Drug Nephrotoxicity Amelioration by N-acetylcysteine

Study Overview
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Brief Summary
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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
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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 .

Official Title
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Drug Nephrotoxicity Amelioration in Cancer Patients by N-acetylcysteine

Conditions
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Drug-Induced Nephropathy

Intervention / Treatment
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* Drug: N Acetylcysteine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention and control groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine<br>amphotericin b (0.5-1.25 mg/kg )over 2-4 hours +NAC 600mg twice daily throughout amphotericin b treatment | Drug: N Acetylcysteine<br>* N-acetylcysteine sachets 600 mg twice daily<br>* Other names: Acetylcysteine;|
| No Intervention: amphotericin b<br>amphotericin b (0.5-1.25mg/kg)over 2-4 hours infusion | |

What is the study measuring?
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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 |