ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12620001361998

Ethics application status

Approved

Date submitted

22/10/2020

Date registered

17/12/2020

Date last updated

30/10/2023

Date data sharing statement initially provided

17/12/2020

Date results information initially provided

24/10/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

SODium BICarbonate for metabolic acidosis in the Intensive Care Unit: A pilot, multicentre, randomized, double-blind clinical trial

Scientific title

SODium BICarbonate for metabolic acidosis in the Intensive Care Unit: A pilot, multicentre, randomized, double-blind clinical trial

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

SODa-BIC

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Metabolic acidosis

Condition category

Condition code

Metabolic and Endocrine

Other metabolic disorders

Emergency medicine

Other emergency care

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Sodium bicarbonate 8.4% (1000 mEq/L) will be diluted in a 5% dextrose (D5W) solution (500 milliliters bag). For the preparation, 300 mL of D5W will be removed and 300 mL of sodium bicarbonate 8.4% added to prepare the bicarbonate solution in total volume of 500 mL (final concentration: 600 mEq/L).

Allocated study drug will be continuously infused targeting a pH > 7.30 and a base excess (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.

The infusion will start at 100 mL/hr and be kept at this rate until both targets (pH and BE) are achieved. Then, once both targets are achieved it will be decreased to 25 mL/hr and kept constant at this infusion rate until 5 hours after the start of the infusion. After 5 hours of the start of the infusion, the infusion will be stopped independently of the results of the arterial blood gas analysis.

Arterial blood gases will be obtained in pre-defined moments within the first 5 hours (at 0, 1 [± 0.1 hours], 3 [± 0.5 hours], and 5 [± 1 hour] hours after the start of the infusion), and then at 12 (± 2 hours), 18 (± 2 hours) and 24 (± 2 hours) hours after the start of the drug infusion. The maximum time of infusion is up to 5 hours after the start of the infusion, until RRT start or ICU discharge, whichever comes first. Open-label sodium bicarbonate infusion is allowed if clinically indicated.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Continuous infusion of 5% dextrose (D5W) and usual care according to local protocol (as per hospital protocol). All strategy and arterial blood gas sampling will follow the same approach as in the sodium bicarbonate group.

Control group

Active

Outcomes

Primary outcome [1]

Number of hours alive and free of vasopressors at day 7 (168 hours) after randomization. This is defined as the time, censored at 7 days, that a patient was both alive and had not received vasopressors for at least 12 hours. If a patient died while receiving vasopressor therapy following the index episode, the patient is assigned zero hours for this outcome. If a patient was weaned from all vasopressors for 12 consecutive hours, then all of the remaining time through day 7 was treated as success, even if the patient died or had vasopressors restarted after weaning within the 7-day period. The outcome will be assess through patient medical records.

Timepoint [1]

7 days (168 hours) after randomization

Secondary outcome [1]

Time to correction of BE (through patient medical records)

Timepoint [1]

6 hours after the start of the infusion

Secondary outcome [2]

Time to correction of pH (through patient medical records)

Timepoint [2]

6 hours after the start of the infusion

Secondary outcome [3]

Recurrence of moderate metabolic acidosis (according to the inclusion criteria used in the study) in the first 7 days after randomization (through patient medical records)

Timepoint [3]

7 days after randomization

Secondary outcome [4]

Mean bicarbonate levels in the first 24 hours of infusion (through blood samples collected and registered in the patient medical records)

Timepoint [4]

24 hours after the start of the infusion

Secondary outcome [5]

Incidence and the maximum stage of acute kidney injury (according to KDIGO criteria) in the first 7 days after randomization (through patient medical records)

Timepoint [5]

7 days after randomization

Secondary outcome [6]

Receipt of renal replacement therapy in the first 28 days (through patient medical records)

Timepoint [6]

28 days after randomization

Secondary outcome [7]

Delta of Sequential Organ Failure Assessment (SOFA) score at 72 hours - defined as the initial total SOFA* score minus the day three (72 hours) SOFA score
*total SOFA = Sequential Organ Failure Assessment = sum of each organ system point score. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The organ scores are ranging from 0-4, with the best score being 0 and the worst being 4 points. The maximal (and worst) total SOFA score is 24 points.

Timepoint [7]

72 hours after randomization

Secondary outcome [8]

ICU length of stay (through patient medical records)

Timepoint [8]

90 days after randomization

Secondary outcome [9]

Hospital length of stay (through patient medical records)

Timepoint [9]

90 days after randomization

Secondary outcome [10]

ICU mortality

Timepoint [10]

90 days after randomization

Secondary outcome [11]

Hospital mortality

Timepoint [11]

90 days after randomization

Secondary outcome [12]

28-day mortality

Timepoint [12]

28 days after randomization

Secondary outcome [13]

90-day mortality

Timepoint [13]

90 days after randomization

Secondary outcome [14]

28 day cumulative vasopressor free hours (through patient medical records)

Timepoint [14]

28 days after randomization

Secondary outcome [15]

28 day renal replacement therapy–free days (through patient medical records)

Timepoint [15]

28 days after randomization

Secondary outcome [16]

Hypokalaemia needing correction (defined as potassium level < 3.5 mEq/L needing correction, and assessed through patient medical records)

Timepoint [16]

During infusion

Secondary outcome [17]

Hypocalcaemia needing correction (defined as ionized calcium level < 1.15 mmol/L needing correction, and assessed through patient medical records)

Timepoint [17]

During infusion

Secondary outcome [18]

Dysnatraemia (Na > 155 mEq/L) (through patient medical records)

Timepoint [18]

During infusion

Secondary outcome [19]

Strong in difference (SID) in the first 24 hours after the start of the infusion (through patient medical records)

Timepoint [19]

24 hours after the start of the infusion

Secondary outcome [20]

pH in the first 24 hours after the start of the infusion (through blood samples collected and registered in the patient medical records)

Timepoint [20]

24 hours after the start of the infusion

Secondary outcome [21]

BE in the first 24 hours after the start of the infusion (through blood samples collected and registered in the patient medical records)

Timepoint [21]

24 hours after the start of the infusion

Secondary outcome [22]

PaCO2 in the first 24 hours after the start of the infusion (through blood samples collected and registered in the patient medical records)

Timepoint [22]

24 hours after the start of the infusion

Secondary outcome [23]

Strong ion gap (SIG) in the first 24 hours after the start of the infusion (through patient medical records)

Timepoint [23]

24 hours after the start of the infusion

Eligibility

Key inclusion criteria

The target population is vasopressor-dependent, adult critically ill patients, with moderate metabolic acidosis.

All the diagnostic criteria of moderate metabolic acidosis below have to be fulfilled within the last 2 hours before randomization, and a vasopressor is being infused continuously at the time of randomization.

1. Adult patients (>= 18 years);
2. Patient is within 48 hours of admission to the ICU;
3. Patient is receiving a continuous infusion of a vasopressor drug to maintain mean arterial pressure > 65 mmHg;
4. A dedicated line (central or peripheric) is available (or is about to be made available within 1 hour after randomization); and
5. Patient has at least a moderate metabolic acidosis, defined as:
a. pH < 7.30; and
b. BE < -4 mEq/L; and
c. PaCO2 < 45 mmHg.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Proven digestive or urinary tract loss of sodium bicarbonate (e.g., acute diarrhoea, ileostomy, or drainage of pancreatic or biliary duct); or
2. DKA; or
3. Stage IV or V chronic kidney disease; or
4. Using renal replacement therapy (acute or chronic); or
5. Received sodium bicarbonate within 24 hours of screening; or
6. Dysnatraemia (serum Na greater than or equal to 155 mEq/L or < 120 mEq/L); or
7. Hypokalaemia (serum K < 2.5 mEq/L); or
8. Pulmonary oedema with PaO2 / FiO2 < 100; or
9. Hypocalcaemia (iCa < 0.8mmol/L); or
10. Known or suspected poisoning of antidepressant or antipsychotic poisoning agents that may cause high anion gap acidosis (methanol, PEG, aspirin); or
11. Suspected intoxication with unknown aetiology; or
12. Pregnancy or breastfeeding; or
13. Limitation of medical therapy orders (DNR, DNI); or
14. Imminent or inevitable death; or
15. In the opinion of the treating clinical team the patients will almost certainly receive RRT in the next 6 hours; or
16. Traumatic brain injury (or substantial risk for intracranial hypertension); or
17. Clinician believes that being enrolled in intervention or control arm is not in the best interest of the patient; or
18. Previous enrolment in this study ever.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Central randomization in the internet

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomization with blocks of random sizes and using an allocation list created by computer software and by an independent investigator

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Data analysis will be performed on an intention-to-treat basis. Summary statistics will be used to describe the clinical data and presented as mean ± SD, median with interquartile range or percentages as appropriate. Chi-squared analysis with Fisher’s exact test (when appropriate), and Student’s t-test (Mann Whitney U test for non-normal distributions) will be used to compare data between the active treatment group and the control group with statistical significance declared for probability values of less than 0.05. A full statistical analysis plan will be prepared before the final of the recruitment.

Recruitment

Recruitment status

Stopped early

Data analysis

Data analysis is complete

Reason for early stopping/withdrawal

Participant recruitment difficulties

Date of first participant enrolment

Anticipated

1/04/2021

Actual

2/06/2021

Date of last participant enrolment

Anticipated

30/04/2022

Actual

12/08/2022

Date of last data collection

Anticipated

31/12/2022

Actual

4/11/2022

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

The Alfred - Melbourne

Recruitment hospital [3]

Western Hospital - Footscray - Footscray

Recruitment hospital [4]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [5]

Sunshine Hospital - St Albans

Recruitment hospital [6]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [7]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [8]

The Northern Hospital - Epping

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3004 - Melbourne

Recruitment postcode(s) [3]

3052 - Parkville

Recruitment postcode(s) [4]

3011 - Footscray

Recruitment postcode(s) [5]

3021 - St Albans

Recruitment postcode(s) [6]

3220 - Geelong

Recruitment postcode(s) [7]

3168 - Clayton

Recruitment postcode(s) [8]

3076 - Epping

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Wellington

Country [2]

Japan

State/province [2]

Tokyo

Country [3]

Brazil

State/province [3]

São Paulo

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Australian and New Zealand Intensive Care Research Centre

Address [1]

Level 3
553 St Kilda Road
Melbourne
VIC 3004
Australia

Country [1]

Australia

Primary sponsor type

Other

Name

Australian and New Zealand Intensive Care Research Centre

Address

Level 3
553 St Kilda Road
Melbourne
VIC 3004
Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Health Ethics Committee

Ethics committee address [1]

55 Commercial Rd,
Melbourne
VIC 3004
Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/11/2020

Approval date [1]

31/03/2021

Ethics approval number [1]

HREC/70181/Alfred-2020

Summary

Brief summary

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.

The trial aims to assess if the infusion of sodium bicarbonate in vasopressor-dependent patients with moderate metabolic acidosis admitted to the ICU increases the number of vasopressor-free hours at day 7.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Andrew Udy

Address

Alfred Health
55 Commercial Road
Melbourne VIC 3004
PO Box 315 Prahran
VIC 3181 Australia

Country

Australia

Phone

+61 0 438 755 568

Fax

[email protected]

Contact person for public queries

Name

Dr Ary Serpa Neto

Address

Australian and New Zealand Intensive Care-Research Centre (ANZIC-RC)
Monash University
Level 3,
553 St Kilda Road
Melbourne,
VIC 3004

Country

Australia

Phone

+61 0 432 749 435

Fax

[email protected]

Contact person for scientific queries

Name

Dr Ary Serpa Neto

Address

Australian and New Zealand Intensive Care-Research Centre (ANZIC-RC)
Monash University
Level 3,
553 St Kilda Road
Melbourne,
VIC 3004

Country

Australia

Phone

+61 0 432 749 435

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All individual de-identified data collected during the study

When will data be available (start and end dates)?

After the publication of the first paper of the collaboration and available for 5 years after publication

Available to whom?

Scientific investigators interested in the field

Available for what types of analyses?

Secondary analyses defined in discussion with the Steering Committee of the study

How or where can data be obtained?

After contact with the principal investigator and study coordinator ([email protected])

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	Citations or Other Details	Attachment
Study results article	Yes	Serpa Neto A, Fujii T, McNamara M, Moore J, Young ... [More Details]
Basic results	No		380795-(Uploaded-23-08-2023-10-32-06)-Basic results summary.pdf
Plain language summary	No	In patients with metabolic acidosis (acid blood) t... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.	2023	https://dx.doi.org/10.1097/CCM.0000000000005955

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically