Effect of Sodium Thiosulfate on Nephrotoxicity of Cisplatin Intraperitoneal Heat-perfusion Chemotherapy: a Multi-center Prospective Randomized Controlled Trial.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 110
- 主要终点
- Calculate the incidence of acute kidney injury after HIPEC based on creatinine levels and 24-hour urine output according to KDIGO criteria.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •（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
排除标准
- •（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.
研究组 & 干预措施
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.
干预措施: Sodium Sulfate (Drug)
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.
干预措施: Hydration (Other)
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.
干预措施: Cisplatin (Drug)
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.
干预措施: Hydration (Other)
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.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Calculate the incidence of acute kidney injury after HIPEC based on creatinine levels and 24-hour urine output according to KDIGO criteria.
时间窗: 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.
次要结局
- 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)
- Number of patients with sodium sulfate-related adverse events assessed by CTCAE v5.0.(72 hours after sodium sulfate administration.)
- 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.)