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Efficacy and Safety of Rheosorbilact® Solution for Infusion, in a Complex Therapy of Pneumonia

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ClinicalTrials.gov Identifier: NCT03824457
Recruitment Status : Recruiting
First Posted : January 31, 2019
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
Yuria-Pharm

Tracking Information
First Submitted Date  ICMJE January 29, 2019
First Posted Date  ICMJE January 31, 2019
Last Update Posted Date July 4, 2019
Actual Study Start Date  ICMJE January 8, 2018
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
A change in the total SOFA score vs. baseline score upon admission; [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03824457 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
  • A change in the total APACHE II score vs. baseline score upon admission; [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Acute physiology and chronic health evaluation(APACHE) II score is calculated from a patient's age (0-6 points) and 12 physiological parameters (each item 0-4 points): AaDO2 or PaO2 (depending on FiO2), Temperature (rectal), Mean arterial pressure, pH arterial, Heart rate, Respiratory rate, Sodium (serum), Potassium (serum), Creatinine, Hematocrit, White blood cell count, Glasgow Coma Scale and chronic disease health status (0-5 points). The APACHE II score ranges from 0 to 71 points. We evaluate initial APACHE II score and differences between subsequent scores (Δ-APACHE II scores).
  • A change in the total SAPS II score vs. baseline score upon admission; [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    The SAPS II score is made of 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). The SAPS II score ranges from 0 to 160 points. We evaluate initial SAPS II score and differences between subsequent scores (Δ-SAPS II scores).
  • A change in the total MODS score vs. baseline score upon admission; [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    MODS (Multiple Organ Dysfunction 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 MODS score ranges from 0 to 24 points. We evaluate initial MODS score and differences between subsequent scores (MODS scores).
  • A change in the total PSI/PORT score vs. baseline score upon admission [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    The Pneumonia severity index (PSI or PORT Score) for predicting the mortality in patients with pneumonia based on patients stratification into five classes of risk for death. The lowest risk class (risk class I) comprises patients who are younger than 50 years of age, have none of the five important coexisting illnesses and have normal mental status and normal or only mildly abnormal vital signs at presentation. Assignment to the remaining risk classes depends on the presence or absence of a set of medical history, physical examination, and laboratory findings. Total point scores of 70 or less correspond to class II, 71-90 to class III, 91-130 to class IV, and more than 130 to class V.
  • A change in the total CURB-65 score vs. baseline score upon admission [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    The CURB-65 score for predicting the mortality in patients with pneumonia is an acronym for each of the six risk factors measured: confusion status, serum urea, respiratory rate, blood pressure, and age. Each risk factor scores one point, for a maximum score of 5.
  • Concentration of glucose [ Time Frame: 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 (mmol/L) in blood serum after 8-hour fasting.
  • Concentration of sodium [ Time Frame: 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 (mmol/L) in blood serum after 8-hour fasting.
  • Concentration of potassium [ Time Frame: 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 (mmol/L) in blood serum after 8-hour fasting.
  • Concentration of lactate [ Time Frame: 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 (mmol/L) in blood serum after 8-hour fasting.
  • Concentration of pyruvate [ Time Frame: 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 (mmol/L) in blood serum after 8-hour fasting.
  • Concentration of urea. [ Time Frame: 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 (mmol/L) in blood serum after 8-hour fasting.
  • Concentration of creatinine. [ Time Frame: 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 (µmol/L) in blood serum after 8-hour fasting.
  • Concentration of bilirubin. [ Time Frame: 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 (µmol/L) in blood serum after 8-hour fasting.
  • Concentration of alanine aminotransferase. [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of aspartate aminotransferase. [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of lactate dehydrogenase. [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of alkaline phosphatase. [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of γ-Glutamyltransferase. [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of low-molecular-weight adiponectin (LMW). [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of middle-molecular-weight adiponectin (MMW). [ Time Frame: 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 (U/L) in blood serum after 8-hour fasting.
  • Concentration of albumin. [ Time Frame: 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 in blood serum after 8-hour fasting.
  • Procalcitonin level. [ Time Frame: 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 procalcitonin level (µg/L) in blood serum after 8-hour fasting.
  • White blood cells (WBC) count level. [ Time Frame: 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 (billion/L) count level in blood serum after 8-hour fasting.
  • Lymphocyte count level. [ Time Frame: 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 in blood serum after 8-hour fasting.
  • Platelet count level. [ Time Frame: 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 (billion/L) in blood serum after 8-hour fasting. 2. assessment of ECG parameters; 3.parameters of central hemodynamics; 4. mental status: consciousness, intelligence, behavior, neuromuscular disorders.
  • Calculation of Nuclear index of intoxication (NII) [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Calculated by dividing the number of myelocytes, young and stab neutrophils by number of segmented neutrophils.
  • Calculation of Leukocyte index of intoxication (LII). [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Calculated by the formula of Kalf-Kalifa: correlation between the level of neutrophils and the content of other cells in the blood leukocytic composition.
  • Concentration of C-reactive protein (CRP). [ Time Frame: 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) in blood serum after 8-hour fasting.
  • Level of circulating immune complexes (CIC). [ Time Frame: 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) in blood serum after 8-hour fasting.
  • Concentration of Interleukin-1 and 2. [ Time Frame: 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 (pg/ml) and Interleukin-2 (pg/ml) in blood serum after 8-hour fasting.
  • Calculation of neutrophil-to-lymphocyte ratio (NLR). [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Calculated by dividing the number of neutrophils (%) by number of lymphocytes (%).
  • Concentration of immunoglobulins. [ Time Frame: 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 Ig A, Ig M and Ig G in blood serum after 8-hour fasting.
  • Concentration of complements. [ Time Frame: 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 (C3, C4) in blood sample after 8-hour fasting.
  • Assessment of central hemodynamics. [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Measurement of central venous pressure (mmh2o) in the central vein.
  • A change in the total Glasgow Coma Scale (GCS) score vs. baseline score upon admission [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    The GCS is composed of 3 components: ocular response (assessment 1-4 points), motor response (assessment 1-6 points) verbal response (evaluation of 1-5 points). Scores for each component are added together to get the total that will range between a minimum of 3 points (which corresponds to a patient who does not open his eyes and no motor response to stimulation or verbal response) and a maximum value of 15 points (corresponding to a patient with open eyes, obeying orders and maintaining a consistent language).
  • Measurement of 12-lead electrocardiogram (ECG) [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Measurement of 12-lead ECG with further evaluation and interpretation whether the ECG waves, intervals, durations and rhythm are normal.
  • Number of participants with Presence of clinical signs [ Time Frame: Will be evaluated for the duration of Intensive Care Unit (ICU) stay, at screening (Day 0) and Visit 3 (Day 3) of ICU stay. ]
    Number of participants with presence of clinical signs such as adynamia, weakness, memory impairment, sleep disorder, irritability, evaluated according to patient's subjective complaints.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 29, 2019)
  • Incidence of Treatment-Emergent Adverse events. [ Time Frame: Patients will be followed during 14 days. ]
    All types of adverse events.
  • Incidence of multiple organ failure. [ Time Frame: Patients will be followed during 14 days. ]
    Incidence of multiple organ failure.
  • Overall survival (%) at follow-up visit. [ Time Frame: Patients will be followed during 14 days. ]
    Overall survival (%) at follow-up visit.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Rheosorbilact® Solution for Infusion, in a Complex Therapy of Pneumonia
Official Title  ICMJE Open-label, Randomized, Controlled, With Blind Assessor, Study to Assess Efficacy and Safety of Rheosorbilact®, Solution for Infusion ("Yuria-Pharm"), in Comparison With Ringer's Lactate,Solution for Infusion, in a Complex Therapy of Pneumonia.
Brief Summary 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 pneumonia. Half of participants will receive Rheosorbilact® in complex therapy, while the other half will receive Ringer's Lactate in complex therapy.
Detailed Description

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.

Rheosorbilact® is administered to improve capillary blood flow for the prevention and treatment of traumatic, surgical, hemolytic, toxic and burn shock, acute blood loss, and burn disease; infectious diseases accompanied by intoxication, exacerbation of chronic hepatitis; sepsis, pre- and postoperative period to improve arterial and venous circulation for the prevention and treatment of thrombosis, thrombophlebitis, endarteritis, and Raynaud's disease.

Ringer's Lactate, solution for infusion will be used as a comparator. As a rehydrating agent, Ringer's Lactate has a detoxification effect, replenishes the deficiency of circulating blood volume, and stabilizes the water and electrolyte composition of blood. Ringer's Lactate normalizes the acid-base balance. Lactate is metabolized in the body to bicarbonate, so the solution has an alkalizing effect. With osmolarity at 273 mOsm/l, Ringer's Lactate is close to isotonic solution and is indicated for hypovolemia, isotonic dehydration, and metabolic alkalosis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
Outcomes Assessor will perform the assessment of primary, secondary efficasy and safety parameters
Primary Purpose: Treatment
Condition  ICMJE Pneumonia
Intervention  ICMJE
  • Drug: Rheosorbilact®
    Rheosorbilact® is administered as a part of the infusion therapy intravenously (with speed 40-60 drip per minute) at a dose of not more than 400 ml (6 to 7 ml/kg body weight per 24 hours) for 3 days.
  • Drug: Ringer lactate
    Rheosorbilact® is administered as a part of the infusion therapy intravenously (with speed 40-60 drip per minute) at a dose of not more than 400 ml (6 to 7 ml/kg body weight per 24 hours) for 3 days.
Study Arms  ICMJE
  • Experimental: Rheosorbilact®
    Rheosorbilact® is administered as a part of the infusion therapy intravenously (with speed 40-60 drip per minute) at a dose of not more than 400 ml (6 to 7 ml/kg body weight per 24 hours). The period of the treatment with the study drug lasts 3 days.
    Intervention: Drug: Rheosorbilact®
  • Active Comparator: Ringer 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 not more than 400 ml (6 to 7 ml/kg body weight per 24 hours).The period of the treatment with the active comparator lasts 3 days.
    Intervention: Drug: Ringer lactate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 29, 2019)
134
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2020
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men and women aged 18 to 45 years inclusive;
  2. Community-acquired pneumonia with a prescription from the beginning of antibacterial therapy no more than 48 hours;
  3. The risk class of pneumonia in the PSI/PORT index score is at least IV;
  4. Informed consent for participation in the study signed by subject's own hand.
  5. The baseline value of the SOFA scale ≥ 2 points.

Non-inclusion criteria:

  1. Individual intolerance of the components of the study drug and reference preparation;
  2. Hypersensitivity to sodium lactate;
  3. Intravenous infusions of lactate- or sorbitol-containing products within 24 hours before enrollment;
  4. Severe renal dysfunction (creatinine is more than 300 μmol/l or estimated creatinine clearance is less than 30 ml/min);
  5. Pregnancy or breast-feeding;
  6. Metabolic alkalosis;
  7. Severe metabolic acidosis;
  8. Intracerebral hemorrhage;
  9. Any thromboembolism;
  10. Decompensated cardiovascular failure;
  11. Arterial hypertension III st;
  12. Conditions associated with immunodeficiency (the use of cytostatics or system steroids, AIDS, diabetes mellitus);
  13. Extracellular hyperhydration or hypervolemia;
  14. Severe renal insuffiency (with oliguria/anuria);
  15. Hyperkalemia;
  16. Hypercalcemia;
  17. Ascites associated with cirrhosis;
  18. Conditions associated with increased lactate levels (hyperlactatemia > 2 mmol / l), including lactic acidosis, or impaired lactate uptake (including due severe hepatic insufficiency);
  19. Concomitant therapy with cardiac glycosides.

Exclusion Criteria:

  1. Infusion of the study drug or the comparator is started more than 12 hours after randomization;
  2. Lack of data for community-acquired pneumonia (diagnosis not confirmed);
  3. Withdrawal of the informed consent by the subject;
  4. Investigator considers that the infusion therapy with either study drug or comparator may not be continued for safety reasons;
  5. Development of conditions that prevent further use of the study drug/comparator before efficacy evaluation visit (Visit 3);
  6. Subject needs concomitant therapy prohibited in the study before efficacy evaluation visit (Visit 3);
  7. Development of conditions (including serious adverse events) which make it impossible to evaluate the primary endpoint;
  8. Confirmation of pregnancy at any time of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Viktoriia Osiichuk 503417129 ext +380 viktoriia.osiichuk@uf.ua
Contact: Maryna Bahmet 504927528 ext +380 maryna.bahmet@uf.ua
Listed Location Countries  ICMJE Kazakhstan,   Georgia,   Moldova, Republic of,   Ukraine,   Uzbekistan,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03824457
Other Study ID Numbers  ICMJE RheoSTAT-CP0698
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Yuria-Pharm
Study Sponsor  ICMJE Yuria-Pharm
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Yuria-Pharm
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP