Clinical trial NCT06955416: A Multicenter, Randomized, Double-blind Study of REAMBERIN® 1.5% in Rehydration Therapy of Diabetic Ketoacidosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Diabetic Ketoacidosis
Lead sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2025-05-02
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multicenter, prospective, two-stage, comparative, randomized, double-blind, parallel-group study with an adaptive design.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time from initiation of therapy to resolution of diabetic ketoacidosis (DKA)
timeFrame: 48 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Arkhangelsk
country: Russian Federation
facility: State Budgetary Institution of Healthcare of the Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich"
city: Ivanovo
country: Russian Federation
facility: Regional budgetary healthcare institution "Ivanovo regional clinical hospital"
city: Kemerovo
country: Russian Federation
facility: Kuzbass Clinical Hospital of Emergency Medical Care named after M.A. Podgorbunsky
Study officials:
affiliation: STPF "POLYSAN"
name: Tatiana Kharitonova, MD, PhD
role: STUDY_DIRECTOR
References: