DIALysis With EXpanded Solute Removal

Not Applicable

Recruiting

• Conditions: Kidney Failure, Chronic; Chronic Kidney Disease Requiring Hemodialysis; End-Stage Kidney Disease (ESKD); Chronic Kidney Disease Requiring Chronic Dialysis; Pragmatic Randomized Controlled Trial; Renal Insufficiency, Chronic; Kidney Disease; Hemodialysis

• Registration Number: NCT06660277
• Lead Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Brief Summary

The goal of this clinical trial is to evaluate the health effects of expanded hemodialysis in patients receiving hemodialysis. The main question it aims to answer is:

1\) Does expanded hemodialysis reduce the risk of death from any cause?

Researchers will compare expanded hemodialysis to conventional hemodialysis (the treatment currently used for the majority of patients receiving hemodialysis) to see if expanded hemodialysis works to improve patient outcomes.

Participants will continue to receive their regularly scheduled hemodialysis treatments using either a super high-flux/expanded dialysis filter or a high-flux/conventional dialysis filter. All other aspects of treatments remain the same. No additional tests or visits are required. Data will be obtained using administrative healthcare databases and medical record review (at a subset of participating locations).

Detailed Description

Background:

Expanded hemodialysis refers to hemodialysis treatment using a newer generation of hemodialysis filters or "dialyzers" that remove large middle molecules to a greater extent than conventional "high-flux" dialyzers. This is expected to improve major health outcomes. However, despite a decade of availability and promising surrogate data from small trials and patient outcomes data from large observational studies, dialyzers capable of providing expanded hemodialysis have failed to achieve significant adoption conventional high-flux dialyzers in the absence of more definitive evidence. A large, rigorous randomized controlled trial is necessary to establish the clinical effectiveness of expanded hemodialysis compared to conventional hemodialysis with high-flux dialyzers.

Study Design:

Parallel, block randomized, controlled, open label, superiority trial comparing the clinical effects of expanded hemodialysis using Nipro Elisio HX dialyzers to conventional hemodialysis using high-flux dialyzers. The allocation ratio will vary between 1:3 or 1:1 ratio depending on their dialysis unit.

Setting:

Community and academic hemodialysis facilities.

Study Size:

4800 participants (1200 in expanded hemodialysis arm and 3600 in conventional high-flux hemodialysis arm) followed for a mean of 2.9 years.

Trial Duration:

Duration of participant accrual - 2 years from date of first participant recruited.

Total duration - 5 years from date of first participant recruited. Trial results anticipated to be announced in 2030.

Study Power:

90% power to detect 15% relative reduction in the hazard of death (hazard ratio 0.85).

Study Timeline

• Study First Submitted: 2024-10-23
• Study First Submitted QC: 2024-10-23
• Study First Posted: 2024-10-28
• Status Verified: 2025-08
• Study Start: 2025-08-12
• Last Update Submitted: 2025-08-22
• Last Update Posted: 2025-08-28
• Primary Completion: 2030-08
• Study Completion: 2030-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4800

Inclusion Criteria

Inclusion requires that all the following are present:

1. One of:

   1. Age 60 years or older; or
   2. Age 45 to 59 years with a history of diabetes mellitus (Type 1 or Type 2) regardless of current glycemic status; and

2. Receiving any form of dialysis regularly for the previous 90 days; and

3. Currently receiving HD in-centre (main or satellite unit) 3 or more times per week; and

4. A valid provincial or territorial health insurance card number.

Exclusion Criteria

Patients are ineligible if they meet any of the following criteria:

1. Not appropriate for this study in the opinion of the treating nephrologist or dialysis nurse practitioner due to any of:

   1. Known or anticipated intolerance to the Nipro Elisio HX dialyzer; or
   2. Planned to receive HDF; or
   3. Planned to receive nocturnal HD; or
   4. Anticipated to discontinue in-centre HD in the next 3 months for any reason (examples: palliation, transplantation, home dialysis, recovery of kidney function, death, others); or
   5. Anticipated severe non-adherence to the frequency or duration of prescribed dialysis treatment; or
   6. An overriding clinical preference for expanded HD (i.e., dialysis with the Elisio HX or other comparable dialyzer, such as Baxter TheranovaTM); or
   7. Another medical, psychosocial, or logistical reason; or

2. Enrolled in another clinical trial that explicitly prohibits concurrent participation in other clinical trials or that would substantially interfere with adherence to the DIALEX procedures (note that DIALEX otherwise permits concurrent participation in other trials); or

3. Previously enrolled in this trial; or

4. Declined participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Primary Outcome of All-Cause Mortality	From randomization to event (death) or end of treatment (average 2.9 years follow-up), whichever occurs first	Outcome data will be collected as a result of routine patient interactions with the healthcare system and will be obtained from national and provincial data repositories (with the exceptions of routine care symptoms and ESA utilization outcomes, in participating sites), enabling health records to be analyzed in a privacy-compliant manner. These datasets have high levels of completeness and validity. The primary outcome, all-cause mortality, is captured with over 99% accuracy in our data sources.

Secondary Outcome Measures

Name	Time	Method
Key Secondary Outcome of Cardiovascular and Infection-Related Hospitalizations	From randomization to the end of treatment (average 2.9 year follow-up)	The key secondary outcome will be time to first and recurrent cardiovascular or infection-related hospitalizations. Cardiovascular and infection-related hospitalizations will be ascertained using primary discharge ICD-10 diagnosis codes in the Canadian Institute for Health Information Discharge Abstract Database
Cardiovascular-Related Hospitalizations	From randomization to the end of treatment (average 2.9 year follow-up)	Time to first and recurrent cardiovascular hospitalizations. Each component of the secondary outcome (cardiovascular-related and infection-related hospitalizations) will be examined separately.
Infection-Related Hospitalizations	From randomization to the end of treatment (average 2.9 year follow-up)	Time to first and recurrent infection-related hospitalizations. Each component of the secondary outcome (cardiovascular-related and infection-related hospitalizations) will be examined separately.
Death from Cardiovascular Cause	From randomization to end of treatment (average 2.9 year follow-up).	Defined as any out-of-hospital death or death that occurred during a hospitalization for a cardiovascular cause captured in Canada in the CIHI-DAD database.
Death from Non-cardiovascular Cause	From randomization to end of treatment (average 2.9 year follow-up).	Death that does not meet the definition for death from a cardiovascular cause.
Receipt of a Functional Kidney Transplant	From randomization to event (functioning kidney transplant) or end of treatment (average 2.9 years follow-up), whichever comes first.	Receipt of a functional kidney transplant is defined, in Canada, by a record of a hospital admission in the CIHI-DAD database with an ICD-10 code for kidney transplantation followed by discontinuation of dialysis in the absence of death. Receipt of a functioning kidney transplant refers to the first functioning transplant received after randomization.

Trial Locations

Locations (1)

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada