SODium BICarbonate for Metabolic Acidosis in the ICU

Shock Clinical Trial

— SODa-BIC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05697770
• Other study ID #: ANZIC-RC/ASN001
• Status: Recruiting
• Phase: Phase 3
• Start date: April 26, 2023
• Est. completion date: June 2027

Study information

• Verified date: June 2024
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: Mairead McNamara
• Phone: +613 9903 0513
• Email: mairead.mcnamara[@]monash.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

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 enrollment, whichever comes first.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 2027
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acidosis
• Metabolic Acidosis
• Shock

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Grapmians Health	Ballarat	Victoria
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Casey Hospital	Berwick	Victoria
Australia	Cairns Hospital	Cairns	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Queen Elizabeth II Jubilee Hospital	Coopers Plains	Queensland
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Footscray Hospital	Footscray	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	The Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Peninsula Private Hospital	Langwarrin	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Epworth	Richmond	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Royal Darwin Hospital	Tiwi	Northern Territory
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Australia	Princess Alexandra Hopsital	Woolloongabba	Queensland
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Wellington Regional Hospital	Wellington
Oman	Sultan Qaboos Comprehensive Cancer Care and Research Center	Seeb

Sponsors (1)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre

Countries where clinical trial is conducted

Australia,  New Zealand,  Oman, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Incidence and the maximum stage of AKI in the first 7 days after randomization	According to KDIGO criteria	7 days after randomization
Other	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)
Other	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)
Other	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)
Other	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)
Primary	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	30-day in-hospital mortality	All-cause in-hospital mortality at day 30	30 days or at hospital discharge (whichever occurs first)
Secondary	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)
Secondary	Persistent renal dysfunction	Defined as an elevation of the creatinine level to = 200% of baseline	30 days or at hospital discharge (whichever occurs first)
Secondary	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)
Secondary	ICU mortality	All-cause ICU mortality at day 30	30 days or at hospital discharge (whichever occurs first)
Secondary	Hospital mortality	All-cause hospital mortality at day 90	90 days or at hospital discharge (whichever occurs first)
Secondary	90-day in-hospital mortality	All-cause mortality at day 90	90 days or at hospital discharge (whichever occurs first)