Meglimine Sodium Succinate for Correction of Metabolic Acidosis in Critically Ill Patients

Study Overview
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Brief Summary
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An acid-base imbalance, called metabolic acidosis (acid-base disorder lasting from several minutes to several days, caused by a decrease in serum bicarbonate ion (HCO3) concentration), is often observed in critically ill patients with various underlying diseases. Metabolic acidosis has a negative impact on the cardiovascular, respiratory, digestive, nervous, excretory, hematological, endocrine, musculoskeletal and immune systems and is associated with unfavourable outcomes. Reamberin® is a solution of disubstituted sodium salt of succinic acid, which has an alkaline reaction and succinate is capable to integrate into the Krebs cycle and restore energy metabolism in the cell. The aim of the present study is to evaluate the efficacy and safety of meglumine sodium succinate at a dose of 500 to 3000 ml in critically ill patients with metabolic acidosis and choose the optimal volume of its solution for the correction of metabolic acidosis in critically ill patients.

Official Title
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Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of REAMBERIN® (Meglumine Sodium Succinate) Used for Correction of Metabolic Acidosis in Critically Ill Patients

Conditions
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Metabolic Acidosis

Intervention / Treatment
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* Drug: Meglumine Sodium Succinate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written Informed Consent (if unconscious due to a critical condition, the decision is made by a Council consisting of 3 physicians) Male and female patients aged 18-70 Critical illness ((shock (including traumatic, hypovolemic), major trauma, acute massive blood loss, acute complicated surgical diseases of the abdominal organs) accompanied by metabolic acidosis, defined as serum bicarbonate <22mmol/L pH of arterial blood 7.20-7.35, inclusive Planned volume of infusion >= 1500 ml per day Interval between admission to the ICU and randomization <24 hours Exclusion Criteria: Pregnant and lactating women Known hypersensitivity to any component of the study drug / placebo Chronic kidney disease stage C5 (end-stage renal failure) Acute hepatic failure (ALT > 15 upper normal limits) or liver cirrhosis Traumatic brain injury accompanied by cerebral edema Previously diagnosed mental illness Any chronic disease in the terminal stage with a life expectancy of < 3 months HIV infection Clinically significant cardiovascular disease (unstable angina pectoris or angina pectoris of functional class III or higher; chronic heart failure III - IV class according to NYHA; acute myocardial infarction within 6 months before screening) Extremely low or extremely high body fat Infusion sodium bicarbonate, sodium bicarbonate, trometamol, Sterofundin, Quintasol, Ringer's lactate (Hartmann's solution) within 6 hours before screening Acute respiratory acidosis Poisoning with chemical compounds causing metabolic acidosis Alcohol in saliva at screening >= 0.5 pro mille Previously diagnosed chronic obstructive pulmonary disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reamberin group<br>Patients receive the investigational treatment (meglumine sodium succinate), 500 ml intravenously every 8 hours (up to 6 infusions). | Drug: Meglumine Sodium Succinate<br>* 500 ml of 1.4% solution IV at a rate of at least 4 ml and not more than 10 ml per minute<br>|
| Placebo Comparator: Placebo<br>Patients receive a Placebo (Ringer's solution), 500 ml intravenously every 8 hours (up to 6 infusions). | Drug: Placebo<br>* Ringer's solution, 500 ml IV at a rate of at least 4 ml and not more than 10 ml per minute<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elimination of acidosis at 24 hours after the start of treatment | The proportion of patients who have achieved normalization of the serum bicarbonate level (normalization = serum hydrocarbonate ion concentration ≥22 mmol / Liter), at 24 hours after the start of therapy. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolic acidosis, critical illness, acid-base disorder