Efficacy, Safety, and Cost-Effectiveness of N-Acetylcysteine in Preventing Amphotericin B Nephrotoxicity in Egyptian Patients with Hematological Malignancies: A Randomized Controlled Trial

<b>Introduction:</b> Amphotericin B (AmB-d) is one of the most common agents for treating fatal systemic fungal infections in patients with hematologic malignancies. However, its severe adverse effects, especially nephrotoxicity, limited its use. This study evaluated the efficacy, safety, and cost-effectiveness of oral N-acetylcysteine (NAC) in preventing AmB-d nephrotoxicity and promoting renal recovery in Egyptian hematological malignancy patients. <b>Methods:</b> A prospective open-label randomized controlled trial was conducted. Patients were randomized to receive AmB-d plus 600 mg NAC twice daily (intervention group) or AmB-d alone (control group). The primary outcome was the incidence of acute kidney injury (AKI), with secondary outcomes including electrolyte imbalances (hypokalemia, hypomagnesemia) and renal recovery from AKI. A cost-effectiveness analysis was performed, supported by one-way and probabilistic sensitivity analyses (PSA). <b>Results:</b> NAC co-treatment significantly reduced AmB-d-induced AKI (odds ratio = 0.415, 95% CI: 0.174-0.992, <i>P</i> = .041). Renal recovery rates were higher in the NAC group (73.33% vs 53.85%), though not statistically significant (<i>P</i> = .322); the number needed to treat (NNT) was 6, indicating clinical relevance. No significant differences were observed in hypokalemia (<i>P</i> = .547) or hypomagnesemia (<i>P</i> = .768). NAC was cost-effective, with an effectiveness gain of 0.22 and cost savings of 2742.678 EGP per patient. Sensitivity analyses confirmed robustness, with NAC being dominant in 942 out of 1000 PSA scenarios. NAC was well-tolerated, with only mild gastrointestinal side effects reported. <b>Conclusion:</b> NAC co-administration with AmB-d effectively prevents nephrotoxicity, reduces costs, and may promote renal recovery in Egyptian hematological malignancy patients. The favorable NNT for renal recovery suggests clinical relevance, warranting further investigation in larger studies. <b>Trial registration:</b> ClinicalTrials.gov identifier, NCT06122311.