SODium BICarbonate for Metabolic Acidosis in the ICU

NCT ID: NCT05697770

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-26
• Study Completion Date: 2026-07-31

Brief Summary

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.

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.

Conditions

Metabolic Acidosis; Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Sodium bicarbonate

Intervention Type: DRUG

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.

5% dextrose

Standard 500 mL bag of D5W.

Group Type: ACTIVE_COMPARATOR

5% Dextrose

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Australian and New Zealand Intensive Care Research Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ary Serpa Neto, PhD

Role: PRINCIPAL_INVESTIGATOR

ANZIC RC, Monash university

Locations

Canberra Hospital

Garran, Australian Capital Territory, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Sutherland Hospital

Caringbah, New South Wales, Australia

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Orange Health Service

Orange, New South Wales, Australia

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Royal Darwin Hospital

Tiwi, Northern Territory, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Cairns Hospital

Cairns, Queensland, Australia

Queen Elizabeth II Jubilee Hospital

Coopers Plains, Queensland, Australia

Townsville University Hospital

Douglas, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Ipswich Hospital

Ipswich, Queensland, Australia

Mater Hospital

South Brisbane, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Princess Alexandra Hopsital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Grapmians Health

Ballarat, Victoria, Australia

Bendigo Hospital

Bendigo, Victoria, Australia

Casey Hospital

Berwick, Victoria, Australia

The Victorian Heart Hospital

Clayton, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Dandenong Hospital

Dandenong, Victoria, Australia

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Footscray Hospital

Footscray, Victoria, Australia

Frankston Hospital

Frankston, Victoria, Australia

University Hospital Geelong

Geelong, Victoria, Australia

The Austin Hospital

Heidelberg, Victoria, Australia

Peninsula Private Hospital

Langwarrin, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Epworth

Richmond, Victoria, Australia

Sunshine Hospital

St Albans, Victoria, Australia

Bunbury Regional Hospital

Bunbury, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Centro de Estudos e de Pesquisas em Terapia Intensiva

Curitiba, Paraná, Brazil

Jawaharlal Institute of Postgraduate Medical Education and Research

Puducherry, Puducherry, India

Deep Hospital

Ludhiana, Punjab, India

The Jikei University Hospital

Minato, Tokyo, Japan

Auckland City Hospital (CVICU)

Auckland, Auckland, New Zealand

Auckland City Hospital (DCCM)

Auckland, Auckland, New Zealand

Middlemore Hospital

Auckland, Auckland, New Zealand

Christchurch Hospital

Christchurch, Christchurch, New Zealand

Dunedin Hospital

Dunedin, Dunedin, New Zealand

Waikato Hospital

Hamilton, Hamilton, New Zealand

Wellington Regional Hospital

Wellington, , New Zealand

Sultan Qaboos Comprehensive Cancer Care and Research Center

Seeb, , Oman

King Abdullah International Medical Research Center

Riyadh, Riyadh Region, Saudi Arabia

Countries

Australia; Brazil; India; Japan; New Zealand; Oman; Saudi Arabia

References

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.

Reference Type: DERIVED

PMID: 40487345 (View on PubMed)

Other Identifiers

ANZIC-RC/ASN001

Identifier Type: -

Identifier Source: org_study_id