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

NCT05877911 | Unknown Phase 2

• 1 other identifier: SYSKY-2022-549-02
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Epithelial Ovarian Cancer; Acute Kidney Injury Due to Circulatory Failure

Keywords

Epithelial Ovarian Cancer; Acute Kidney Injury; Hyperthermic Intraperitoneal Chemotherapy; Sodium thiosulfate

Outcome Measures

Primary Outcomes (1)

• 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.

  Within one week after patients receive cisplatin-based HIPEC.

Secondary Outcomes (3)

• 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.

Study Arms (2)

HIPEC with sodium thiosulfate and hydration

EXPERIMENTAL

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; Other: Hydration; Drug: Cisplatin

HIPEC with hydration only

ACTIVE COMPARATOR

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

Interventions

Sodium Sulfate DRUG

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.

HIPEC with sodium thiosulfate and hydration

Hydration OTHER

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.

HIPEC with hydration only; HIPEC with sodium thiosulfate and hydration

Cisplatin DRUG

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.

HIPEC with hydration only; HIPEC with sodium thiosulfate and hydration

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Yunnan Cancer Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator

Related Publications (19)

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  PMID: 32689832 RESULT

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Acute Kidney Injury

Interventions

sodium sulfate; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Jing Li, Doctor

CONTACT

15915893493; lijing228@mail.sysu.edu.cn

Yuting Lai, Undergraduate

CONTACT

18797871751; laiyuting0128@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: May 26, 2023
• Study Start: May 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: April 1, 2025
• Last Updated: May 26, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share