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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether cilastatin can prevent acute kidney injury (AKI) in hospitalized patients receiving medications that might harm the kidneys. Researchers will compare cilastatin to a placebo to determine its effectiveness in protecting the kidneys. Participants will receive the treatment or placebo every six hours and undergo regular blood tests to monitor kidney function. The trial seeks participants who are currently hospitalized and receiving specific medications that can damage the kidneys, such as certain antibiotics or chemotherapy drugs. As a Phase 2 trial, this research focuses on measuring cilastatin's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that cilastatin is likely to be safe for humans?

Research has shown that cilastatin might protect kidneys from damage. Studies have found that using cilastatin with imipenem results in fewer cases of kidney injury and improved short-term kidney function in at-risk individuals. This suggests cilastatin could be safe and beneficial for those with potential kidney issues.

Cilastatin prevents certain harmful substances from being absorbed by the kidneys, reducing the risk of injury. While most data comes from animal studies and its use with other drugs, cilastatin alone has also shown promise in kidney protection.

Overall, cilastatin appears well-tolerated, and research supports its safety in preventing kidney damage. However, monitoring any treatment closely, especially in a clinical trial setting, remains crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AKI?

Cilastatin is unique because it offers a novel approach to treating acute kidney injury (AKI). While current treatments mainly focus on managing symptoms and preventing further kidney damage, Cilastatin targets renal transporters to reduce the accumulation of harmful substances in kidney cells. This mechanism helps protect the kidneys at a cellular level, potentially preventing injury before it occurs. Researchers are excited about Cilastatin because it could offer a more proactive and protective strategy for AKI, addressing the condition's root cause rather than simply mitigating its effects.

What evidence suggests that cilastatin might be an effective treatment for acute kidney injury?

Research has shown that cilastatin might help prevent sudden kidney problems in people at risk. In this trial, participants in the Cilastatin Intervention arm will receive cilastatin, which blocks certain proteins that allow harmful drugs into kidney cells, thereby reducing damage. Studies found that patients who took imipenem-cilastatin experienced fewer kidney issues and better kidney function, as indicated by lower serum creatinine levels, compared to those who did not take it. In animal studies, cilastatin not only prevented kidney damage but also reduced swelling and improved survival. These findings suggest cilastatin could protect the kidneys of patients taking harmful medications. ^{2 3 6 7 8}

Who Is on the Research Team?

Matthew T James, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39583177/

Nephroprotective Effects of Cilastatin in People at Risk ... Patients treated with imipenem-cilastatin developed AKI less frequently and had lower serum creatinine concentration following treatment ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06886464

Prevention of Nephrotoxin-Induced Acute Kidney Injury ... Through the inhibition of DPEP1 and LRP2, cilastatin has proven effective in preventing tubular drug uptake and kidney injury in cell culture and animal models ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2590059524001249

Nephroprotective Effects of Cilastatin in People at Risk ... Patients treated with imipenem-cilastatin developed AKI less frequently and had lower serum creatinine concentration following treatment than control groups.

4. mdpi.com mdpi.com/1422-0067/26/16/7927

Cilastatin Attenuates Acute Kidney Injury and Reduces ... Cilastatin treatment prevented kidney dysfunction, reduced inflammatory markers, and improved survival by 33%. These results suggest that cilastatin could be a ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.03.06.24303823v1.full-text

Nephroprotective effects of cilastatin in people at risk ... Results from 6 studies showed that imipenem-cilastatin treatment resulted in better kidney function compared to comparators; weighted mean ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11582453/

Nephroprotective Effects of Cilastatin in People at Risk ... Pooled estimates of treatment effects indicated that patients who received imipenem-cilastatin had a lower incidence of AKI and lower serum creatinine ...

7. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/cilastatin_in_the_prevention_and_treatment_of.361.aspx

Cilastatin in the Prevention and Treatment of... Cilastatin, a renal dehydropeptidase-I inhibitor, has demonstrated its usefulness in the protection of AKI induced by nephrotoxic drugs.

8. academic.oup.com academic.oup.com/ofid/article/7/3/ofaa054/5740221

Evaluation of Renal Safety Between Imipenem/Relebactam ... IMI/REL had a more favorable renal safety profile than colistin-based therapy in patients with serious, imipenem-nonsusceptible gram-negative bacterial ...