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

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05877911

Collaborator

Yunnan Cancer Hospital (Other), Qilu Hospital of Shandong University (Other)

110

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer Acute Kidney Injury Due to Circulatory Failure	Drug: Sodium Sulfate Other: Hydration Drug: Cisplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients were randomly assigned to treatment group or control group by block randomisation in a 1:1 ratio. Treatment group: Receive HIPEC using sodium thiouracil and hydration Control group: Receive HIPEC only using hydration.Patients were randomly assigned to treatment group or control group by block randomisation in a 1:1 ratio. Treatment group: Receive HIPEC using sodium thiouracil and hydration Control group: Receive HIPEC only using hydration.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Sodium Thiosulfate on Nephrotoxicity of Cisplatin Intraperitoneal Heat-perfusion Chemotherapy: a Multi-center Prospective Randomized Controlled Trial.

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HIPEC with sodium thiosulfate and hydration 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.	Drug: Sodium Sulfate 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. Other: 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. Drug: Cisplatin Infuse cisplatin (75mg/m^2) at 43℃ through the two drainage tubes placed in the upper abdomen, using the two drainage tubes placed in the lower abdomen as the effluent tubes, with an infusion time of 60-90 minutes and an infusion rate of 500-600 mL/min. The first HIPEC should be performed within 24-48 hours after cytoreductive surgery. The second HIPEC should be performed 24 hours after the completion of the first HIPEC. Intravenous sedatives such as dexmedetomidine or propofol at 2-6 ml/h should be administered during HIPEC treatment with continuous intravenous infusion by a pump，or intramuscular injection of 50 mg of pethidine.
Active Comparator: HIPEC with hydration only 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.	Other: 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. Drug: Cisplatin Infuse cisplatin (75mg/m^2) at 43℃ through the two drainage tubes placed in the upper abdomen, using the two drainage tubes placed in the lower abdomen as the effluent tubes, with an infusion time of 60-90 minutes and an infusion rate of 500-600 mL/min. The first HIPEC should be performed within 24-48 hours after cytoreductive surgery. The second HIPEC should be performed 24 hours after the completion of the first HIPEC. Intravenous sedatives such as dexmedetomidine or propofol at 2-6 ml/h should be administered during HIPEC treatment with continuous intravenous infusion by a pump，or intramuscular injection of 50 mg of pethidine.

Arm

Intervention/Treatment

Experimental: HIPEC with sodium thiosulfate and hydration

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.

Drug: Sodium Sulfate

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.

Other: 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.

Drug: Cisplatin

Infuse cisplatin (75mg/m^2) at 43℃ through the two drainage tubes placed in the upper abdomen, using the two drainage tubes placed in the lower abdomen as the effluent tubes, with an infusion time of 60-90 minutes and an infusion rate of 500-600 mL/min. The first HIPEC should be performed within 24-48 hours after cytoreductive surgery. The second HIPEC should be performed 24 hours after the completion of the first HIPEC. Intravenous sedatives such as dexmedetomidine or propofol at 2-6 ml/h should be administered during HIPEC treatment with continuous intravenous infusion by a pump，or intramuscular injection of 50 mg of pethidine.

Active Comparator: HIPEC with hydration only

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.

Other: Hydration

Drug: Cisplatin

Outcome Measures

Primary Outcome Measures

Calculate the incidence of acute kidney injury after HIPEC based on creatinine levels and 24-hour urine output according to KDIGO criteria. [Within one week after patients receive cisplatin-based HIPEC.]
To determine whether the use of sodium sulfate combined with hydration reduces the incidence of acute kidney injury (KDIGO criteria grade 1-3) effectively in the intention to treat population compared with hydration alone in patients receiving HIPEC with cisplatin (75mg/m^2,43 °C,90 minutes) according to creatinine levels and 24-hour urine.

Secondary Outcome Measures

Calculate the incidence of chronic kidney injury after HIPEC based on creatinine levels according to KDIGO criteria. [Through study completion, an average of 2 year]
To determine whether the use of sodium sulfate combined with hydration reduces the incidence of chronic kidney injury effectively in the intention to treat population compared with hydration alone in patients receiving HIPEC with cisplatin (75mg/m^2,43 °C,90 minutes) according to creatinine levels.
Number of patients with sodium sulfate-related adverse events assessed by CTCAE v5.0. [72 hours after sodium sulfate administration.]
To investigate adverse events associated with sodium sulfate. The Adverse events were evaluated and graded according to CTCAE5.0
Time from randomization to relapse or death（DFS）. [From date of randomisation to date of first recorded progression or death from any cause, whichever came first, assessed up to 5 years.]
Time from randomization to relapse or death. The diagnosis of disease recurrence includes CA125 more than two times the minimum value, as specified by the Gynecologic Cancer International Collaborative Group (GCIG), or according to the RECIST v1.1 criteria. Any one of the above two criteria is met first, then the tumor is recurrent.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.