SODium BICarbonate for Metabolic Acidosis in the ICU

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Metabolic Acidosis, Shock

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Drug: 5% Dextrose


Participation Criteria
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Eligibility Criteria
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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. Adults (≥ 18 years); 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); A dedicated intravenous line (central or peripheral) is available (or insertion of such a line is planned within the next hour); and Metabolic acidosis, defined as: pH < 7.30; and BE ≤ -4 mEq/L; and PaCO2 ≤ 45 mmHg. Exclusion Criteria: Fulfilled all eligibility criteria greater than 48 hours ago; or 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 DKA; or Estimated glomerular filtration rate (eGFR) < 30 mL/min due to chronic kidney disease; or Currently receiving sodium bicarbonate at the moment of randomisation (doses of sodium bicarbonate prior to randomisation are allowed); or Currently receiving RRT (acute or chronic) or planned to start RRT in the next 3 hours (according to the treating clinical team); or Severe dysnatraemia (serum Na ≥ 155 mEq/L or < 120 mEq/L); or Hypokalaemia (serum K < 2.5 mEq/L); or Pulmonary oedema with PaO2 / FiO2 < 100; or Hypocalcaemia (iCa < 0.8mmol/L); or Patients admitted to the ICU after a drug overdose or intoxication (including alcohol intoxication); or Pregnancy or breastfeeding; or 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 Patients with a life expectancy < 30 days due to a chronic or underlying medical condition; or Considered to be at high risk of cerebral oedema by the treating clinician (e.g. traumatic brain injury or acute brain disease); or Clinician believes that being enrolled in intervention or control arm is not in the best interest of the patient; or Previous enrolment in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly allocated in a 1:1 ratio to receive either an infusion of D5W + sodium bicarbonate, or D5W alone.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium bicarbonate<br>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). | Drug: Sodium bicarbonate<br>* 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.<br>|
| Active Comparator: 5% dextrose<br>Standard 500 mL bag of D5W. | Drug: 5% Dextrose<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day in-hospital mortality | All-cause in-hospital mortality at day 30 | 30 days or at hospital discharge (whichever occurs first) | 
| 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) | 
| Persistent renal dysfunction | Defined as an elevation of the creatinine level to ≥ 200% of baseline | 30 days or at hospital discharge (whichever occurs first) | 
| 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) | 
| ICU mortality | All-cause ICU mortality at day 30 | 30 days or at hospital discharge (whichever occurs first) | 
| Hospital mortality | All-cause hospital mortality at day 90 | 90 days or at hospital discharge (whichever occurs first) | 
| 90-day in-hospital mortality | All-cause mortality at day 90 | 90 days or at hospital discharge (whichever occurs first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sodium bicarbonate, Metabolic acidosis, Shock, Clinical trial