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

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ClinicalTrials.gov Identifier: NCT03764085
Recruitment Status : Recruiting
First Posted : December 4, 2018
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Yuria-Pharm

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 sepsis. Half of participants will receive Rheosorbilact® in complex therapy, while the other half will receive Ringer's Lactate in complex therapy.

Condition or disease Intervention/treatment Phase
Sepsis Intoxication; Septic Drug: Rheosorbilact® Drug: Ringer lactate Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Outcomes Assessor will perform the assessment of primary, secondary efficasy and safety parameters
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : December 6, 2016
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: 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.
Drug: Rheosorbilact®
Administered 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) for 3 days.

Active Comparator: 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.
Drug: Ringer lactate
Administered 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) for 3 days.




Primary Outcome Measures :
  1. 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).



Secondary Outcome Measures :
  1. 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).


  2. 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).


  3. 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).


  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Concentration of creatine kinase [ 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 creatine kinase (U/L) in blood serum after 8-hour fasting.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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

  23. 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

  24. 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

  25. 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.

  26. 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.

  27. 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

  28. 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

  29. 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

  30. 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 (%).

  31. 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

  32. 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

  33. 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

  34. 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).

  35. Assessment of 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. ]
    Presence of clinically significant changes on ECG is evaluated.

  36. 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. ]
    Presence of clinical signs (adynamia, weakness, memory impairment, sleep disorder, irritability) is based on patient's subjective complaints.


Other Outcome Measures:
  1. Incidence of Treatment-Emergent Adverse events [ Time Frame: Patients will be followed during 14 days. ]
    All types of adverse events

  2. Incidence of multiple organ failure [ Time Frame: Patients will be followed during 14 days. ]
    Incidence of multiple organ failure

  3. Overall survival (%) at follow-up visit. [ Time Frame: Follow-up visit (Day 14±1) ]
    Overall survival (%) at follow-up visit.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female aged 18 to 60 years inclusive
  2. 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)
  3. Informed consent for participation in the study signed by subject's own hand.
  4. The baseline value of the SOFA scale ≥ 2 points.

Non-inclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03764085


Contacts
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Contact: Viktoriia Osiichuk 503417129 ext +380 viktoriia.osiichuk@uf.ua
Contact: Maryna Bahmet 504927528 ext +380 maryna.bahmet@uf.ua

Locations
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Georgia
"Unimedi Adjara" LLC Recruiting
Batumi, Georgia
Contact: Sophio Beridze         
Kutaisi Referral Hospital Recruiting
Kutaisi, Georgia
Contact: Nino Babunashvili         
"Unimedi Kakheti" Ltd Active, not recruiting
Telavi, Georgia
Kazakhstan
Hospital of the Medical Center of the Administration of the President of the Republic of Kazakhstan Recruiting
Astana, Kazakhstan
Contact: Nasrulla Shanazarov         
Moldova, Republic of
Institute of Ambulance Recruiting
Chisinau, Moldova, Republic of
Contact: Adrian Belyy         
Municipal Clinical Hospital "Sfinta Treime" Recruiting
Chisinau, Moldova, Republic of
Contact: Ion Pyrtsak         
Republican Clinical Hospital Recruiting
Chisinau, Moldova, Republic of
Contact: Victor Cojocaru         
State Clinical Hospital of Traumatology and Orthopedy Active, not recruiting
Chisinau, Moldova, Republic of
Ukraine
Dnipro`s Medical Academy of Ministry of Health of Ukraine Recruiting
Dnipro, Ukraine, 49005
Contact: Yurii Kobelyatsky         
Zaicev's Institute of general and urgent surgery NMA Ukraine Recruiting
Kharkiv, Ukraine, 61018
Contact: Stanislav Peev         
Khmelnytskyi Regional Clinical Hospital Recruiting
Khmelnytskyi, Ukraine, 29000
Contact: Andrey Sapozhnik         
HSEE of Ukraine "Ukrainian Medical Stomatological Academy"; Poltava Central District Hospital Active, not recruiting
Poltava, Ukraine
Central District Clinical Hospital Recruiting
Vinnitsa, Ukraine, 21029
Contact: Oleg Kanikovsky         
Zaporizka Medical Academy of postgraduate education, Zaporizkyi Clinical Hospital N9 Recruiting
Zaporizhzhya, Ukraine, 69065
Contact: Volodymyr Koshlya         
Uzbekistan
Republic Centre of Ambulance Recruiting
Tashkent, Uzbekistan
Contact: Vіsolat Sharipova         
Sponsors and Collaborators
Yuria-Pharm

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Responsible Party: Yuria-Pharm
ClinicalTrials.gov Identifier: NCT03764085     History of Changes
Other Study ID Numbers: RheoSTAT-CP0620
First Posted: December 4, 2018    Key Record Dates
Last Update Posted: February 26, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Pharmaceutical Solutions