REAMBERIN® 1.5% in Rehydration Therapy of Diabetic Ketoacidosis

Polysan

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Diabetic Ketoacidosis

Treatments: Drug: Placebo; Drug: Reamberin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06955416

RMB-II-III-DKA-2024

Details and patient eligibility

About

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.

Enrollment: 312 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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312 participants in 2 patient groups, including a placebo group

Reamberin

Experimental group

Description:

Infusion of study drug REAMBERIN® for 2 days or until resolution of diabetic ketoacidosis (DKA), whichever occurs first

Treatment:

Drug: Reamberin

Placebo

Placebo Comparator group

Description:

Infusion of 0,9% normal saline at the same volume for 2 days or until resolution of diabetic ketoacidosis (DKA), whichever occurs first

Treatment:

Drug: Placebo