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Trial registered on ANZCTR


Registration number
ACTRN12620001361998p
Ethics application status
Submitted, not yet approved
Date submitted
22/10/2020
Date registered
17/12/2020
Date last updated
17/12/2020
Date data sharing statement initially provided
17/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
SODium BICarbonate for metabolic acidosis in the Intensive Care Unit: A pilot, multicentre, double-blind, placebo controlled randomized clinical trial
Scientific title
SODium BICarbonate for metabolic acidosis in the Intensive Care Unit: A pilot, multicentre, double-blind, placebo controlled randomized clinical trial
Secondary ID [1] 302601 0
Nil known
Universal Trial Number (UTN)
Trial acronym
SODa-BIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic acidosis 319483 0
Condition category
Condition code
Metabolic and Endocrine 317448 317448 0 0
Other metabolic disorders
Emergency medicine 317449 317449 0 0
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, 3 [± 0.5 hours], and 5 [± 1 hour] hours after the start of the infusion), and then at 12, 18 and 24 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] 318883 0
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
Placebo

Outcomes
Primary outcome [1] 325483 0
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 6 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 6 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] 325483 0
7 days (168 hours) after randomization
Secondary outcome [1] 388092 0
Time to correction of BE (through patient medical records)
Timepoint [1] 388092 0
6 hours after the start of the infusion
Secondary outcome [2] 388093 0
Time to correction of pH (through patient medical records)
Timepoint [2] 388093 0
6 hours after the start of the infusion
Secondary outcome [3] 388094 0
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] 388094 0
7 days after randomization
Secondary outcome [4] 388095 0
Mean bicarbonate levels in the first 24 hours of infusion (through blood samples collected and registered in the patient medical records)
Timepoint [4] 388095 0
24 hours after the start of the infusion
Secondary outcome [5] 388096 0
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] 388096 0
7 days after randomization
Secondary outcome [6] 388097 0
Need of renal replacement therapy in the first 28 days (through patient medical records)
Timepoint [6] 388097 0
28 days after randomization
Secondary outcome [7] 388098 0
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] 388098 0
72 hours after randomization
Secondary outcome [8] 388099 0
ICU length of stay (through patient medical records)
Timepoint [8] 388099 0
90 days after randomization
Secondary outcome [9] 388100 0
Hospital length of stay (through patient medical records)
Timepoint [9] 388100 0
90 days after randomization
Secondary outcome [10] 388101 0
ICU mortality
Timepoint [10] 388101 0
90 days after randomization
Secondary outcome [11] 388102 0
Hospital mortality
Timepoint [11] 388102 0
90 days after randomization
Secondary outcome [12] 388103 0
28-day mortality
Timepoint [12] 388103 0
28 days after randomization
Secondary outcome [13] 388104 0
90-day mortality
Timepoint [13] 388104 0
90 days after randomization
Secondary outcome [14] 388105 0
28 day cumulative vasopressor free hours (through patient medical records)
Timepoint [14] 388105 0
28 days after randomization
Secondary outcome [15] 388106 0
28 day renal replacement therapy–free days (through patient medical records)
Timepoint [15] 388106 0
28 days after randomization
Secondary outcome [16] 388107 0
Hypokalaemia needing correction (defined as potassium level < 3.5 mEq/L needing correction, and assessed through patient medical records)
Timepoint [16] 388107 0
72 hours after randomisation
Secondary outcome [17] 388108 0
Hypocalcaemia needing correction (defined as ionized calcium level < 1.15 mmol/L needing correction, and assessed through patient medical records)
Timepoint [17] 388108 0
72 hours after randomisation
Secondary outcome [18] 388109 0
Dysnatraemia (Na > 155 mEq/L) (through patient medical records)
Timepoint [18] 388109 0
72 hours after randomisation
Secondary outcome [19] 388110 0
Strong in difference (SID) in the first 24 hours after the start of the infusion (through patient medical records)
Timepoint [19] 388110 0
24 hours after the start of the infusion
Secondary outcome [20] 388111 0
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] 388111 0
24 hours after the start of the infusion
Secondary outcome [21] 388112 0
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] 388112 0
24 hours after the start of the infusion
Secondary outcome [22] 388113 0
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] 388113 0
24 hours after the start of the infusion
Secondary outcome [23] 389104 0
Strong ion gap (SIG) in the first 24 hours after the start of the infusion (through patient medical records)
Timepoint [23] 389104 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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. Very likely to receive RRT within 6 hours; or
16. 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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17857 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 17858 0
The Alfred - Melbourne
Recruitment hospital [3] 17860 0
Western Hospital - Footscray - Footscray
Recruitment hospital [4] 17861 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [5] 17862 0
Sunshine Hospital - St Albans
Recruitment hospital [6] 17863 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [7] 17864 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [8] 17865 0
The Northern Hospital - Epping
Recruitment postcode(s) [1] 31715 0
3084 - Heidelberg
Recruitment postcode(s) [2] 31716 0
3004 - Melbourne
Recruitment postcode(s) [3] 31717 0
3052 - Parkville
Recruitment postcode(s) [4] 31718 0
3011 - Footscray
Recruitment postcode(s) [5] 31719 0
3021 - St Albans
Recruitment postcode(s) [6] 31720 0
3220 - Geelong
Recruitment postcode(s) [7] 31721 0
3168 - Clayton
Recruitment postcode(s) [8] 31722 0
3076 - Epping
Recruitment outside Australia
Country [1] 23069 0
New Zealand
State/province [1] 23069 0
Wellington
Country [2] 23070 0
Japan
State/province [2] 23070 0
Tokyo
Country [3] 23071 0
Brazil
State/province [3] 23071 0
São Paulo

Funding & Sponsors
Funding source category [1] 307031 0
Other
Name [1] 307031 0
Australian and New Zealand Intensive Care Research Centre
Address [1] 307031 0
Level 3
553 St Kilda Road
Melbourne
VIC 3004
Australia
Country [1] 307031 0
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] 307597 0
None
Name [1] 307597 0
Address [1] 307597 0
Country [1] 307597 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307161 0
Alfred Health Ethics Committee
Ethics committee address [1] 307161 0
55 Commercial Rd,
Melbourne
VIC 3004
Australia
Ethics committee country [1] 307161 0
Australia
Date submitted for ethics approval [1] 307161 0
16/11/2020
Approval date [1] 307161 0
Ethics approval number [1] 307161 0

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 106238 0
Prof Andrew Udy
Address 106238 0
Alfred Health
55 Commercial Road
Melbourne VIC 3004
PO Box 315 Prahran
VIC 3181 Australia
Country 106238 0
Australia
Phone 106238 0
+61 0 438 755 568
Fax 106238 0
Email 106238 0
andrew@udy.com
Contact person for public queries
Name 106239 0
Dr Ary Serpa Neto
Address 106239 0
Australian and New Zealand Intensive Care-Research Centre (ANZIC-RC)
Monash University
Level 3,
553 St Kilda Road
Melbourne,
VIC 3004
Country 106239 0
Australia
Phone 106239 0
+61 0 432 749 435
Fax 106239 0
Email 106239 0
ary.serpaneto@monash.edu
Contact person for scientific queries
Name 106240 0
Dr Ary Serpa Neto
Address 106240 0
Australian and New Zealand Intensive Care-Research Centre (ANZIC-RC)
Monash University
Level 3,
553 St Kilda Road
Melbourne,
VIC 3004
Country 106240 0
Australia
Phone 106240 0
+61 0 432 749 435
Fax 106240 0
Email 106240 0
ary.serpaneto@monash.edu

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 (ary.serpaneto@monash.edu)
What supporting documents are/will be available?
No other documents available
Summary results
No Results