Dial-Bicarb Trial: Effects of a Lower vs. Higher Concentration of Dialysate Bicarbonate

Dial-Bicarb Trial: Effects of a Lower vs. Higher Concentration of Dialysate Bicarbonate for People Receiving Maintenance Hemodialysis

This is a pragmatic, two-arm, parallel-group, open-label, individual-randomized, superiority trial that will be conducted in hemodialysis units across Ontario. Patients at each dialysis unit will be randomly allocated into one of two study arms in a 1:1 ratio to receive a dialysate bicarbonate concentration of either 32 or 38 mmol/L. The intervention will be embedded into routine care and delivered by hemodialysis unit personnel.

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Failure; Hemodialysis
• Intervention / Treatment: Other: Bicarbonate

Detailed Description

Background: Bicarbonate is added to hemodialysis fluids to correct the metabolic acidosis that arises from kidney failure. Some dialysis centres in Canada add bicarbonate to a level of 32 mmol/L, while other centres add bicarbonate to a level of 38 mmol/L. It is unknown whether one level is better for people's health.

Objective: In patients receiving maintenance hemodialysis, to determine if providing a lower versus higher concentration of dialysate bicarbonate (32 versus 38 mmol/L) alters the risk of outcomes important to patients and their care providers.

Design, Setting, and Participants: This is a pragmatic, two-arm, parallel-group, open-label, individual-randomized, superiority trial that will be conducted in hemodialysis centres across Ontario. Patients at each dialysis centre will be randomly allocated into one of two study arms in a 1:1 ratio to receive a dialysate bicarbonate concentration of either 32 or 38 mmol/L. The intervention will be embedded into routine care and delivered by hemodialysis centre personnel. The concentration of dialysate bicarbonate is altered for a hemodialysis session through a simple setting on the machine.

Altered approach to patient consent: The study team, which includes patient partners, proposes an opt-out altered approach to patient consent to receive the trial-assigned concentration of dialysate bicarbonate. This is under a framework that Dial-Bicarb fits the required parameters to do so, as constructed in Canada's Tri-Council Policy Statement-2 (TCPS-2) Article 3.7A.

Primary Outcome: Two primary outcomes, all-cause mortality and recurrent all-cause non-elective hospitalizations.

Secondary Outcomes: Cardiovascular-related hospitalizations, infection-related hospitalizations, and fractures.

Data Collection: This trial will obtain information on patient characteristics and outcomes from provincial healthcare administrative databases, which are already collected as part of routine healthcare.

Planned Analysis: Treatment effects will be reported as hazard ratios accounting for the number of events and total follow-up time within arms.

Potential Impact: If a lower concentration of dialysate bicarbonate is shown to be superior, it could be easily adopted as the standard of care by hemodialysis centres globally at little added cost. This change in practice could help reduce premature deaths and hospitalizations among the more than 2 million people on hemodialysis worldwide.

• Study Type: Interventional
• Enrollment (Estimated): 14000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amber Molnar, MD; Phone Number: 33787 (905) 522-1155; Email: amolnar@stjosham.on.ca
• Study Contact Backup: Name: Amit Garg, MD; Phone Number: 519-685-8502; Email: Amit.Garg@lhsc.on.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The dialysis centre director and all nephrologists who provide care in the centre agree to trial participation.
• Adult patients 18 years of age and older, with a health card number, enter the trial after they receive hemodialysis for at least 90 days (about 3 months) so that patients with acute kidney injury who recover kidney function are excluded.

Exclusion Criteria:

- Participating centres are instructed that patients on in-centre nocturnal hemodialysis or in-centre frequent (greater than four times weekly) hemodialysis are not in the trial (and do not receive the allocated intervention), since these patients usually receive dialysate bicarbonate concentrations ≤32mmol/L as standard care (based on Ontario registry data, these modalities represent <5% of the hemodialysis patient population).

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
Active Comparator: Lower dialysate bicarbonate concentration (32 versus mmol/L); Patients at each dialysis unit will be randomly allocated into one of two study arms in a 1:1 ratio to receive a dialysate bicarbonate concentration of 32 mmol/L.	Other: Bicarbonate; Bicarbonate is added to hemodialysis fluids to correct the metabolic acidosis that arises from kidney failure. Some dialysis units in Canada add bicarbonate to a level of 32 mmol/L, while other units add bicarbonate to a level of 38 mmol/L. It is unknown whether one level is better for people's health.
Active Comparator: Higher dialysate bicarbonate concentration (38 mmol/L); Patients at each dialysis unit will be randomly allocated into one of two study arms in a 1:1 ratio to receive a dialysate bicarbonate concentration of 38 mmol/L.	Other: Bicarbonate; Bicarbonate is added to hemodialysis fluids to correct the metabolic acidosis that arises from kidney failure. Some dialysis units in Canada add bicarbonate to a level of 32 mmol/L, while other units add bicarbonate to a level of 38 mmol/L. It is unknown whether one level is better for people's health.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-elective hospitalizations	All-cause recurrent non-elective hospitalizations	Duration of the study, 4 years.
Mortality	All-cause mortality	Duration of the study, 4 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalizations and fractures	Cardiovascular-related hospitalizations, infection-related hospitalizations, and fractures.	Duration of the study, 4 years.

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR); ACT
• Investigators: Principal Investigator: Amit Garg, MD, LHSC

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: renal failure; kidney; pragmatic trial; bicarbonate; maintenance hemodialysis
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: 14410

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