Cytoflavin in the Rehabilitation of Post-intensive Care Syndrome in Stroke Survivors

Study Overview
=================
Brief Summary
-----------------
Objective - to assess the effect of Cytoflavin® and its tolerability within the integrated program of rehabilitation of patients who underwent ischemic stroke

Detailed Description
-----------------
Cerebral stroke (CS) remains one of the key issues of modern society, being a predominant cause of deep and persistent disability of the population. Huge social and economic damage arising from cerebrovascular diseases raises the problem of improving medical care for strokes among the most relevant scientific and practical tasks of neurology Regulation of energy metabolism is considered a powerful tool for acute conditions relief, including those that occur due to acute impairment of cerebral blood flow. A number of adjuvant energy protector concomitant medications with systemic pharmacodynamic properties based on signaling (hormonal) and substrate mode of action of succinic acid and other mitochondrial substrates and co-factors was created for this A significant role in the rehabilitation of patients who underwent CS is assigned to the treatment of complications of care in the intensive care unit, the so-called post-intensive care syndrome (PICS), which is a set of somatic, neurological, social and psychological consequences of periods in intensive care unit (ICU) conditions that bring limitations to the patient's daily activities In the Brain Institute Clinic (Ekaterinburg), the first results of the metabolic status monitoring during physical and cognitive exercise in patients with PICS were obtained. These results prove that control over metabolic state holds the promise of developing approaches to increasing exercise tolerance Taking into account the effectiveness of Cytoflavin® in treatment of acute impairment of cerebral circulation and consequences of cerebrovascular diseases, on the one hand, and its classification as a metabotropic energy corrector, on the other hand, the evaluation of Cytoflavin® medication tolerability in the integrated program of neurorehabilitation of patients with PICS after ischemic stroke presents a significant interest.

Official Title
-----------------
Use of Cytoflavin Solution at the Time of Early Rehabilitation in Patients With Post-intensive Care Syndrome Who Underwent Ischemic Stroke

Conditions
-----------------
Ischemic Stroke, Post Intensive Care Unit Syndrome

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged 18 years and above; Patients who underwent ischemic stroke; The period from the development of ischemic stroke is not less than 12 and not more than 28 days; Staying in intensive care unit for no less than 72 hours; Diagnosed post-intensive care syndrome (PICS); Functional status assessed using the modified Rankin scale amounts to 4-5; Gravity gradient of 20° to 40° upon inclusion in observational non-interventional program Exclusion Criteria: Vegetative state; Mechanical ventilation lasting more than 72 hours after the development of ischemic stroke; Surgical treatment for cerebral stroke (decompressive craniectomy; thromboextraction etc.); Premorbid (before the development of ischemic stroke) level of functional activity assessed using the modified Rankin scale amounts to 4 or 5; Signs of increasing neurological deficit or enlargement of hypoperfusion zones on CT scans within 24 hours before inclusion in observational non-interventional program; Level of consciousness ≤ 5 according to Glasgow Coma Scale and/or ≥ 1 according to Richmond Agitation-Sedation Scale (RASS); Behavioral Pain Scale (BPS) or Visual Analogue Scale assessment score of more than > 0 at the moment of inclusion; Systolic blood pressure < 90 and > 180 mm Hg; Diastolic blood pressure ≥ 110 mm Hg; Mean ABP < 60 mm Hg; Clinical and/or electrocardiographic signs of acute coronary syndrome (including de novo ST elevation or depression, negative T-waves amplitude formation and buildup, formation of pathological Q-wave, increase in the level of markers of myocardial injury - troponin T or I, creatine phosphokinase-MB, LDH-1), or diagnosed acute myocardial infarction occurring within a month before inclusion in observational program; Acute heart arrhythmias; Heart rate (HR) < 60 or > 100 per minute; Spontaneous respiration rate (RR) < 10 or > 30 per minute; Arterial oxygen saturation (SpO2) < 90 %; Venous serum glucose level ≤ 4 mmol/L; Axillary body temperature ≥ 38.5 °C; Hematocrit ≤ 30 %; Level of hemoglobin ≤ 80 g/l; Serum total protein ≤ 55 g/l; Positive passive leg raising test (PRL-test); Acute heart failure; Acute respiratory failure; Acute kidney injury; Acute liver cell failure; Congestive heart failure; Chronic respiratory failure, stage greater than I; Chronic kidney disease with estimated glomerular filtration rate using Cockcroft-Gault formula < 60 ml/min/1.73 m2; Clinically significant deviations in the results of complete blood count, blood chemistry, common urine analysis, except those that are acceptable according to other non inclusion criteria; Purulent-inflammatory diseases at any location; Refuse of the patient to undergo verticalization or exercise sessions; Use of medicinal products belonging to the pharmaceutical therapeutic category of metabolic drugs at the time of inclusion in observational non-interventional program, as well as plans for their use during study; Plans for use of physical rehabilitation methods other than verticalization and cycling exercise sessions during the course of the program.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Patients that receive Cytoflavin® medication i/v drop infusion at a dose of 10 ml of solution for injection per 200 ml of 0.9 % sodium chloride solution for 10 days in addition to a set of neurorehabilitation activities | |
| Group 2<br>Patients that subjected to the standard set of neurorehabilitation activities for 10 days without being prescribed Cytoflavin® medication | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median time to achieving gravity gradient of 90° | Median time (in days) to achieving gravity gradient of 90°. | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieved gravity gradient of 90° | Proportion of patients who achieved gravity gradient of 90° by day 5 and 10 days of rehabilitation activities | 5 and 10 days | 
| Change in of oxygen consumption during 90° verticalization | Change in of oxygen consumption during 90° verticalization | 5 and 10 days | 
| Change in the Medical Research Council (MRC) scale for muscle strength score | Medical Research Council scale for muscle power (MRC), where 0 - tetraplegia, 60 - normal value | 5 and 10 days | 
| Change in Barthel index (BI) | Barthel index (BI), when 0 - complete inability to self-service, 100 - full capability of self-service | 5 and 10 days of rehabilitation activities | 
| Change in Modified Rankin scale (MRS) score | Modified Rankin scale (MRS), when 0 - no disability, 5 - severe disability | 5 and 10 days of rehabilitation activities | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ischemic stroke, Post-intensive care syndrome, Cytoflavin, Rehabilitation, Metabolograph, Utilization O2, Verticalization