To compare cilastatin vs thiosulfatein renal protection in patients undergoing debulking surgery with intraoperative hyperthermic intraperitoneal chemotherapy with cisplatin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

19 Dec 2024 → ongoing

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518854-18-00

EudraCT number

2022-001417-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Non inferiority study of cilastatin versus Thiosulfate in reducing acute kidney damage (days 1-7) (creatinine levels and KDIGO scale) in patients treated with CRS+HIPEC-cisplatin during the immediate postoperative period.

Secondary objectives 6

1. To study the pharmacokinetics of cisplatin with cilastatin with thiosulfate during the HIPEC procedure.
2. To analyze the number of subjects presenting adverse events and serious adverse events during a follow-up period of 30 days
3. To observe the evolution of ARF in patients with cilastatin/thiosulfate with a total follow-up of 14 days.
4. Evaluation of preoperative, intraoperative and postoperative factors that influence renal damage in CRS+HIPEC–cisplatin
5. To study the usefulness of the determination of urinary H202 in the prediction of the appearance of DR by cisplatin after the HIPEC procedure.
6. To study the changes in urinary FasL after the HIPEC procedure as an early measure of DR intensity, as well as the specificity of the mechanism of action of the nephroprotection expected with cilastatin.

Conditions and MedDRA coding

acute kidney injury

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age: adult patients from 18-75 years
2. Sex: Male/Female
3. Eastern Cooperative Oncology Group Performance status (ECOG PS) # 2
4. General situation of the patient: patient suitable for major surgery, with values of creatinine, bilirubin, blood series in a range close to normal (Hb>10g/dl, leucos >3000/ml, neutrals >1000/ml, platelets >100,000 /ml).
5. Patients evaluated in the Anesthesia office and considered suitable for the intervention
6. Signed informed consent
7. Disease confined to the abdomen: CRS+HIPEC is not contemplated in patients with lung or bone metastases, etc.
8. Evaluation in a Multidisciplinary Committee: radiological PCI is performed and it is estimated possibilities of complete cytoreduction, indicating CRS + HIPEC.

Exclusion criteria 6

1. Non-acceptance to participate in the clinical trial.
2. ECOG PS > 2.
3. Not suitable for major surgery.
4. Disease not limited to the abdomen or with signs that it cannot be optimally cytoreduced (intestinal obstruction, biliary obstruction, ureteral obstruction, diffuse involvement of the small intestine or mesentery).
5. Allergy to platinum.
6. Patients with a neurological history who in the investigator's opinion are at risk of seizures associated with imipenem/cliastatin treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients with renal failure at 7 days* (if there is renal damage, follow-up until postoperative day 14) measured through creatinine values and the KDIGO classification. Renal failure is defined as an increase in serum creatinine of 1.5 to 1.9 times baseline, or an increase in serum creatinine by #0.3 mg/dL (#26.5 μmol/L), or a decrease in urine output <0.5 mL/kg/hour for 6 to 12 hours.

Secondary endpoints 7

1. Differences in plasma pharmacokinetic variables of cisplatin during the HIPEC procedure between cilastatin-treated and thiosulfate-treated patients
2. Percentage of patients experiencing serious adverse events, adverse events related to study treatment, and adverse events occurring during the study.
3. Comparison of ARF in patients with cilastatin or thiosulfate with a total follow-up of 14 days
4. Comparison of urinary H202 values between patients who suffer from DR and patients who do not suffer from it.
5. Comparison of urinary H202 values between patients who suffer DR and patients who do not.
6. Comparison of preoperative, intraoperative and postoperative factors between patients who suffer from kidney damage and patients who do not.
7. Comparison of urinary FasL between patients with renal damage and patients without.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Address

Calle Del Doctor Esquerdo 46

City

Madrid

Postcode

28007

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Contact name

Maria Carmen de la Cruz Arguedas

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Contact name

Maria Carmen de la Cruz Arguedas

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications