Prevention of Nephrotoxin-Induced Acute Kidney Injury Using Cilastatin

NCT06886464 | Recruiting Phase 2 DMC

• 1 other identifier: NEPH24-1191
• Study Type: interventional
• Target: 698
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to repurpose cilastatin for preventing acute kidney injury (AKI) in hospitalized patients receiving nephrotoxic medications. The trial will evaluate the efficacy of the re-purposed drug. The main questions it aims to answer are: \- whether cilastatin will prevent nephrotoxic AKI in hospitalized patients. Researchers will compare the drug cilastatin to a placebo (a look-alike substance that contains no drug) to see if drug cilastatin works to prevent AKI in hospitalized patients receiving nephrotoxic medications. Participants will:

• Receive drug Cilastatin or a placebo intravenously every 6 hours for up to 24 hours after last exposure to nephrotoxic medication
• Have blood test for kidney function every day they are on treatment.
• Have a follow-up blood test at 90 days after randomization
• Have a telephone survey at 90 days after randomization

Conditions

Acute Kidney Injury

Keywords

Acute Kidney Injury; Nephrotoxic; Cilastatin

Outcome Measures

Primary Outcomes (1)

• Number of participants developing AKI

  Evaluation of Acute Kidney Injury (AKI) according to KDIGO serum creatinine (SCr) criteria; ≥ 26 mmol/L (0.3 mg/dL) increase in SCr within 48 hours or ≥50% increase in SCr within 7 days

  7 days after administration of a nephrotoxic medication

Secondary Outcomes (9)

• Number of participants developing stage-1, stage-2, and stage-3 AKI

  Within 30 days of administration of nephrotoxic medication

• Number of participants needing dialysis

  Within 30 days of administration of nephrotoxic medication

• Number of days admitted to hospital

  Within 30 days of receiving nephrotoxic medication

• Measurement of eGFR and Cystatin C

  90 days from study enrollment.

• Number of participants with SCr 1.5 times less than baseline

  90 days from study enrollment.

Other Outcomes (2)

• Number of participants developing Major Adverse Kidney Event (MAKE)

  2 years from study enrollment

• Major Adverse Cardiovascular Endpoint (MACE)

  2 years from study enrollment

Study Arms (2)

Cilastatin Intervention

EXPERIMENTAL

Patients in this Arm will receive the Investigational Medicinal Product- Cilastatin

Drug: Cilastatin Sodium

Placebo Control

PLACEBO COMPARATOR

Patients in this Arm will receive placebo

Drug: Placebo-Saline

Interventions

Cilastatin Sodium DRUG

Intravenous cilastatin reconstituted in normal saline solution

Also known as: Renal dehydropeptidase inhibitor

Cilastatin Intervention

Placebo-Saline DRUG

Identical looking normal saline solution

Also known as: Control

Placebo Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Active treatment with an eligible nephrotoxic medication- IV vancomycin, IV aminoglycoside (gentamicin or tobramycin), IV calcineurin inhibitor (cyclosporine or tacrolimus), or IV or intraperitoneal platin-based chemotherapy or ifosfamide; or intraarterial radiographic contrast with two or more high-risk nephrotoxic medication exposures according to the NINJA algorithm.
• Able to provide informed consent or have an authorized representative available and willing to give written informed consent after being properly informed of the nature and risks of the Study.

You may not qualify if:

• Stage 3 AKI based on Kidney Disease Improving Global Outcomes (KDIGO) SCr or urine output criteria, or receipt of short-term dialysis.
• Category G5 CKD (defined as a CKD-EPI eGFR or \<15 mL/min/1.73 m2) or being treated with maintenance dialysis or a kidney transplant.
• Pregnancy or lactation
• Known hypersensitivity to imipenem-cilastatin.
• Active or recent treatment (within 48 hours) with imipenem-cilastatin
• Active or recent treatment (within 48 hours) with probenecid (medication used for gout prevention that inhibits cilastatin excretion and decreases plasma clearance)
• Treatment with another investigational medicinal product or participation in another interventional Study within 30 days
• Inability to comply with the requirements of the Study protocol.

Sponsors & Collaborators

• Matthew James: lead
• Alberta Health services: collaborator
• University of Alberta: collaborator

Study Sites (2)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

RECRUITING

Related Publications (2)

• Elliott MJ, Fiest KM, Love S, Birdsell D, Loth M, Dumka H, Rana B, Shommu N, Benterud E, Gil S, Acharya D, Harrison TG, Pannu N, James MT. Patient Preferences and Priorities for the Design of an Acute Kidney Injury Prevention Trial: Findings from a Consensus Workshop. Kidney360. 2024 Oct 1;5(10):1455-1465. doi: 10.34067/KID.0000000000000554. Epub 2024 Aug 15.

  PMID: 39146029 BACKGROUND

• Acharya D, Ghanim F, Harrison TG, Scory TD, Shommu N, Ronksley PE, Elliott MJ, Collister D, Pannu N, James MT. Nephroprotective Effects of Cilastatin in People at Risk of Acute Kidney Injury: A Systematic Review and Meta-analysis. Kidney Med. 2024 Oct 11;6(12):100913. doi: 10.1016/j.xkme.2024.100913. eCollection 2024 Dec.

  PMID: 39583177 BACKGROUND

Related Links

• Alberta Health Services Connect Care.

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Cilastatin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• Matthew T James, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nusrat S Shommu, PhD

CONTACT

4032103991; nsshommu@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 20, 2025
• Study Start: July 16, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)