Clinical trial NCT05697770: SODium BICarbonate for Metabolic Acidosis in the ICU
Official title: SODium BICarbonate for Metabolic Acidosis in the Intensive Care Unit (SODa-BIC): a Multicentre, Randomised, Double-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metabolic Acidosis
Shock
Keywords: Sodium bicarbonate
Metabolic acidosis
Shock
Clinical trial
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomly allocated in a 1:1 ratio to receive either an infusion of D5W + sodium bicarbonate, or D5W alone.
Primary purpose: TREATMENT

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 \&gt; 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 \&lt; 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.

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.

Primary outcomes:
measure: MAKE30 score
timeFrame: 30 days or at hospital discharge (whichever occurs first)
Secondary outcomes:
measure: 30-day in-hospital mortality
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: Receipt of renal replacement therapy in the first 30 days
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: Persistent renal dysfunction
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: Renal replacement therapy dependence at day 30
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: ICU mortality
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: Hospital mortality
timeFrame: 90 days or at hospital discharge (whichever occurs first)
measure: 90-day in-hospital mortality
timeFrame: 90 days or at hospital discharge (whichever occurs first)
Other outcomes:
measure: Recurrence of metabolic acidosis in the first 7 days after randomization
timeFrame: 7 days after randomization
measure: Incidence and the maximum stage of AKI in the first 7 days after randomization
timeFrame: 7 days after randomization
measure: Vasopressor-free days at day 30
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: Renal replacement therapy-free days at day 30
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: ICU-free days at day 30
timeFrame: 30 days or at hospital discharge (whichever occurs first)
measure: Hospital-free days at day 90
timeFrame: 90 days or at hospital discharge (whichever occurs first)
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Tiwi
country: Australia
facility: Royal Darwin Hospital
state: Northern Territory
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Coopers Plains
country: Australia
facility: Queen Elizabeth II Jubilee Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hopsital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Ballarat
country: Australia
facility: Grapmians Health
state: Victoria
city: Berwick
country: Australia
facility: Casey Hospital
state: Victoria
city: Footscray
country: Australia
facility: Footscray Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: The Austin Hospital
state: Victoria
city: Langwarrin
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Richmond
country: Australia
facility: Epworth
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital
city: Seeb
country: Oman
facility: Sultan Qaboos Comprehensive Cancer Care and Research Center
Study officials:
affiliation: ANZIC RC, Monash university
name: Ary Serpa Neto, PhD
role: PRINCIPAL_INVESTIGATOR
References: