Open-label, Randomized, Controlled, With Blind Assessor, Study to Assess Efficacy and Safety of Rheosorbilact®, Solution for Infusion, in Comparison With Ringer's Lactate, Solution for Infusion, in a Complex Therapy of Sepsis.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 13
- 主要终点
- A change in the total SOFA score vs. baseline score upon admission;
研究概览
简要总结
This study evaluates the efficacy and safety of Rheosorbilact®, solution for infusion ("Yuria-Pharm" LLC), in comparison with Ringer's Lactate, solution for infusion, in a complex therapy of sepsis. Half of participants will receive Rheosorbilact® in complex therapy, while the other half will receive Ringer's Lactate in complex therapy.
详细描述
Rheosorbilact® has rheological, anti-shock, detoxification, and alkalizing effects. Sorbitol and sodium lactate are the major pharmacologically active ingredients. In the liver, sorbitol is first converted into fructose, which is then converted into glucose, and then into glycogen. Part of sorbitol is used for urgent energy needs, while the other part is kept as a reserve in the form of glycogen. Isotonic sorbitol solution has a disaggregating effect and, therefore, improves microcirculation and tissue perfusion.
The management of metabolic acidosis with sodium lactate goes more slowly compared to bicarbonate solution, as far as sodium lactate enters the metabolic process; however the latter does not cause swings in pH values. The effect of sodium lactate is typically seen 20 to 30 minutes after administration.
Sodium chloride is a plasma-substituting agent that exhibits a detoxification and rehydration effect. It replenishes the deficiency of sodium and chlorine ions in various pathological conditions.
Calcium chloride replenishes deficiency of calcium ions. Calcium ions are essential in the transmission of nerve impulses, contraction of skeletal and smooth muscles, myocardial activity, bone tissue formation, and blood clotting. It reduces the permeability of cells and vascular walls, prevents the development of inflammatory reactions, enhances the resistance of the body to infections and can significantly boost phagocytosis.
Potassium chloride restores the water-electrolyte balance. It exhibits a negative chrono- and bathmotropic action and, when administered in high doses, has a negative ino- and dromotropic and moderate diuretic effect. It is involved in the process of nerve impulse conduction, increases the content of acetylcholine and causes excitation of the sympathetic segment of the autonomic nervous system and improves the contraction of skeletal muscles in subjects with muscular dystrophy or myasthenia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Outcomes Assessor will perform the assessment of primary, secondary efficasy and safety parameters
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female aged 18 to 60 years inclusive
- •Sepsis diagnosed according to ACCP / SCCM criteria (no later than 24 hours from the time of diagnosis of sepsis to screening visit) (Annex 1: Sequence Diagnostic Criteria for SCCM / ESICM / ACCP / ATS / SIS)
- •Informed consent for participation in the study signed by subject's own hand.
- •The baseline value of the SOFA scale ≥ 2 points.
- •Non-inclusion Criteria:
- •The presence of any of the criteria for severe sepsis by ACCP / SCCM (presence of signs of organ failure - Annex 1: criteria for diagnosis of sepsis SCCM / ESICM / ACCP / ATS / SIS)
- •Individual intolerance of the components of the study drug and the comparator;
- •Hypersensitivity to sodium lactate;
- •Intravenous infusions of lactate- or sorbitol-containing products within 24 hours before enrollment;
- •Pregnancy or breast-feeding;
- •Severe renal dysfunction (creatinine is more than 300 μmol/l or estimated creatinine clearance is less than 30 ml/min);
- •Metabolic alkalosis;
- •Severe metabolic acidosis;
- •Intracerebral hemorrhage;
- •Any thromboembolism;
- •Decompensated cardiovascular failure;
- •Arterial hypertension III st;
- •Conditions associated with immunodeficiency (the use of cytostatics or system steroids, AIDS);
- •Extracellular hyperhydration or hypervolemia;
- •Severe renal insuffiency (with oliguria / anuria);
- •Hyperkalaemia;
- •Hypercalcemia;
- •Ascites associated with cirrhosis;
- •Conditions associated with increased lactate levels (hyperlactatemia > 2 mmol / l), including lactic acidosis, or impaired lactate uptake (including due severe hepatic insufficiency);
- •Concomitant therapy with cardiac glycosides;
排除标准
- •Infusion of the study drug or the comparator is started more than 12 hours after randomization;
- •Lack of data for sepsis (diagnosis not confirmed);
- •Withdrawal of the informed consent by the subject;
- •Investigator considers that the infusion therapy with either study drug or comparator may not be continued for safety reasons;
- •Development of conditions that prevent further use of the study drug/comparator before efficacy evaluation visit (Visit 3);
- •Subject needs concomitant therapy prohibited in the study before efficacy evaluation visit (Visit 3);
- •Development of conditions (including serious adverse events) which make it impossible to evaluate the primary endpoint;
- •Confirmation of pregnancy at any time of the study.
研究组 & 干预措施
Rheosorbilact®
Rheosorbilact® is administered as a part of the infusion therapy intravenously (with speed 40-60 drip per minute) at a dose of 600 to 1,000 ml (10 to 15 ml/kg body weight per 24 hours).The period of the treatment with the study drug lasts 3 days.
干预措施: Rheosorbilact® (Drug)
Ringer's Lactate
Ringer's Lactate is administered as a part of the infusion therapy intravenously (with speed 40-60 drip per minute) at a dose of 1,000 to 2,500 ml (15 to 40 ml/kg body weight per 24 hours).The period of the treatment with the active comparator lasts 3 days.
干预措施: Ringer lactate (Drug)
结局指标
主要结局
A change in the total SOFA score vs. baseline score upon admission;
时间窗: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.
Sequential Organ Failure Assessment (SOFA) score is composed of scores of six organ systems: R-respiratory, C-cardiovascular, H-hepatic, Co-coagulation, Re-renal, and N-neurological graded from 0 to 4 according to the degree of dysfunction or failure. The SOFA score ranges from 0 to 24 points. We evaluate initial SOFA score and differences between subsequent scores (Δ-SOFA scores).
次要结局
- A change in the total APACHE II score vs. baseline score upon admission;(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of potassium(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of pyruvate(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of bilirubin(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- A change in the total MODS score vs. baseline score upon admission(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of creatinine(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of lactate dehydrogenase(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of sodium(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of lactate(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of urea(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of alanine aminotransferase(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of alkaline phosphatase(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of creatine kinase(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of γ-Glutamyltransferase(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of low-molecular-weight adiponectin (LMW)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of albumin(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- A change in the total SAPS II score vs. baseline score upon admission(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of glucose(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Platelet count level(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Procalcitonin level(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Level of circulating immune complexes (CIC)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of Interleukin-1 and 2(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Calculation of neutrophil-to-lymphocyte ratio (NLR)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Assessment of central hemodynamics(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Clinical signs(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of aspartate aminotransferase(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Lymphocyte count level(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Calculation of Leukocyte index of intoxication (LII)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of immunoglobulins(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of complements(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- A change in the total Glasgow Coma Scale (GCS) score vs. baseline score upon admission(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of middle-molecular-weight adiponectin (MMW)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- White blood cells (WBC) count level(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Assessment of electrocardiogram (ECG)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Calculation of Nuclear index of intoxication (NII)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)
- Concentration of C-reactive protein (CRP)(Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay.)