Drug Nephrotoxicity Amelioration by N-acetylcysteine

NCT ID: NCT06122311

Last Updated: 2024-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-25
• Study Completion Date: 2024-06-10

Brief 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.

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 .

Conditions

Drug-Induced Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

N-acetylcysteine

amphotericin b (0.5-1.25 mg/kg )over 6-8 hours +NAC 600mg twice daily throughout amphotericin b treatment

Group Type: EXPERIMENTAL

N Acetylcysteine

Intervention Type: DRUG

N-acetylcysteine sachets 600 mg twice daily

amphotericin b

amphotericin b (0.5-1.25mg/kg)over 6-8 hours infusion

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

N Acetylcysteine

N-acetylcysteine sachets 600 mg twice daily

Intervention Type: DRUG

Other Intervention Names

Acetylcysteine

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helwan University

OTHER

Sponsor Role: lead

Responsible Party

Yasmin medhat munir Mohamed

Teaching assistant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

yasmin munir, master

Role: PRINCIPAL_INVESTIGATOR

Helwan University

Locations

Helwan University

Cairo, , Egypt

Countries

Egypt

References

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.

Reference Type: BACKGROUND

PMID: 26050706 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19414577 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15637469 (View on PubMed)

Ebid AIM, Mohamed HS, Mohammed YMM, Mohamed Abdel Motaleb SM. Efficacy, Safety, and Cost-Effectiveness of N-Acetylcysteine in Preventing Amphotericin B Nephrotoxicity in Egyptian Patients with Hematological Malignancies: A Randomized Controlled Trial. Hosp Pharm. 2025 May 6:00185787251337615. doi: 10.1177/00185787251337615. Online ahead of print.

Reference Type: DERIVED

PMID: 40342610 (View on PubMed)

Other Identifiers

ANP

Identifier Type: -

Identifier Source: org_study_id