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

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Acidosis
• Intervention / Treatment: Drug: Meglumine Sodium Succinate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangel'sk, Russian Federation, 163001
    • GBUZ Arkhangelsk region "First GKB named after E.E. Volosevich"
  • Ivanovo, Russian Federation, 152040
    • Ivanovo Regional Clinical Hospital
  • Moscow, Russian Federation
    • Central Clinical Hospital with a polyclinic of the Office of the President of the Russian Federation
  • Nizhny Novgorod, Russian Federation, 603001
    • Privolzhsky District Medical Center
  • Saint Petersburg, Russian Federation
    • Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
  • Saransk, Russian Federation, 430005
    • National Research Mordovian State University n.a. N.P. Ogarev

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed and dated written Informed Consent (if unconscious due to a critical condition, the decision is made by a Council consisting of 3 physicians)
2. Male and female patients aged 18-70
3. 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
4. pH of arterial blood 7.20-7.35, inclusive
5. Planned volume of infusion >= 1500 ml per day
6. Interval between admission to the ICU and randomization <24 hours

Exclusion Criteria:

1. Pregnant and lactating women
2. Known hypersensitivity to any component of the study drug / placebo
3. Chronic kidney disease stage C5 (end-stage renal failure)
4. Acute hepatic failure (ALT > 15 upper normal limits) or liver cirrhosis
5. Traumatic brain injury accompanied by cerebral edema
6. Previously diagnosed mental illness
7. Any chronic disease in the terminal stage with a life expectancy of < 3 months
8. HIV infection
9. 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)
10. Extremely low or extremely high body fat
11. Infusion sodium bicarbonate, sodium bicarbonate, trometamol, Sterofundin, Quintasol, Ringer's lactate (Hartmann's solution) within 6 hours before screening
12. Acute respiratory acidosis
13. Poisoning with chemical compounds causing metabolic acidosis
14. Alcohol in saliva at screening >= 0.5 pro mille
15. Previously diagnosed chronic obstructive pulmonary disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
• Collaborators: Atlant Clinical Ltd.
• Investigators: Principal Investigator: Mikhail Yu Kirov, GBUZ Arkhangelsk region "First GKB named after E.E. Volosevich"

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: critical illness; metabolic acidosis; acid-base disorder
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis
• Other Study ID Numbers: RB-II-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No