Cilastatin for Acute Kidney Injury

(PONTiAK Trial)

Recruiting at 1 trial location

Overseen By Nusrat S Shommu, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Matthew James

Must be taking: Nephrotoxic medications

Must not be taking: Imipenem-cilastatin, Probenecid

Disqualifiers: Stage 3 AKI, G5 CKD, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 hours

698 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are actively receiving certain nephrotoxic medications. If you are taking imipenem-cilastatin or probenecid, you must stop at least 48 hours before joining the trial.

How does the drug cilastatin differ from other treatments for acute kidney injury?

Cilastatin is unique because it protects the kidneys from damage caused by certain drugs like gentamicin and cisplatin without affecting their effectiveness. It works by preventing harmful substances from entering kidney cells and reducing cell damage, making it a novel option for preventing drug-induced kidney injury. ^{1 2 3 4 5}

What is the purpose of this trial?

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

Research Team

Matthew T James, MD

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for hospitalized patients at risk of acute kidney injury due to nephrotoxic medications. Participants must be able to receive intravenous treatments and commit to daily blood tests for kidney function, a follow-up test, and a telephone survey 90 days after starting the trial.

Inclusion Criteria

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

I am currently on medication that could harm my kidneys.

Exclusion Criteria

Pregnancy or lactation

Known hypersensitivity to imipenem-cilastatin

Treatment with another investigational medicinal product or participation in another interventional Study within 30 days

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive IV cilastatin or placebo every 6 hours for up to 24 hours after last exposure to nephrotoxic medication

Up to 24 hours

Daily visits during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up blood test and telephone survey at 90 days after randomization

90 days

1 follow-up blood test, 1 telephone survey

Extended Follow-up

Participants' major adverse kidney and cardiovascular outcomes are monitored via administrative data linkage

2 years

Treatment Details

Interventions

• Cilastatin

Trial Overview The study is testing whether cilastatin can prevent acute kidney injury in patients exposed to harmful medications. It involves comparing cilastatin given intravenously every 6 hours against a saline placebo, with both groups monitored closely for changes in kidney function.

Participant Groups

Group I: Cilastatin Intervention Experimental Treatment 1 Intervention

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

Group II: Placebo Control Placebo Group 1 Intervention

Patients in this Arm will receive placebo

Who Is Running the Clinical Trial?

Matthew James

Lead Sponsor

Trials

1

Recruited

700+

Alberta Health services

Collaborator

Trials

168

Recruited

658,000+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

The therapeutic effect of Cilastatin on drug-induced nephrotoxicity: a new perspective. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Inhibition of brush border dipeptidase with cilastatin reduces toxic accumulation of cyclosporin A in kidney proximal tubule epithelial cells. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Cilastatin protects against tacrolimus-induced nephrotoxicity via anti-oxidative and anti-apoptotic properties. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats. [2022]