SODium BICarbonate for Metabolic Acidosis in the ICU (SODa-BIC)

SODium BICarbonate for Metabolic Acidosis in the Intensive Care Unit (SODa-BIC): A Multicentre, Randomised, Double-blind Clinical Trial

This trial aims to assess if, among adults in the ICU with metabolic acidosis, an infusion of sodium bicarbonate diluted in 5% dextrose, compared with an infusion of 5% dextrose, reduces Major Adverse Kidney Events within 30 days of randomization.

Study Overview

• Status: Active, not recruiting
• Conditions: Shock; Metabolic Acidosis
• Intervention / Treatment: Drug: Sodium bicarbonate; Drug: 5% Dextrose

Detailed Description

Background: Metabolic acidosis refers to any process that elevates the concentration of hydrogen ions in the body, and is commonly encountered in critical illness. Lactic acidosis, diabetic ketoacidosis, and hyperchloremic acidosis are major examples seen in the intensive care unit (ICU). Metabolic acidosis may impair cardiac function, and sodium bicarbonate can be used to normalise blood pH. Despite being in common clinical usage, the clinical efficacy of sodium bicarbonate is still uncertain. Previous studies exploring the effects of sodium bicarbonate therapy have been limited and of variable quality.

Aim: This trial aims to assess if, among adults in the ICU with metabolic acidosis, an infusion of sodium bicarbonate diluted in 5% dextrose, compared with an infusion of 5% dextrose, reduces Major Adverse Kidney Events within 30 days of randomization.

Study Design: Phase 3, international, multicentre, double-blind, randomised clinical trial.

Participants: Adult patients (≥ 18 years old), admitted to the ICU within 48 hours, receiving a continuous infusion of a vasopressor drug to maintain a mean arterial pressure > 65 mmHg (or a mean arterial pressure target set by the treating clinician), a dedicated line (central or peripheral) is available (or is about to be made available within 1 hour after randomisation), and within two hours prior to randomisation the participant has metabolic acidosis, defined as: 1) pH < 7.30; 2) BE ≤ -4 mEq/L; and 3) PaCO2 ≤ 45 mmHg for non-intubated patients or PaCO2 ≤ 50 mmHg for non-intubated patients

Intervention: Patients will be randomly allocated in a 1:1 ratio to receive two treatments that are commonly used either an infusion of 5% dextrose (D5W) + sodium bicarbonate, or D5W alone, as a comparator. Study drug will be continuously infused targeting a pH 7.30 - 7.35 and a BE ≥ 0 mEq/L. The infusion will be maintained until this target is achieved and continued by titration thereafter for a maximum of 5 hours (to maintain target pH and base excess levels). All other aspects of care will be determined by the treating clinical team, including the use of additional fluid therapy, vasopressors, and other organ support modalities. Open-label sodium bicarbonate bolus infusion is allowed in both groups if clinically indicated.

Primary outcome: The primary outcome is the proportion of patients who meet one or more criteria for a major adverse kidney event within 30 days (MAKE 30). MAKE 30 is a composite of death, new receipt of renal-replacement therapy, or persistent renal dysfunction (defined as a final inpatient creatinine value ≥ 200% of the baseline value). All components of MAKE30 will be censored at hospital discharge or 30 days after enrolment, whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Caringbah, New South Wales, Australia, 2229
      • Sutherland Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Gosford, New South Wales, Australia, 2250
      • Gosford Hospital
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Orange, New South Wales, Australia, 2800
      • Orange Health Service
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Wahroonga, New South Wales, Australia, 2076
      • Sydney Adventist Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Northern Territory
    • Tiwi, Northern Territory, Australia, 0810
      • Royal Darwin Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
    • Coopers Plains, Queensland, Australia, 4108
      • Queen Elizabeth II Jubilee Hospital
    • Douglas, Queensland, Australia, 4814
      • Townsville University Hospital
    • Herston, Queensland, Australia, 4006
      • Royal Brisbane and Women's Hospital
    • Ipswich, Queensland, Australia, 4305
      • Ipswich Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hopsital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia
      • Flinders Medical Centre
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Grapmians Health
    • Bendigo, Victoria, Australia, 3550
      • Bendigo Hospital
    • Berwick, Victoria, Australia, 3806
      • Casey Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Clayton, Victoria, Australia, 3065
      • The Victorian Heart Hospital
    • Dandenong, Victoria, Australia, 3175
      • Dandenong Hospital
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital Melbourne
    • Footscray, Victoria, Australia, 3011
      • Footscray Hospital
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital
    • Geelong, Victoria, Australia, 3220
      • University Hospital Geelong
    • Heidelberg, Victoria, Australia, 3084
      • The Austin Hospital
    • Langwarrin, Victoria, Australia, 3910
      • Peninsula Private Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Richmond, Victoria, Australia, 3121
      • Epworth
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
  • Western Australia
    • Bunbury, Western Australia, Australia, 6230
      • Bunbury Regional Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 82530-200
      • Centro de Estudos e de Pesquisas em Terapia Intensiva
• India
  • Puducherry
    • Puducherry, Puducherry, India, 605006
      • Jawaharlal Institute Of Postgraduate Medical Education And Research
  • Punjab
    • Ludhiana, Punjab, India, 141002
      • Deep Hospital
• Japan
  • Tokyo
    • Minato, Tokyo, Japan, 105-0003
      • The Jikei University Hospital
• New Zealand
  • Wellington, New Zealand
    • Wellington Regional Hospital
  • Auckland
    • Auckland, Auckland, New Zealand, 1023
      • Auckland City Hospital (CVICU)
    • Auckland, Auckland, New Zealand, 1023
      • Auckland City Hospital (DCCM)
    • Auckland, Auckland, New Zealand, 2025
      • Middlemore Hospital
  • Christchurch
    • Christchurch, Christchurch, New Zealand, 4710
      • Christchurch Hospital
  • Dunedin
    • Dunedin, Dunedin, New Zealand, 9016
      • Dunedin Hospital
  • Hamilton
    • Hamilton, Hamilton, New Zealand, 3204
      • Waikato Hospital
  • Rotorua
    • Rotorua, Rotorua, New Zealand, 3010
      • Rotorua Hospital
• Oman
  • Seeb, Oman
    • Sultan Qaboos Comprehensive Cancer Care and Research Center
• Saudi Arabia
  • Riyadh Region
    • Riyadh, Riyadh Region, Saudi Arabia, 11481
      • King Abdullah International Medical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

All the diagnostic criteria of metabolic acidosis below have to be fulfilled within the last 2 hours before randomisation (pH, PaCO2 and BE from the same blood gas), and a vasopressor is being infused continuously at the time of randomization.

1. Adults (≥ 18 years);
2. Receiving a continuous infusion of a vasopressor to maintain mean arterial pressure > 65 mmHg (or a mean arterial pressure target set by the treating clinician);
3. A dedicated intravenous line (central or peripheral) is available (or insertion of such a line is planned within the next hour); and

4. Metabolic acidosis, defined as:

   1. pH < 7.30; and
   2. BE ≤ -4 mEq/L; and
   3. PaCO2 ≤ 45 mmHg for non-intubated patients or PaCO2 ≤ 50 mmHg for intubated patients.

Exclusion Criteria:

1. Fulfilled all eligibility criteria greater than 48 hours ago; or
2. Suspected clinically significant digestive or urinary tract loss of sodium bicarbonate (e.g., diarrhoea, ileostomy losses, renal tubular acidosis, or drainage of pancreatic or bile duct); or
3. DKA; or
4. Estimated glomerular filtration rate (eGFR) < 30 mL/min due to chronic kidney disease; or
5. Currently receiving sodium bicarbonate at the moment of randomisation (doses of sodium bicarbonate prior to randomisation are allowed); or
6. Currently receiving RRT (acute or chronic) or planned to start RRT in the next 3 hours (according to the treating clinical team); or
7. Severe dysnatraemia (serum Na ≥ 155 mEq/L or < 120 mEq/L); or
8. Hypokalaemia (serum K < 2.5 mEq/L); or
9. Pulmonary oedema with PaO2 / FiO2 < 100; or
10. Hypocalcaemia (iCa < 0.8mmol/L); or
11. Patients admitted to the ICU after a drug overdose or intoxication (including alcohol intoxication); or
12. Pregnancy or breastfeeding; or
13. Death is deemed to be inevitable as a result of the current acute illness and either the treating clinician, the patient or the substitute decision maker are not committed to full active treatment; or
14. Patients with a life expectancy < 30 days due to a chronic or underlying medical condition; or
15. Considered to be at high risk of cerebral oedema by the treating clinician (e.g. traumatic brain injury or acute brain disease); or
16. Clinician believes that being enrolled in intervention or control arm is not in the best interest of the patient; or
17. Previous enrolment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium bicarbonate; Sodium bicarbonate 8.4% (1000 mEq/L) will be diluted in a D5W solution (500 mL bag). For preparation, 300 mL of D5W will be removed and 300 mL of sodium bicarbonate 8.4% added to prepare the bicarbonate solution in a total volume of 500 mL (final concentration: 600 mEq/L).	Drug: Sodium bicarbonate; Sodium bicarbonate 8.4% will be continuously infused for a maximum of 5 hours. The infusion will start at 100 mL/hr and be kept at this rate until both pH and BE targets are achieved, following which, the infusion rate will be decreased to 25 mL/hr and kept constant at this rate until 5 hours has elapsed since the start of the infusion. At this point, the infusion will be stopped, independently, of the results of arterial blood gas analysis.
Active Comparator: 5% dextrose; Standard 500 mL bag of D5W.	Drug: 5% Dextrose; 5% dextrose will be continuously infused for a maximum of 5 hours. The infusion will start at 100 mL/hr and be kept at this rate until both pH and BE targets are achieved, following which, the infusion rate will be decreased to 25 mL/hr and kept constant at this rate until 5 hours has elapsed since the start of the infusion. At this point, the infusion will be stopped, independently, of the results of arterial blood gas analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAKE30 score	The primary outcome is MAKE30 from the date of randomisation. MAKE30 is defined as a composite of death from any cause, receipt of RRT, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline), all censored at hospital discharge or 30 days, whichever occurs first.	30 days or at hospital discharge (whichever occurs first)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day in-hospital mortality	All-cause in-hospital mortality at day 30	30 days or at hospital discharge (whichever occurs first)
Receipt of renal replacement therapy in the first 30 days	Receipt of renal replacement therapy in the first 30 days	30 days or at hospital discharge (whichever occurs first)
Persistent renal dysfunction	Defined as an elevation of the creatinine level to ≥ 200% of baseline	30 days or at hospital discharge (whichever occurs first)
Renal replacement therapy dependence at day 30	Defined by the receipt of any form of renal replacement therapy within ± 10 days of the 30-day time point following randomisation	30 days or at hospital discharge (whichever occurs first)
ICU mortality	All-cause ICU mortality at day 30	30 days or at hospital discharge (whichever occurs first)
Hospital mortality	All-cause hospital mortality at day 90	90 days or at hospital discharge (whichever occurs first)
90-day in-hospital mortality	All-cause mortality at day 90	90 days or at hospital discharge (whichever occurs first)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of metabolic acidosis in the first 7 days after randomization	Defined as pH < 7.30, BE ≤ -4 mEq/L and PaCO2 ≤ 45 mmHg	7 days after randomization
Incidence and the maximum stage of AKI in the first 7 days after randomization	According to KDIGO criteria	7 days after randomization
Vasopressor-free days at day 30	Defined as 30 - days receiving a continuous infusion of vasopressor [at any time and for any duration]; non-survivors at day 30 will receive 0	30 days or at hospital discharge (whichever occurs first)
Renal replacement therapy-free days at day 30	Defined as 30 - days receiving RRT; non-survivors at day 30 will receive 0	30 days or at hospital discharge (whichever occurs first)
ICU-free days at day 30	Defined as 30 - ICU length of stay; non-survivors at day 30 will receive 0	30 days or at hospital discharge (whichever occurs first)
Hospital-free days at day 90	Defined as 90 -hospital length of stay; non-survivors at day 90 will receive 0	90 days or at hospital discharge (whichever occurs first)
Health-Related Quality of Life	EQ-5D-5L	180 days

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Investigators: Principal Investigator: Ary Serpa Neto, PhD, ANZIC RC, Monash university

Publications and helpful links

General Publications

• Serpa Neto A, McNamara M, Cooper J, Fujii T, Higgins A, Hodgson C, Navarra L, Nichol A, Peake S, Rea-Neto A, Secombe P, See E, Taylor P, Young M, Zampieri FG, Young P, Bellomo R, Udy A; SODa-BIC investigators. Protocol summary and statistical analysis plan for the sodium bicarbonate for metabolic acidosis in the intensive care unit (SODa-BIC) trial. Crit Care Resusc. 2025 May 15;27(2):100108. doi: 10.1016/j.ccrj.2025.100108. eCollection 2025 Jun.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Actual): January 8, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: January 15, 2023
• First Submitted That Met QC Criteria: January 15, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Shock; Clinical trial; Metabolic acidosis; Sodium bicarbonate
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Acid-Base Imbalance; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Shock; Acidosis; Carbohydrates; Inorganic Chemicals; Sugars; Sodium Compounds; Hexoses; Monosaccharides; Carbon Compounds, Inorganic; Carbonates; Carbonic Acid; Bicarbonates; Glucose; Sodium Bicarbonate
• Other Study ID Numbers: ANZIC-RC/ASN001

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