Dialysis for Acute Kidney Failure

(WISDOM Trial)

Recruiting at 2 trial locations

Overseen By Ellen Morrison, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Disqualifiers: End-stage kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different dose levels of a dialysis treatment called Continuous Renal Replacement Therapy (CRRT) for individuals with acute kidney failure in the ICU. Researchers aim to determine if a lower dose of CRRT is as safe and effective as the standard dose, while potentially being more cost-effective. The trial involves two groups: one receiving a low dose and the other receiving the standard dose. Individuals who have recently started CRRT for acute kidney failure and expect to continue it for at least two days may be eligible to join. As an unphased trial, this study allows patients to contribute to important research that could enhance treatment options and cost-effectiveness for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this dialysis method is safe for acute kidney failure patients?

Previous studies have shown that low dose-intensity CRRT (Continuous Renal Replacement Therapy) is safe for patients with sudden kidney failure. Research indicates that removing 10-15 mL of fluid per kilogram of body weight per hour during dialysis is both safe and manageable. This amount is commonly used in medical practice and supported by observational data.

The standard dose-intensity CRRT, which removes 25-30 mL of fluid per kilogram per hour, is also widely used and recommended by medical guidelines. Both dosing methods treat seriously ill patients in intensive care units.

Overall, studies suggest that both low and standard dose-intensity CRRT are safe for patients. No significant adverse events have been reported that would raise concerns about the safety of either treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Continuous Renal Replacement Therapy (CRRT) is unique because it explores a low dose-intensity approach for treating acute kidney failure, aiming to deliver just 10-15 mL/kg/hr. Unlike the standard practice of administering 25-30 mL/kg/hr, this lower dose could offer a safer, more tolerable option for patients. Researchers are excited about the potential to maintain effectiveness while minimizing stress on the patient's body, possibly leading to fewer complications and a more patient-friendly experience.

What evidence suggests that this trial's treatments could be effective for acute kidney failure?

This trial will compare different dose-intensities of Continuous Renal Replacement Therapy (CRRT) for patients with acute kidney failure. Research has shown that more intensive CRRT does not improve outcomes for patients with sudden kidney problems. Studies have found that increasing CRRT intensity does not significantly reduce the risk of death or enhance kidney recovery. Recent trials suggest that lower intensity might be equally effective and could be safer and more cost-effective. Current guidelines recommend lower-intensity CRRT based on this evidence. Using a lower dose of CRRT could be a practical choice without compromising patient safety or outcomes. Participants in this trial will be assigned to either a low dose-intensity arm or a standard dose-intensity arm to further evaluate these findings. ^{1 2 6 7 8}

Who Is on the Research Team?

Ron Wald

Principal Investigator

St. Michael's Hospital (Unity Health)

Sean Bagshaw, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

The WISDOM trial is for adults over 18 years old, weighing at least 55 kg, who are critically ill with acute kidney failure and starting or have started CRRT within the past 24 hours. They should expect to need CRRT for at least 48 hours and be able to consent themselves or through a representative.

Inclusion Criteria

I am expected to undergo CRRT for at least 48 hours.

Able to provide informed consent or have an authorized representative provide consent after being informed on the details and risks of the trial unless a deferred consent process is approved by local Research Ethics Board (REB)

I am starting or have just started CRRT for acute kidney injury.

Exclusion Criteria

My doctor has recommended a higher dose of continuous renal replacement therapy.

I am on regular dialysis for end-stage kidney disease.

Inability to comply with the requirements of the study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low dose-intensity or standard dose-intensity CRRT in the intensive care unit

4 weeks

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including kidney recovery and RRT-free days

90 days

Extension

Optional long-term follow-up to assess extended outcomes and safety

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Continuous Renal Replacement Therapy (CRRT)

Trial Overview This study tests whether a lower dose-intensity of Continuous Renal Replacement Therapy (CRRT) is as effective and safe as the standard higher dose recommended by guidelines for patients with acute kidney injury in intensive care.

How Is the Trial Designed?

Group I: Low dose-intensity Experimental Treatment 1 Intervention

The intervention arm will consist of low dose-intensity CRRT, defined as the hourly delivery of a total effluent of 10-15 mL/kg/hr while receiving CRRT. The intervention dose-intensity is based on the rationale that 10-15 mL/kg/hr is the lower threshold of dose-intensity currently provided in clinical practice and prior observational data showing this threshold is tolerated and safe.

Group II: Standard dose-intensity Active Control 1 Intervention

The control arm will receive a dose-intensity CRRT of 25-30 mL/kg/hr while receiving CRRT, aligned with local practice and information by international clinical practice guidelines. The control dose-intensity is based on the rationale that this is currently recommended in clinical practice guidelines and is commonly applied in routine practice.

Continuous Renal Replacement Therapy (CRRT) is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Continuous Renal Replacement Therapy for:

• Acute kidney injury
• Multiple organ failure
• Sepsis

Approved in United States as Continuous Renal Replacement Therapy for:

• Acute kidney injury
• Multiple organ failure
• Sepsis

Approved in Canada as Continuous Renal Replacement Therapy for:

• Acute kidney injury
• Multiple organ failure
• Sepsis

Approved in Japan as Continuous Renal Replacement Therapy for:

• Acute kidney injury
• Multiple organ failure
• Sepsis

Approved in China as Continuous Renal Replacement Therapy for:

• Acute kidney injury
• Multiple organ failure
• Sepsis

Approved in Switzerland as Continuous Renal Replacement Therapy for:

• Acute kidney injury
• Multiple organ failure
• Sepsis

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

The QUALITY CRRT study is a multicenter evaluation aimed at improving the delivery of continuous renal replacement therapy (CRRT) for critically ill patients, focusing on standardizing practices and monitoring key performance indicators (KPIs) across healthcare systems.

By implementing a structured quality assurance program, the study aims to enhance the effectiveness, safety, and cost-efficiency of CRRT, with outcomes being assessed quarterly to ensure continuous improvement in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the quality of the performance and delivery of continuous renal replacement therapy (CRRT) to critically ill patients across a healthcare system: QUALITY CRRT: a study protocol. Opgenorth, D., Reil, E., Lau, V., et al.[2022]

In a study of 27 septic patients with acute renal failure undergoing continuous renal replacement therapy (CRRT), low levels of antithrombin (AT) were linked to shorter filter lifespans, indicating that AT deficiency contributes to filter clotting issues.

Supplementing antithrombin significantly increased filter lifespan, with continuous infusion showing superior results (48.5 hours) compared to bolus supplementation (27.8 hours), suggesting that monitoring and addressing AT levels could enhance CRRT effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired deficit of antithrombin and role of supplementation in septic patients during continuous veno-venous hemofiltration. Lafargue, M., Joannes-Boyau, O., Honoré, PM., et al.[2008]

Continuous renal replacement therapy (CRRT) is essential for supporting critically ill patients with acute kidney injury, especially those who are hemodynamically unstable, by using various techniques for solute clearance.

The article reviews different CRRT modalities, including hemofiltration, hemodialysis, and hemodiafiltration, and discusses their indications, dosing, and management, highlighting the importance of tailored approaches in renal support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Renal Replacement Therapy: Who, When, Why, and How. Tandukar, S., Palevsky, PM.[2021]

In a study of 64 critically ill patients undergoing continuous renal replacement therapy (CRRT), 25.4% of the analyzed 177 antimicrobial agents were administered at insufficient doses, which could impact treatment effectiveness.

Patients receiving adequate antimicrobial doses had a higher treatment success rate (35.2%) compared to those on low doses (24.0%), highlighting the importance of proper dosing based on drug clearance in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualised antimicrobial dosing in critically ill patients undergoing continuous renal replacement therapy: focus on total drug clearance. Ruiz, J., Favieres, C., Broch, MJ., et al.[2022]

This study aims to create a comprehensive registry of 2000 critically ill patients receiving continuous renal replacement therapy (CRRT) across 4 academic medical centers over 5 years, focusing on variations in CRRT prescription and delivery.

The research will analyze factors such as anticoagulation protocols and fluid overload management to improve patient safety and establish quality measures for CRRT care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRRTnet: a prospective, multi-national, observational study of continuous renal replacement therapy practices. Heung, M., Bagshaw, SM., House, AA., et al.[2022]

In a study of 863 ICU patients undergoing continuous renal replacement therapy (CRRT), in-hospital mortality rates were high, at 61% for those with acute kidney injury (AKI) and 54% for those with end-stage renal disease (ESRD), highlighting the serious risks associated with this treatment.

Only 25% of patients with AKI achieved dialysis-free survival by the end of the study, indicating that while CRRT is a common treatment, its long-term effectiveness in promoting recovery is limited, especially for those with advanced age or comorbid conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study. Allegretti, AS., Steele, DJ., David-Kasdan, JA., et al.[2022]

In a study of 145 acute kidney injury patients undergoing continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA), it was found that RCA is reasonably safe for patients with acute liver dysfunction, provided that circuit time is kept below approximately 50 hours.

The study showed no significant correlations between liver dysfunction markers (total bilirubin and INR) and complications such as electrolyte disturbances or circuit survival time, suggesting that RCA can be effectively managed in these patients with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applying Regional Citrate Anticoagulation in Continuous Renal Replacement Therapy for Acute Kidney Injury Patients with Acute Liver Dysfunction: a Retrospective Observational Study. Yu, Y., Peng, S., Cen, Z., et al.[2018]

The study found that using a countercurrent flow configuration in a hemodiafilter during continuous renal replacement therapy (CRRT) significantly improves solute removal, achieving a clearance of urea at 67.8 ml/min compared to 45.1 ml/min with concurrent flow.

While countercurrent flow enhances solute clearance and convection, the simpler design and handling of concurrent flow may be more beneficial in slow continuous therapies, suggesting that the choice of flow configuration should consider both efficacy and practical treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dialysate flow configurations in continuous renal replacement therapy on solute removal: computational modeling. Kim, JC., Cruz, D., Garzotto, F., et al.[2013]

Continuous renal replacement therapy (CRRT) is essential for supporting critically ill patients, but there is currently limited high-quality evidence to guide individualized treatment plans, including CRRT dose and timing.

Research indicates that while there is potential for tailored CRRT approaches to improve patient outcomes, most current findings are based on observational data, highlighting the need for well-designed randomized trials to better understand patient-specific requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous renal replacement therapy: individualization of the prescription. Haines, RW., Kirwan, CJ., Prowle, JR.[2019]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK556028/

Continuous Renal Replacement Therapy - StatPearls - NCBI CRRT comprises techniques that manage solute removal and fluid balance over 24 hours. CRRT filters blood through a semipermeable membrane using various solute ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6457961/

Intensity of continuous renal replacement therapy for acute ... Based on the current low quality of evidence identified, more intensive CRRT did not demonstrate beneficial effects on mortality or recovery of kidney function ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0902413

Intensity of Continuous Renal-Replacement Therapy in ... In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0034837625001639

Continuous Renal Replacement Therapy: What Have We ... Continuous renal replacement therapy (CRRT) has revolutionized the management of critically ill patients with acute kidney injury (AKI) over the past decade ...

5. journal.chestnet.org journal.chestnet.org/article/S0012-3692(18)32478-4/pdf

Continuous Renal Replacement Therapy - CHEST Journal Continuous renal replacement therapy (CRRT) is commonly used to provide renal support for critically ill patients with acute kidney injury, ...

6. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/cc12780

Continuous renal replacement therapy outcomes in acute ... We analyzed a prospective cohort of all 863 ICU patients initiated on CRRT at an academic medical center from 2008 to 2011 with either new-onset acute kidney ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2590059523000511

Epidemiology and Outcomes of AKI Treated With ... The database has revealed that critically ill patients with acute kidney injury who need CKRT typically have sepsis and require CKRT for fluid management.

8. accp.com accp.com/docs/bookstore/CCSAP/cc2021b2_sample.pdf

Acute Kidney Injury and Continuous Renal Replacement ... Acute kidney injury is a broad term to describe an acute decline in kidney function, often identified based on acute elevations in serum creatinine and/or ...