DIALysis With EXpanded Solute Removal

Official title

DIALysis With EXpanded Solute Removal (DIALEX): A Large, Simple Randomized Trial to Evaluate the Major Health Effects of Expanded Versus Conventional Hemodialysis.

Overview

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).

Interventions

• Device Super High-Flux Dialyzer
  A hemodialysis filter (known as a dialyzer) that is currently approved by Health Canada and available for use across Canada. This filter has larger pores than a high-flux dialyzer that allow for greater removal of potential toxins and wastes in the blood that would regularly be filtered out by healthy kidneys.
• Device High-Flux Dialyzer
  A hemodialysis filter (known as a dialyzer) that is that is widely used across Canada for hemodialysis treatments.

Primary outcome measures

• Primary Outcome of All-Cause Mortality [Time frame: From randomization to event (death) or end of treatment (average 2.9 years follow-up), whichever occurs first]

Secondary outcome measures (6)

• Key Secondary Outcome of Cardiovascular and Infection-Related Hospitalizations [Time frame: From randomization to the end of treatment (average 2.9 year follow-up)]
• Cardiovascular-Related Hospitalizations [Time frame: From randomization to the end of treatment (average 2.9 year follow-up)]
• Infection-Related Hospitalizations [Time frame: From randomization to the end of treatment (average 2.9 year follow-up)]
• Death from Cardiovascular Cause [Time frame: From randomization to end of treatment (average 2.9 year follow-up).]
• Death from Non-cardiovascular Cause [Time frame: From randomization to end of treatment (average 2.9 year follow-up).]
• Receipt of a Functional Kidney Transplant [Time frame: From randomization to event (functioning kidney transplant) or end of treatment (average 2.9 years follow-up), whichever comes first.]

Eligibility criteria

Inclusion Criteria: Inclusion requires that all the following are present:

• One of:

• Age 60 years or older; or
• Age 45 to 59 years with a history of diabetes mellitus (Type 1 or Type 2) regardless of current glycemic status; and
• Receiving any form of dialysis regularly for the previous 90 days; and
• Currently receiving HD in-centre (main or satellite unit) 3 or more times per week; and
• A valid provincial or territorial health insurance card number.

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

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

• Known or anticipated intolerance to the Nipro Elisio HX dialyzer; or
• Planned to receive HDF; or
• Planned to receive nocturnal HD; or
• 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
• Anticipated severe non-adherence to the frequency or duration of prescribed dialysis treatment; or
• An overriding clinical preference for expanded HD (i.e., dialysis with the Elisio HX or other comparable dialyzer, such as Baxter TheranovaTM); or
• Another medical, psychosocial, or logistical reason; or
• 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
• Previously enrolled in this trial; or
• Declined participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• London Health Sciences Centre — London

Identifiers

NCT: NCT06660277 · 4954 · R-25-209

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗