Outcomes of a Higher vs. Lower Hemodialysate Magnesium Concentration (Dial-Mag)

Outcomes of a Higher vs. Lower Hemodialysate Magnesium Concentration: A Pragmatic Cluster-randomized Clinical Trial in Hemodialysis Centres

Many patients on hemodialysis have low levels of magnesium. Magnesium is needed to keep the heart, kidneys, and other organs working properly. Patients with low serum magnesium concentration have a higher risk of death, heart issues, muscle cramps and fractures. There are several reasons why patients on dialysis have low levels of magnesium-these include poor diet, medication interference, and the dialysis procedure itself, which leaches small amounts of magnesium from the blood during each treatment.

One way to make sure that patients on dialysis are getting enough magnesium is to increase its concentration in the dialysate. The investigator would like to do a randomized controlled trial to determine the effect of increasing the concentration of magnesium in the dialysate on the risk of people on dialysis dying or being admitted to the hospital due to heart issues. The investigator thinks increasing the magnesium in the dialysate will help patients live longer, have fewer hospitalisations related to heart disease and patients may also experience less cramping associated with dialysis.

This simple adjustment to the dialysis procedure can be done at little to no cost and may even reduce overall healthcare costs. If the investigator can show that increasing magnesium in the dialysate improves patients' health, then it could become the standard of care for dialysis centres.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Diseases; Hemodialysis; End-Stage Kidney Disease
• Intervention / Treatment: Other: Dialysate magnesium formulation of 1.5 mEq/L (0.75 mmol/L).; Other: Dialysate magnesium formulation of ≤1.0 mEq/L (≤0.5 mmol/L).

Detailed Description

1. Statement of the health problem or issue

   In end-stage kidney disease, dialysis is needed to remove toxins and electrolytes that would otherwise accumulate in a patient's blood. The fluid used in dialysis, the dialysate, contains magnesium, and the lower the concentration of dialysate magnesium, the more magnesium is removed from a patient's body during dialysis. Understanding the optimal amount of magnesium to include in the dialysate is crucial as magnesium regulates more than 300 enzymes in the body and is vital to heart, muscle, and bone health.

   In Canada, the dialysate is prepared by central suppliers and contains magnesium in concentrations of 0.38, 0.5, or 0.75 mmol/L. In the absence of clinical trial evidence, there is no consensus on what magnesium concentration is best, and all 3 concentrations are used today in Canadian hemodialysis centres.

2. Objective of the project

   In outpatients receiving conventional hemodialysis, to determine if providing a higher versus lower dialysate magnesium concentration (0.75 vs. ≤0.5 mmol/L) as a centre policy alters outcomes important to patients and their providers.

3. Outline

   This is a pragmatic, two-arm, parallel-group, cluster-randomized, open-label, multicentre, comparative-effectiveness trial embedded into routine care in hemodialysis centres in Canada. Centres have been randomized to, and are receiving a dialysate magnesium concentration of 0.75 mmol/L or ≤0.5 mmol/L in the intervention and control groups, respectively. Patients receiving maintenance hemodialysis at these centres will be followed for study outcomes during the trial follow-up period.

   The trial is highly pragmatic to facilitate high intervention adherence and extensive uptake of the findings; pragmatic features include (i) broad eligibility criteria, (ii) all eligible dialysis centres offering facility-based maitenance hemodialysis were recruited into the trial, (iii) participating centres are well representative of the variety of setting patients recieve care in, (iv) intervention implementation within routine clinical care delivered by dialysis unit personnel rather than researchers, (v) flexible intervention delivery and use of co-interventions, (vi) follow-up of patient outcomes using routinely collected data sources, (vii) an intention-to-treat analysis using all available data, and (viii) outcomes highly relevant to patients.

4. What is unique/innovative about the project?

   The investigator usually needs to study a large number of patients in a clinical trial to reliably understand the effects of a treatment. Normally, a study with 15,000 patients would cost more than $15 million dollars to conduct; however, this study will provide a reliable answer to the question being asked and cost less than $4 million. This is because the majority of data is already being collected by the healthcare system. For example, when a patient is hospitalized for a heart attack or stroke, this information is recorded in a secure healthcare database. The investigator will be able to analyze these healthcare data at the end of the study (and link patient outcomes to the type of dialysis treatment received (i.e. treatment or control). This innovative study design means that the study will be much larger (but cost much less) than a traditional clinical trial.

   This pragmatic trial includes all patients who receive facility-based maintenance hemodialysis in participating centres. High-risk patients with multiple comorbidities, including cognitive impairments or disabilities, who are often excluded from trials because of their high-risk status are eligible for participation in the Dialysate Magnesium trial. By including patients from a variety of medical, ethnic, geographic, and socioeconomic backgrounds, the results of the trial should be broadly generalizable.

5. What is the impact of the proposed research?

For patients with severe kidney failure (10,000 in Ontario and >2 million worldwide), hemodialysis provides a life-saving treatment option; however a tragic 20-40% of patients die within one year of starting hemodialysis. The dialysate is a critical component of hemodialysis, yet little evidence is available to guide its optimal formulation. Dialysate magnesium in particular has received little scientific attention until recently, with new research suggesting that a higher dialysate magnesium concentration may benefit patients. Outcomes that may be improved include mortality, cardiovascular outcomes, and muscle cramps.

While it is possible to raise the concentration of serum magnesium through oral supplements, using dialysis to do this is simpler and safer. It has little to no additional cost, does not add to a patient's pill burden, is not dependent on an adherent patient taking their pills, and avoids the gastrointestinal side effects of oral magnesium supplements.

If the investigator is able to demonstrate that a higher dialysate magnesium concentration improves patient outcomes, this formulation can be readily adopted to improve the care of ∼2 million patients receiving hemodialysis worldwide.

• Study Type: Interventional
• Enrollment (Estimated): 25000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • London Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion (Hemodialysis Center Level):

1. The hemodialysis center must be expected to treat at least 15 different individuals with facility-based maintenance hemodialysis over the trial period.
2. The hemodialysis center must use a system permitting the adoption of the randomly allocated dialysate Mg concentration (e.g., centers using BiCart® dialysate products, which do not include a dialysate Mg concentration of 0.75 mmol/L, were not eligible to participate).
3. The medical director, in consultation with local partners, must approve the randomization of their center and the adoption of the allocated dialysate Mg concentration as a center-wide policy for the trial period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Higher dialysate magnesium	Other: Dialysate magnesium formulation of 1.5 mEq/L (0.75 mmol/L).; (Dialysate magnesium concentration currently used in Canada and the United States)
Active Comparator: Lower dialysate magnesium	Other: Dialysate magnesium formulation of ≤1.0 mEq/L (≤0.5 mmol/L).; (Dialysate magnesium concentration currently used in Canada and the United States)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite of all-cause mortality or major cardiovascular-related hospitalizations	Data on all-cause mortality will be ascertained using provincial vital statistics databases. Major cardiovascular-related hospitalization (for myocardial infarction, ischemic stroke, or congestive heart failure) will be ascertained using most responsible diagnosis ICD-10 codes in the Canadian Institute for Health Information's Discharge Abstract Database.	Four Years
Self-reported muscle cramps	Self-reported muscle cramps. For self-reported muscle cramps patients will be able to voluntarily and anonymously answer a question on muscle cramps to describe on average how much this symptom bothered them in the past week. Responses will be recorded on a 11-point scale, with 0 indicating absence of the symptom and 10 indicating the symptom is at its worst. The question will be made available in the dialysis centre approximately twice a year. No patient identifiers will be collected, and this outcome will be assessed at the level of the centre. Data from the Spring 2026 collection period will be used in the primary analysis	Four years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	The all-cause mortality component of the primary composite outcome will be examined. Data on all-cause mortality will be ascertained using provincial vital statistics databases	Four Years
Major cardiovascular-related hospitalization	The major cardiovascular-related hospitalization component of the primary composite outcome will be examined. Major cardiovascular-related hospitalization (hospital admission for myocardial infarction, ischemic stroke, or congestive heart failure) will be ascertained using most responsible diagnosis ICD-10 codes in the Canadian Institute for Health Information's Discharge Abstract Database.	Four years

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
• Collaborators: Canadian Institutes of Health Research (CIHR); Alberta Health services; University of Calgary; Queen's University; The Ontario Spor Support Unit; Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease; ICES; The Ottawa Hospital Research Institute; Alberta Strategy for Patient Oriented Research Support Unit (AbSPORU); Strategy for Patient Orientated Research; Ontario Renal Network; Seven Oaks Hospital Chronic Disease Innovation Centre; Manitoba Centre for Health Policy; George & Fay Yee Centre for Health Care Innovation; BC Renal Agency
• Investigators: Principal Investigator: Amit X Garg, PhD, MD, ICES, Lawson, London Health Sciences Centre

Publications and helpful links

General Publications

• Dial-Mag Investigator Writing Committee*; Killin L, Bohm C, Harris C, MacRae JM, Shah N, Thompson S, Tonelli M, Luo B, Sontrop JM, Acedillo RR, Al-Jaishi AA, Anderson S, Antonsen J, Bagga A, Beaubien E, Berry D, Blake PG, Brown PA, Bueti J, Chan CT, Cote B, Cowan AC, Cuerden MS, Day NE, Dev V, Dhruve M, Djurdjev O, Gregor L, Hiremath S, Joseph G, Kammila S, Kiaii M, Kumar Kolusu E, Lacson E Jr, Mazurat A, Molnar AO, Nathoo B, Nistico A, Oliver MJ, Pandeya S, Parmar MS, Perkins D, Quinn K, Romann A, Sasal J, Shulman T, Silver SA, Singh A, Louis IS, Steele A, Tangri N, Ting RH, Vorster H, Wadehra DB, Wald R, Walters J, Whitlock RH, Yao S, Zacharias J, Garg AX. Outcomes of Adopting a Higher Versus Lower Concentration of Hemodialysate Magnesium as a Center-Wide Policy (Dial-Mag): A Clinical Research Protocol of a Pragmatic, Registry-Based, Cluster Randomized Trial. Can J Kidney Health Dis. 2025 Dec 9;12:20543581251385011. doi: 10.1177/20543581251385011. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2022
• Primary Completion (Actual): March 31, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Mortality; Dialysis; Kidney Disease; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Cardiovascular events; Cluster Randomized Controlled Trial; Dialysate Magnesium; Muscle cramps
• Additional Relevant MeSH Terms: Urogenital Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; 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; Signs and Symptoms; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Muscle Cramp; Pharmaceutical Solutions; Dialysis Solutions
• Other Study ID Numbers: R-13-999

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