REAMBERIN® 1.5% in Rehydration Therapy of Diabetic Ketoacidosis

A Multicenter, Randomized, Double-blind Study of the Safety and Efficacy of REAMBERIN®, 1.5% Solution for Infusions, in Addition to Standard Rehydration Therapy in Patients With Diabetic Ketoacidosis

A number of scientific papers have been published on the efficacy and safety of adding REAMBERIN® (meglumin sodium succinate), a 1.5% infusion solution, to standard therapy for patients with diabetic ketoacidosis (DKA), which showed that the addition of the medication to DKA therapy at a dose of 10 ml/kg/day or an average of 800.68±151.59 ml on the first day of infusion, leads to a more rapid and successful resolution of DKA, achieving a state of compensation, a more rapid transfer of the patient from the intensive care unit (ICU) and discharge from the hospital.

A combined, two-stage, multicenter, randomized, double-blind, phase II/III study with an adaptive design is planned. Stage 1 (phase II) will be a sequential evaluation of 2 doses of the study medication (750 ml and 1500 ml) versus placebo. At the 2nd stage of the study (phase III), additional recruitment of patients will be carried out in two groups in a 1:1 ratio to the experimental group or placebo group, to receive the optimal dose in accordance with the result obtained at stage 1.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Ketoacidosis
• Intervention / Treatment: Drug: Reamberin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Alexey Kovalenko, Doc Biol Sci; Phone Number: 212 +78127108225; Email: science@polysan.ru

Study Locations

• Russian Federation
  • Arkhangelsk, Russian Federation
    • Recruiting
    • State Budgetary Institution of Healthcare of the Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich"
    • Contact: Mikhail Yu Kirov, prof.; Phone Number: +7 (921)721-56-91; Email: mikhail_kirov@hotmail.com
    • Principal Investigator: Mikhail Yurievich Kirov, prof.
  • Ivanovo, Russian Federation
    • Recruiting
    • Regional budgetary healthcare institution "Ivanovo regional clinical hospital"
    • Contact: Tatyana A Bragina; Phone Number: +7 910 995 85 33; Email: doctorbragina@rambler.ru
    • Principal Investigator: Tatyana Alexandrovna Bragina
  • Kemerovo, Russian Federation
    • Recruiting
    • Kuzbass Clinical Hospital of Emergency Medical Care named after M.A. Podgorbunsky
    • Contact: Tatyana Elenskaya, MD, Cand.Med.Sci.; Phone Number: +7-384-2-46-51-52; Email: endokr@mail.ru
    • Principal Investigator: Tatyana Elenskaya

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed Informed Consent
• Male and female patients aged 18-75 years, inclusive.
• Confirmed diagnosis of type 1 or type 2 diabetes mellitus
• Established clinical diagnosis of DKA at the time of admission
• Plasma glucose > 13.9 mmol / l
• Metabolic acidosis (venous blood pH < 7.25)
• Serum bicarbonate < 18 mmol / l
• Ketonuria ≥ ++
• Possibility of randomizing the patient within 2 hours from admission to the hospital.

Exclusion Criteria:

• Known hypersensitivity to any component of the study drug/standard therapy p
• Blood pH ≤ 6.9 or standard bicarbonate level <5 mmol/l
• Previous use of other solutions containing reserve alkalinity carriers (acetate, lactate, malate, fumarate, etc).
• Conditions requiring emergency surgical intervention
• Abdominal surgeries in the last 14 days
• Traumatic brain injury accompanied by cerebral edema.
• Chronic treatment with steroids, atypical antipsychotics, cancer chemotherapy.
• Acute kidney injury
• Chronic kidney disease stage C5
• Liver injury (increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels by more than 5 times the established reference values).
• Acute pancreatitis
• Sepsis
• Severe multiple or combined trauma
• History of malignancy
• Clinically significant cardiovascular diseases (acute coronary syndrome; acute cerebrovascular accident (CVA) or transient ischemic attack (TIA); chronic heart failure class III - IV according to the NYHA classification; severe uncontrolled arrhythmia).
• Body mass index >=40.0
• Alcohol abuse, drug use, drug use.
• Other specific types of diabetes mellitus.
• Previously diagnosed mental illness
• Participation in another clinical trial or the use of drugs/dietary supplements containing succinic acid less than 30 days before inclusion in this study.
• Pregnancy or breastfeeding.
• SARS-CoV-2 infection
• Low systolic blood pressure (BP) (≤70 mmHg) upon admission to hospital or at the time of inclusion in the study.
• Contraindications to the infusion of REAMBERIN of 0.9% sodium chloride solution.

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; Infusion of study drug REAMBERIN® for 2 days or until resolution of diabetic ketoacidosis (DKA), whichever occurs first	Drug: Reamberin; Infusion of study drug REAMBERIN®, solution for infusion 1.5%, in a volume of 750-1500 ml per day (in accordance with the optimal dose established in stage 1), for 2 days or until resolution of DKA, whatever occurs earlier.
Placebo Comparator: Placebo; Infusion of 0,9% normal saline at the same volume for 2 days or until resolution of diabetic ketoacidosis (DKA), whichever occurs first	Drug: Placebo; Infusion of 0,9% normal saline in a volume of 750-1500 ml per day (in accordance with the optimal dose established in stage 1), for 2 days or until resolution of DKA, whatever occurs earlier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from initiation of therapy to resolution of diabetic ketoacidosis (DKA)	Time from the start of therapy with the study drug/placebo as part of standard therapy until resolution of DKA, hours. Criteria for resolution of DKA: plasma glucose level <11 mmol/l and at least two of the three acid-base balance indicators: bicarbonate ≥ 18 mmol/l, venous pH ≥ 7.3, anion gap ≤ 12 mmol/l.	48 hours

Collaborators and Investigators

• Sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
• Investigators: Study Director: Tatiana Kharitonova, MD, PhD, STPF "POLYSAN"

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 24, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 2, 2025

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Diabetes Mellitus; Diabetes Complications; Acid-Base Imbalance; Acidosis; Ketosis; Diabetic Ketoacidosis
• Other Study ID Numbers: RMB-II-III-DKA-2024

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