Using cilastatin to prevent kidney damage from certain hospital medications
The Prevention of Nephrotoxin-Induced Acute Kidney Injury Using Cilastatin (PONTiAK) Trial: A Phase 2B Vanguard Design, Randomized, Double-Blind, Placebo-Controlled Study
PHASE2 · University of Calgary · NCT06886464
This trial will test whether cilastatin can prevent acute kidney injury in hospitalized adults receiving certain kidney-harming medications.
Quick facts
| Phase | PHASE2 |
|---|---|
| Study type | Interventional |
| Enrollment | 698 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Calgary (other) |
| Drugs / interventions | chemotherapy |
| Locations | 2 sites (Calgary, Alberta and 1 other locations) |
| Trial ID | NCT06886464 on ClinicalTrials.gov |
What this trial studies
This Phase 2 randomized, placebo-controlled trial gives hospitalized adults either intravenous cilastatin or a saline placebo every six hours while they are exposed to eligible nephrotoxic drugs and for up to 24 hours after the last exposure. Kidney function will be monitored with daily blood tests during treatment and a follow-up blood test at 90 days, plus a 90-day telephone check-in. The trial targets patients receiving agents such as IV vancomycin, aminoglycosides, calcineurin inhibitors, platinum chemotherapies, or high-risk contrast exposure. The main goal is to see if cilastatin reduces the incidence of nephrotoxin-associated acute kidney injury compared with placebo.
Who should consider this trial
Good fit: Adults (age ≥18) who are hospitalized and receiving eligible IV nephrotoxic medications or high-risk contrast exposure and who can give informed consent (or have a representative who can).
Not a fit: People with advanced kidney failure (eGFR <15 mL/min/1.73 m2), those on maintenance dialysis or with current stage 3 AKI, pregnant or breastfeeding individuals, or those with a known hypersensitivity to imipenem-cilastatin are unlikely to benefit or are excluded.
Why it matters
Potential benefit: If successful, cilastatin could lower the chance of hospital-acquired acute kidney injury, reduce complications and readmissions, and help preserve long-term kidney function.
How similar studies have performed: Preclinical studies and limited early clinical data suggest cilastatin may protect kidneys from some nephrotoxins, but large randomized clinical trial evidence is currently limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * 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.
Where this trial is running
Calgary, Alberta and 1 other locations
- University of Calgary — Calgary, Alberta, Canada (RECRUITING)
- University of Alberta — Edmonton, Alberta, Canada (RECRUITING)
Study contacts
- Principal investigator: Matthew T James, MD — University of Calgary
- Study coordinator: Nusrat S Shommu, PhD
- Email: nsshommu@ucalgary.ca
- Phone: 4032103991
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Acute Kidney Injury, Nephrotoxic, Cilastatin