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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4,800
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.
A hemodialysis filter (known as a dialyzer) that is that is widely used across Canada for hemodialysis treatments.
London Health Sciences Centre
London, Ontario, Canada
RECRUITINGPrimary Outcome of All-Cause Mortality
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.
Time frame: From randomization to event (death) or end of treatment (average 2.9 years follow-up), whichever occurs first
Key Secondary Outcome of Cardiovascular and Infection-Related Hospitalizations
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
Time frame: From randomization to the end of treatment (average 2.9 year follow-up)
Cardiovascular-Related Hospitalizations
Time to first and recurrent cardiovascular hospitalizations. Each component of the secondary outcome (cardiovascular-related and infection-related hospitalizations) will be examined separately.
Time frame: From randomization to the end of treatment (average 2.9 year follow-up)
Infection-Related Hospitalizations
Time to first and recurrent infection-related hospitalizations. Each component of the secondary outcome (cardiovascular-related and infection-related hospitalizations) will be examined separately.
Time frame: From randomization to the end of treatment (average 2.9 year follow-up)
Death from Cardiovascular Cause
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.
Time frame: From randomization to end of treatment (average 2.9 year follow-up).
Death from Non-cardiovascular Cause
Death that does not meet the definition for death from a cardiovascular cause.
Time frame: From randomization to end of treatment (average 2.9 year follow-up).
Receipt of a Functional Kidney Transplant
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.
Time frame: From randomization to event (functioning kidney transplant) or end of treatment (average 2.9 years follow-up), whichever comes first.
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