mohammed[@]pharm.helwan.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Drug-Induced Nephropathy
• Kidney Diseases

Intervention

Drug:
• N Acetylcysteine
N-acetylcysteine sachets 600 mg twice daily

Locations

Country	Name	City	State
Egypt	Helwan University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Helwan University

Country where clinical trial is conducted

Egypt, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of nephrotoxicity	minimum of 0.3 mg/dL increase in serum creatinine within 48 hours from amphotericin B initiation.	During the intervention
Secondary	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