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

Primary Purpose

Epithelial Ovarian Cancer, Acute Kidney Injury Due to Circulatory Failure

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sodium Sulfate
Hydration
Cisplatin
Sponsored by
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring Epithelial Ovarian Cancer, Acute Kidney Injury, Hyperthermic Intraperitoneal Chemotherapy, Sodium thiosulfate

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    HIPEC with sodium thiosulfate and hydration

    HIPEC with hydration only

    Arm 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.

    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.

    Outcomes

    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.
    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.
    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.
    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).
    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.

    Full Information

    First Posted
    April 3, 2023
    Last Updated
    May 17, 2023
    Sponsor
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Collaborators
    Yunnan Cancer Hospital, Qilu Hospital of Shandong University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05877911
    Brief Title
    Effect of Sodium Thiosulfate on Nephrotoxicity of Cisplatin Intraperitoneal Heat-perfusion Chemotherapy
    Official Title
    Effect of Sodium Thiosulfate on Nephrotoxicity of Cisplatin Intraperitoneal Heat-perfusion Chemotherapy: a Multi-center Prospective Randomized Controlled Trial.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 2023 (Anticipated)
    Primary Completion Date
    January 2025 (Anticipated)
    Study Completion Date
    April 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Collaborators
    Yunnan Cancer Hospital, Qilu Hospital of Shandong University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Epithelial Ovarian Cancer, Acute Kidney Injury Due to Circulatory Failure
    Keywords
    Epithelial Ovarian Cancer, Acute Kidney Injury, Hyperthermic Intraperitoneal Chemotherapy, Sodium thiosulfate

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    110 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    HIPEC with sodium thiosulfate and hydration
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    HIPEC with hydration only
    Arm Type
    Active Comparator
    Arm 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Sodium Sulfate
    Intervention Description
    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.
    Intervention Type
    Other
    Intervention Name(s)
    Hydration
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Calculate the incidence of acute kidney injury after HIPEC based on creatinine levels and 24-hour urine output according to KDIGO criteria.
    Description
    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.
    Time Frame
    Within one week after patients receive cisplatin-based HIPEC.
    Secondary Outcome Measure Information:
    Title
    Calculate the incidence of chronic kidney injury after HIPEC based on creatinine levels according to KDIGO criteria.
    Description
    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.
    Time Frame
    Through study completion, an average of 2 year
    Title
    Number of patients with sodium sulfate-related adverse events assessed by CTCAE v5.0.
    Description
    To investigate adverse events associated with sodium sulfate. The Adverse events were evaluated and graded according to CTCAE5.0
    Time Frame
    72 hours after sodium sulfate administration.
    Title
    Time from randomization to relapse or death(DFS).
    Description
    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.
    Time Frame
    From date of randomisation to date of first recorded progression or death from any cause, whichever came first, assessed up to 5 years.

    10. Eligibility

    Sex
    Female
    Accepts Healthy Volunteers
    No
    Eligibility 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jing Li, Doctor
    Phone
    15915893493
    Email
    lijing228@mail.sysu.edu.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yuting Lai, Undergraduate
    Phone
    18797871751
    Email
    laiyuting0128@163.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No
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    Effect of Sodium Thiosulfate on Nephrotoxicity of Cisplatin Intraperitoneal Heat-perfusion Chemotherapy

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