DIALysis With EXpanded Solute Removal (DIALEX)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Renal Insufficiency, Chronic; Hemodialysis; Kidney Failure, Chronic; Kidney Disease; Pragmatic Randomized Controlled Trial; Chronic Kidney Disease Requiring Chronic Dialysis; Chronic Kidney Disease Requiring Hemodialysis; End-Stage Kidney Disease (ESKD)
• Intervention / Treatment: Device: Super High-Flux Dialyzer; Device: High-Flux Dialyzer

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 Type: Interventional
• Enrollment (Estimated): 4800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pavel S Roshanov, MD MSc FRCPC; Phone Number: 519-663-3350; Email: pavel.roshanov@lhsc.on.ca
• Study Contact Backup: Name: Central Research Coordinator; Email: fixdialysis@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Centre
      • Contact: Pavel S Roshanov, MD MSc FRCPC; Phone Number: 519-663-3350; Email: pavel.roshanov@lhsc.on.ca
      • Contact: Central Research Coordinator; Email: fixdialysis@lhsc.on.ca
      • Principal Investigator: Pavel S Roshanov, MD MSc FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Expanded Hemodialysis; Participants will receive their regularly scheduled hemodialysis treatments using a super high-flux dialyzer (Nipro Elisio HX).	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.; Other Names: Expanded Hemodialysis; Nipro Elisio HX; Sharp Cut-Off Dialyzer; Medium Cut-Off Dialyzer
Active Comparator: Conventional Hemodialysis; Participants will receive their regularly scheduled hemodialysis treatments using a high-flux dialyzer (as prescribed in routine care).	Device: High-Flux Dialyzer; A hemodialysis filter (known as a dialyzer) that is that is widely used across Canada for hemodialysis treatments.; Other Names: Conventional Hemodialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary 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.	From randomization to event (death) or end of treatment (average 2.9 years follow-up), whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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.	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.	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.	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.	From randomization to event (functioning kidney transplant) or end of treatment (average 2.9 years follow-up), whichever comes first.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Routine Care Symptoms	Routine care symptoms assessed using the Edmonton Symptoms Assessment System Revised Renal (ESAS-r: Renal) instrument, as recorded in usual care. Data will be abstracted from routine clinical records. The ESAS-r: Renal evaluates 12 symptoms on a 0-10 scale, with assessments every 3-6 months. The minimum value is 0, meaning no experience of specified symptom. The maximum value is 10 meaning, worst possible experience of specified symptom. This will be done only in units that routinely administer this instrument and participation in reporting this outcome is optional for sites.	From randomization to the end of treatment (average 2.9 year follow-up)
Healthcare-Associated Costs	The investigator will assess healthcare-associated costs in the subset of patients enrolled in Ontario using linked administrative databases with a standard method developed by the Institute for Clinical Evaluative Sciences (ICES).	From randomization to the end of treatment (average 2.9 year follow-up)
Neutrophil to Lymphocyte Ratio	The ratio between the neutrophil count and lymphocyte count derived from a complete blood count measurement performed in routine care and captured in the Ontario Laboratory Information System. This measures is typically collected every 4-6 weeks as part of standard dialysis care in Ontario.	From randomization to the end of treatment (average 2.9 year follow-up)
Blood Hemoglobin Concentration	Hemoglobin concentration from a complete blood count measurement performed in routine care and captured in the Ontario Laboratory Information System. This measures is typically collected every 4-6 weeks as part of standard dialysis care in Ontario.	From randomization to end of treatment (average 2.9 years follow-up)
Serum Albumin Concentration	Serum albumin concentration measured in routine care and captured in the Ontario Laboratory Information System. This measures is typically collected every 4-6 weeks as part of standard dialysis care in Ontario.	From randomization to the end of treatment (average 2.9 year follow-up)
Erythropoietin Stimulating Agent (ESA) Utilization	ESAs include darbepoetin or epoetin. Doses will be expressed as the dose per week. Dose will be converted to the weekly total epoetin dose and expressed as units per week. Subcutaneous and intravenous dosing will be considered equivalent. Data will be obtained from local medical record review and reported approximately every 6 months. Participation in reporting of this outcome is optional for sites and will only be assessed in a subset of participating sites.	From randomization to end of treatment (average 2.9 years follow-up)

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
• Collaborators: London Health Sciences Centre; ICES; Schulich School of Medicine and Dentistry; Statistics Canada; Nipro Canada Corporation
• Investigators: Principal Investigator: Pavel S Roshanov, MD MSc FRCPC, London Health Sciences Centre Research Institute; Study Chair: Amit X Garg, MD PhD FRCPC FACP, London Health Sciences Centre Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: RCT; Dialyzer; Expanded Hemodialysis; Hemodialysis Filter; Nipro Elisio HX; Super-High Flux Dialyzer; High-Flux Dialyzer
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency, Chronic
• Other Study ID Numbers: 4954; R-25-209 (Other Identifier: London Health Sciences Centre)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No