Effect of Sodium Thiosulfate on Nephrotoxicity of Cisplatin Intraperitoneal Heat-perfusion Chemotherapy

Sun Yat-sen University

Status and phase: Not yet enrolling; Phase 2

Conditions: Epithelial Ovarian Cancer; Acute Kidney Injury Due to Circulatory Failure

Treatments: Drug: Cisplatin; Other: Hydration; Drug: Sodium Sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT05877911

SYSKY-2022-549-02

Details and patient eligibility

About

Ovarian cancer is the most lethal malignancy of the female genital tract. Cytoreductive surgery combined with chemotherapy is the primary treatment for ovarian cancer, and radical tumor resection is an important means to improve the prognosis. However, even after complete tumor resection, 75% of patients with ovarian cancer still recur within 3 years after the initial treatment and eventually die from recurrence. In ovarian cancer, the lesions are located primarily in the peritoneal cavity. High-grade evidence demonstrates that the use of intraperitoneal hyperthermic chemotherapy (HIPEC) with cisplatin after cytoreductive surgery significantly improves the outcome in some patients with ovarian cancer. Currently, this is the only non-pharmacologic treatment that reduces both the risk of recurrence and death from ovarian cancer with a multi treatment. However, HIPEC with cisplatin can lead to acute kidney injury, and a serious complication that can seriously affect the short and long-term prognosis of patients. Sodium thiosulfate has previously been reported to reduce the incidence of acute kidney injury after HIPEC with cisplatin, but this finding has not been confirmed in a high-level study. Therefore, we propose a multi-center, prospective, open-label, randomized, controlled trial including 110 patients with ovarian cancer who received HIPEC with cisplatin, to evaluate whether sodium thiosulfate combined with hydration (55 patients in the trial group) can reduce the incidence of acute kidney injury after HIPEC with cisplatin compared with hydration alone (55 patients in the control group), and to provide high-level evidence for the rationale of using sodium thiosulfate for nephrotoxicity relief in cisplatin HIPEC.

Enrollment: 110 estimated patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:（The following conditions must be met at the same time）

• Patients treated with HIPEC with cisplatin.
• Estimated survival > 12 weeks
• Age from 18 to 70 years
• Bone marrow reserve was well functioning. Leukocytosis ≥ 3.0×10^9/L, neutrophilic granulocyte ≥ 1.5 × 10^9/L, platelet count ≥ 100 × 10^9/L, and hemoglobin ≥ 80 g/L.
• Organs work well. AST ≤ 2.5 × ULN, ALT ≤ 2.5 × upper limit of normal(ULN), total serum bilirubin ≤ 1.5 × ULN, and creatinine ≤ 1.5 × ULN
• ECOG score 0-1
• Patients voluntarily sign an informed consent form

Exclusion Criteria:（None of which was eligible）.

• Extensive abdominal adhesions
• HIPEC with Cisplatin for other medical conditions in the last 5 years.
• Receiving other drugs that cause kidney damage.
• Simultaneous use of amifotin for other diseases.
• Any situation of disease instability or potentially impact safety and adherence of patient.
• Chronic or acute nephropathy of any degree or other serious medical complications.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

HIPEC with sodium thiosulfate and hydration

Experimental group

Description:

Sodium sulfate 9 g/m\^2 combined with 0.9% natrium chloride 150 ml were instilled in 20 min as the time when HIPEC with cisplatin was beginning. After that, sodium sulfate 12 g/m\^2 combined with 0.9% natrium chloride 1000 ml was pumped for 6 h . hydration: On the day of surgery, the day of HIPEC, and 24 hours after HIPEC, daily intravenous rehydration should be performed using natrium chloride, glucose chloride or potassium chloride. The amount of fluid to be replenished should not be less than 3000 milliliters.

Treatment:

Drug: Sodium Sulfate

Drug: Cisplatin

Other: Hydration

HIPEC with hydration only

Active Comparator group

Description:

hydration:On the day of surgery, the day of HIPEC, and 24 hours after HIPEC, daily intravenous rehydration should be performed using natrium chloride, glucose chloride or potassium chloride. The amount of fluid to be replenished should not be less than 3000 milliliters.

Treatment:

Drug: Cisplatin

Other: Hydration