Protocol plans randomized comparison of kidney-protective drugs during HIPEC

A prospective, randomized, double-blind, non-inferiority trial will compare intravenous cilastatin with sodium thiosulfate for preventing acute kidney injury in adults undergoing cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy with cisplatin. The study protocol sets out planned methods and outcome measures rather than clinical results, so it does not yet show whether cilastatin is as protective as thiosulfate, safer than thiosulfate, or suitable as a substitute for the established nephroprotection regimen used in this setting.

The trial is planned for 90 adults treated at a high-volume tertiary referral center. Eligible participants will undergo cytoreductive surgery and cisplatin-based HIPEC, a combined treatment used for selected patients with peritoneal malignancies. After randomization, patients will receive either cilastatin or sodium thiosulfate in a 1:1 ratio according to standardized perioperative nephroprotection regimens. The hospital pharmacy will manage randomization and drug preparation to conceal treatment allocation and maintain blinding among participants, clinicians and outcome assessors. The protocol notes that sodium thiosulfate is widely used during cisplatin-based HIPEC and has demonstrated effectiveness in reducing postoperative renal toxicity. It also identifies cilastatin as a drug with a long-standing clinical safety record that has shown consistent nephroprotective effects in experimental models and emerging clinical studies, while noting that comparative randomized evidence between the two approaches is lacking.

The primary outcome will be the incidence of acute kidney injury within the first seven postoperative days, determined under Kidney Disease Improving Global Outcomes, or KDIGO, criteria. With 90 participants, the trial is calculated to provide 80% power to demonstrate non-inferiority at a one-sided significance level of 0.025, using a predefined non-inferiority margin of 20%. The analysis will compare the two assigned nephroprotection strategies as they are used within routine clinical practice. Secondary outcomes will include cisplatin pharmacokinetics, the concentration of cisplatin in tumor nodules after HIPEC, and perioperative adverse events. The investigators will also track the evolution of renal dysfunction through postoperative day 14 among patients who develop acute kidney injury. Exploratory analyses will assess urinary biomarkers of renal injury, with the aim of providing additional information about the biology of kidney injury and protection. These are planned assessments: the protocol does not report differences in drug exposure, toxicity, renal outcomes or biomarker responses.

Acute kidney injury is described in the protocol as a common and clinically significant complication of cytoreductive surgery with cisplatin-based HIPEC, making perioperative nephroprotection an integral part of this treatment protocol. The trial addresses that defined risk in a specific surgical oncology population rather than kidney protection in cancer patients generally. Its single-center design, planned sample of 90 and focus on adults undergoing both cytoreductive surgery and HIPEC limit the scope of any eventual result. The protocol is registered in the EU Clinical Trials Information System as 2024-518854-18-00, in EudraCT as 2022-001417-39 and on ClinicalTrials.gov as NCT07229040. Until enrollment, follow-up, blinded outcome assessment and analysis are complete, the document provides no evidence of clinical benefit or safety equivalence between the drugs, nor does it establish which nephroprotective regimen should be preferred during cisplatin-based HIPEC.

Subject of Research: A randomized non-inferiority trial protocol comparing cilastatin and sodium thiosulfate for preventing acute kidney injury during cisplatin-based HIPEC.

Article Title: Cilastatin versus sodium thiosulfate for prevention of cisplatin-induced acute kidney injury during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized non-inferiority trial protocol

Article References: Nieto-Elizalde, J., Zaballos, M., González-Nicolas, M. Á., Lozano Lominchar, P., Palencia-García, N., Fernández-Vázquez, M. L., Vázquez-Ogando, E., Canal, M. I., Lázaro, A., & González Bayón, L. (2026). Cilastatin versus sodium thiosulfate for prevention of cisplatin-induced acute kidney injury during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized non-inferiority trial protocol. BMC Cancer. https://doi.org/10.1186/s12885-026-16831-4

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DOI: 10.1186/s12885-026-16831-4

Keywords: cilastatin, sodium thiosulfate, cisplatin, acute kidney injury, HIPEC, cytoreductive surgery, nephroprotection, randomized trial, clinical trial protocol, peritoneal malignancies, versus, sodium