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

NCT ID: NCT03764085

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-06
• Study Completion Date: 2019-12-11

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.

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.

Conditions

Sepsis; Intoxication; Septic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Rheosorbilact®

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Ringer lactate

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yuria-Pharm

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

"Unimedi Adjara" LLC

Batumi, , Georgia

Kutaisi Referral Hospital

Kutaisi, , Georgia

Hospital of the Medical Center of the Administration of the President of the Republic of Kazakhstan

Astana, , Kazakhstan

Institute of Ambulance

Chisinau, , Moldova

Municipal Clinical Hospital "Sfinta Treime"

Chisinau, , Moldova

Republican Clinical Hospital

Chisinau, , Moldova

Dnipro's Medical Academy of Ministry of Health of Ukraine

Dnipro, , Ukraine

Zaicev's Institute of general and urgent surgery NMA Ukraine

Kharkiv, , Ukraine

Khmelnytskyi Regional Clinical Hospital

Khmelnytskyi, , Ukraine

HSEE of Ukraine "Ukrainian Medical Stomatological Academy"; Poltava Central District Hospital

Poltava, , Ukraine

Central District Clinical Hospital

Vinnitsa, , Ukraine

Zaporizka Medical Academy of postgraduate education, Zaporizkyi Clinical Hospital N9

Zaporizhzhya, , Ukraine

Republic Centre of Ambulance

Tashkent, , Uzbekistan

Countries

Georgia; Kazakhstan; Moldova; Ukraine; Uzbekistan

Other Identifiers

RheoSTAT-CP0620

Identifier Type: -

Identifier Source: org_study_id