High Versus Low Bicarbonate Bath in Critically-ill Patients Receiving Continuous Renal Replacement Therapy

High Versus Low Bicarbonate Bath in Critically-ill Patients Receiving Continuous Renal Replacement Therapy: a Pragmatic Randomized Control Trial

Researchers are trying to determine which dialysis solution, low bicarbonate fluid (22 mmol/L) or high bicarbonate fluid (32 mmol/L), is better in subjects with acute kidney injury (acute kidney failure) and metabolic acidosis that are admitted to the intensive care unit and require continuous renal replacement therapy (also known as continuous dialysis).

Study Overview

• Status: Withdrawn
• Conditions: Acute Kidney Injury; Acute Kidney Failure; Metabolic Acidosis
• Intervention / Treatment: Drug: Low bicarbonate solution (22 mmol/L); Drug: High Bicarbonate solution (32 mmol/L)

Detailed Description

This is a prospective randomized trial that will be conducted at Mayo Clinic in Rochester Minnesota. It will be based on Good Clinical Practice Standards and performed under IRB supervision. This will be a pragmatic clinical trial due to the nature of the intervention and short interval for making a clinical decision. While dialysis in general is valid in cases of severe AKI and metabolic acidosis, there remains uncertainty as to which replacement fluid to use. In one retrospective study, using high bicarbonate replacement fluid was associated with worse outcomes, even after accounting for several important confounders. While this intervention is valid in cases of severe metabolic acidosis (pH<7), there has not been much data to support the use of either intervention in cases of any metabolic acidosis in general.

While both interventions are equally valid, to our knowledge, there is no randomized clinical trial evaluating the difference of either intervention on outcomes. There is limited evidence in the literature on benefit or harm associated with either of the interventions on the outcomes thus generating a clinical equipoise. This pivotal study should help guide nephrologists and intensivists on the appropriate prescription of CRRT.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Adult patients (≥ 18 years of age)
• Ability to obtain informed consent, either from patient or legally authorized representative (LAR)
• Diagnosis of AKI according to KDIGO definition [an increase in serum creatinine concentration of greater than or equal to 0.3 mg/dL within the first 48 hours of injury, a relative increase in serum creatinine of greater than or equal to 50% (1.5-fold from baseline) within the first 7 days of injury, or a reduction in urine output (<0.5 mL/kg/h for more than 6 hours)]
• CRRT initiated for the first time during current ICU admission.
• Bicarbonate ≤ 22 mEq/L
• Arterial pH between 7.05 and 7.25(if an ABG is not available, venous pH must be between 7.00 and 7.20)

Exclusion Criteria

• Pregnancy (women of child-bearing potential must have a negative pregnancy test)
• Diagnosis of End-Stage renal disease and receiving Hemodialysis or peritoneal dialysis prior to ICU admission (this information will be easily obtained by the nephrology team)
• Arterial pH <7.05 or >7.25 (if an ABG is not available, Venous pH <7.00 or >7.20)
• Potassium level >6.0 mmol/L

• Severe acute liver failure meeting all the following criteria):

  • INR >2
  • AST/ALT more than 500 U/L and
  • Bilirubin more than 12 mg/dL)
• Previous enrollment in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Low bicarbonate arm (22 mmol/L); PHOXILLUM solutions are used as a replacement solution in Continuous Renal Replacement Therapy. The one to be used in this study has bicarbonate concentration of 22 mmol/L.	Drug: Low bicarbonate solution (22 mmol/L); Participants randomized to this arm will be started on CRRT using Phoxillum as the replacement fluid.; Other Names: Phoxillum
ACTIVE_COMPARATOR: High Bicarbonate (32 mmol/L); PrismaSATE is another replacement solution used in Continuous Renal Replacement Therapy. The one to be used in this study has bicarbonate concentration of 32 mmol/L.	Drug: High Bicarbonate solution (32 mmol/L); Participants randomized to this arm will be started on CRRT using Prismasate as the replacement fluid.; Other Names: Prismasate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital mortality	Discharge status: death	120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to achieve pH >7.3	The number of hours it took each participant to have an arterial pH of >7.3 or a venous pH > 7.35 following CRRT initiation	30 days
Major Adverse Kidney events	Composite outcome of death, persistent kidney dysfunction (creatinine more than 1.5 times baseline) or need for renal replacement therapy at specified time intervals.	120 Days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Kianoush B Kashani, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2019
• Primary Completion (ANTICIPATED): April 1, 2024
• Study Completion (ANTICIPATED): April 1, 2024

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 15, 2019
• First Posted (ACTUAL): February 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Acid-Base Imbalance; Renal Insufficiency; Acute Kidney Injury; Acidosis; Pharmaceutical Solutions
• Other Study ID Numbers: 18-010147

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: Yes
• Studies a U.S. FDA-regulated device product: No