Diabetic Ketoacidosis
Conditions
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.
Interventions
DRUGReamberin
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.
DRUGPlacebo
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.
Sponsors
POLYSAN Scientific & Technological Pharmaceutical Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
A multicenter, prospective, two-stage, comparative, randomized, double-blind, parallel-group study with an adaptive design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from initiation of therapy to resolution of diabetic ketoacidosis (DKA) | 48 hours | 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. |
Countries
Russia
Contacts
Primary ContactAlexey Kovalenko, Doc Biol Sci
Outcome results
None listed