RecruitingPhase 2NCT06886464

Prevention of Nephrotoxin-Induced Acute Kidney Injury Using Cilastatin

The Prevention of Nephrotoxin-Induced Acute Kidney Injury Using Cilastatin (PONTiAK) Trial: A Phase 2B Vanguard Design, Randomized, Double-Blind, Placebo-Controlled Study

Sponsor

Matthew James

Enrollment

698 participants

Start Date

Jul 16, 2025

Study Type

INTERVENTIONAL

Conditions

Acute Kidney Injury

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

Eligibility

Min Age: 18 Years

Inclusion Criteria3

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.

Exclusion Criteria8

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.