Dialysis for Acute Kidney Failure

(WISDOM Trial)

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

Trial Summary

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 data supports the effectiveness of the treatment Continuous Renal Replacement Therapy (CRRT) for acute kidney failure?

Continuous Renal Replacement Therapy (CRRT) is widely used in intensive care units for patients with acute kidney injury, especially those who are critically ill and have unstable blood pressure. It is considered the main form of dialysis for these patients, although there is variability in how it is prescribed and delivered. ^{1 2 3 4 5}

Is continuous renal replacement therapy (CRRT) safe for humans?

Continuous renal replacement therapy (CRRT) is commonly used and recommended for critically ill patients with acute kidney injury, especially those who are hemodynamically unstable (have unstable blood pressure). While the studies highlight variability in how CRRT is delivered, they do not report specific safety concerns, suggesting it is generally considered safe when used appropriately in a clinical setting. ^{3 4 6 7 8}

How is Continuous Renal Replacement Therapy (CRRT) different from other treatments for acute kidney failure?

Continuous Renal Replacement Therapy (CRRT) is unique because it provides continuous dialysis support for critically ill patients who are hemodynamically unstable (have unstable blood pressure), using techniques that can clear waste through different methods like filtration and diffusion, unlike traditional intermittent dialysis which is done in sessions. ^{3 4 6 8 9}

What is the purpose of this trial?

An estimated 10-15% of critically ill patients with acute kidney failure in the intensive care unit receive acute dialysis therapy. The majority of these patients initially receive a continuous form of dialysis therapy call continuous renal replacement therapy (CRRT). Prior studies have suggested that higher CRRT dose-intensity improved health outcomes for these patients; however, this was not found in high-quality clinical trials. These more recent trials suggested a lower range of dose-intensity compared with the higher range as the new standard of care. This was incorporated into guidelines. To date, no clinical trials have evaluated this lower range and specifically, it is plausible that an even lower dose-intensity of CRRT may be well tolerated, safe, associated with similar outcomes and be more cost-effective. This is the objective of the WISDOM trial, to compare the guideline standard with lower dose-intensity among patients who are started on CRRT in the intensive care unit.

Research Team

Ron Wald

Principal Investigator

St. Michael's Hospital (Unity Health)

Sean Bagshaw, MD

Principal Investigator

University of Alberta

Eligibility Criteria

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.

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

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)

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study. [2022]

3. England 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. [2022]

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

CRRTnet: a prospective, multi-national, observational study of continuous renal replacement therapy practices. [2022]

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

Continuous renal replacement therapy: individualization of the prescription. [2019]

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

Continuous Renal Replacement Therapy: Who, When, Why, and How. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of dialysate flow configurations in continuous renal replacement therapy on solute removal: computational modeling. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Individualised antimicrobial dosing in critically ill patients undergoing continuous renal replacement therapy: focus on total drug clearance. [2022]

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

Acquired deficit of antithrombin and role of supplementation in septic patients during continuous veno-venous hemofiltration. [2008]