- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03849664
Efficacy and Safety of Cytoflavin® Used in Elderly Patients for the Prevention of Cognitive Decline After Major Surgery
A Multicentre Double-blind Placebo-controlled Randomized Study of Efficacy and Safety of Cytoflavin®, Intravenous Administration and Enteric-coated Tablets, Used in Elderly Patients for Prevention of Cognitive Decline After Major Surgery
Study Overview
Status
Conditions
Detailed Description
Cytoflavin® (Inosine + Nicotinamide + Riboflavin + Succinic Acid) is a combination drug, which improves coronary and cerebral blood flow, activates metabolic processes in the central nervous system, restores impaired consciousness, promotes regression of neurological symptoms and improvement of cognitive functions of the brain. It has a quick awakening effect in post-anesthetic depression of consciousness. The positive effect of Cytoflavin® on cognitive function has been previously shown in patients with dyscirculatory encephalopathy and acute stroke, as well as in a population of patients during cardiac surgery in cardiopulmonary bypass and working heart. The present study aims to evaluate the opportunity of prevention of postoperative cognitive decline by administration of Cytoflavin® at a sequential regimen, starting from intravenous infusions and followed by oral intake during 1 month.
Study objectives:
- To study the efficacy of Cytoflavin® administered in elderly patients age for the prevention of cognitive decline after major surgery.
- To study the safety and tolerability of Cytoflavin® in elderly patients for after major surgery.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Chelyabinsk, Russian Federation
- Regional Clinical Hospital № 3
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Moscow, Russian Federation
- Central Clinical Hospital with a polyclinic of the Office of the President of the Russian Federation
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Saint Petersburg, Russian Federation
- Pokrovskaya City Hospital
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Saint Petersburg, Russian Federation
- Alexandrovskaya City Hospital
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Saint Petersburg, Russian Federation
- City Hospital №15
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Saint Petersburg, Russian Federation
- City Hospital №38 named after N.A. Semashko
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Saint Petersburg, Russian Federation
- City Hospital №40 of the Kurortny District
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Saint Petersburg, Russian Federation
- Hospital for War Veterans
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Saint Petersburg, Russian Federation
- I. P. Pavlov 1st St. Petersburg State Medical University
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Saint Petersburg, Russian Federation
- Military Medical Academy named after S.M. Kirov
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Yaroslavl, Russian Federation
- GBUZ YAO "Regional Clinical Hospital"
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Yekaterinburg, Russian Federation
- Research center of specialized types of medical care "Ural Institute of Cardiology"
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Yekaterinburg, Russian Federation
- Ural State Medical University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed informed consent
- Men and women aged 60-80 years, inclusive.
- Planned cardiac surgery, which does not assume the use of a cardiopulmonary bypass.
- Planned or delayed orthopedic surgery (hip joint endoprosthetics, osteosynthesis for fractures of the proximal third of the hip, etc.), under general or combined anesthesia.
- Legal capacity of the patient
- Absence of dementia (MoCA≥17, MMSE≥19)
- Lack of reproductive potential or
- Consent to use adequate methods of contraception
Exclusion Criteria:
- Hypersensitivity to any component of the study drug
- Emergency surgery
- Repeated surgery or reoperation
- Anesthesia risk ASA≥5
- Severe visual or hearing impairment which impedes the performance of neuropsychological tests
- Operation under general anesthesia in the previous 3 months
- Severe renal failure requiring replacement of renal function (dialysis)
- Severe hepatic failure (class C and above in Child-Pugh)
- Chronic obstructive pulmonary disease
- Terminal stage of other chronic incurable diseases
- Decompensated diabetes
- A history of oncological diseases, mental illness, HIV infection, syphilis, tuberculosis, alcohol or drug addiction
- The use of 5 or more units of alcohol per week in the previous 3 months
- Diagnosis of mental or neurodegenerative disease (e.g. schizophrenia, Parkinson's disease, clinically manifest depression)
- Permanent intake of psychotropic drugs (neuroleptics, tranquilizers, antidepressants)
- Course intake of nootropic drugs in the previous 3 months
- Communicative, sensory, motor, or any other deficiency that does not allow the patient to adequately assess their behavior and correctly fulfill the conditions of the study protocol.
- The presence in the history of any significant, according to the physician-researcher, condition that prevents the inclusion of the patient in the study.
- Participation in any clinical study in the previous 3 months
- Employees of the study centres and their family members.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cytoflavin®
Patients of group I will receive the experimental drug Cytoflavin®, manufactured by POLYSAN (Russia), on the day before surgery, during the surgical intervention, and in the postoperative period.
Cytoflavin® solution(Inosine + Nicotinamide + Riboflavin + Succinic Acid) will be administered IV for 7 days, and Cytoflavin® enteric-coated tablets (Inosine + Nicotinamide + Riboflavin + Succinic Acid) will be administered for 25 days (in total 32 days of treatment).
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Single drip infusion of 20 ml of Cytoflavin® solution in 200 ml of 0.9%NaCl intravenously once a day
Other Names:
2 tablets, orally, with 100 ml of drinking water, 30 minutes before meals, 2 times a day, with an interval of 8-10 hours (but no later than 18:00).
Other Names:
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Placebo Comparator: Placebo
Patients of group II will receive placebo (manufactured by POLYSAN, Russia), on the day before surgery, during the surgical intervention, and in the postoperative period.
Placebo solution will be administered IV for 7 days, and placebo enteric-coated tablets will be administered for 25 days (in total 32 days of treatment).
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Single drip infusion of 20 ml of placebo solution in 200 ml of 0.9%NaCl intravenously once a day
Other Names:
2 tablets, orally, with 100 ml of drinking water, 30 minutes before meals, 2 times a day, with an interval of 8-10 hours (but no later than 18:00).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Montreal Cognitive Assessment (MoCA) scale score
Time Frame: 32 days
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The MoCA test is a one-page 30-point test, ranging between 0 and 30, where 0 is the worst and 30 is the best result; a score of 26-30 or over is considered to be normal.
Outcome measure is the change in the MoCA scale score by the end of the treatment course compared with the preoperative score.
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32 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Mini-Mental State Examination (MMSE) scale
Time Frame: 32 days
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MMSE test is a 30-point questionnaire; any score greater than or equal to 24 points (out of 30) indicates a normal cognition; below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.
Outcome measure will be the change of MMSE scale score by the end of the treatment course compared to the preoperative score
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32 days
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The Mini-Mental State Examination (MMSE) follow-up score
Time Frame: 90 days
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MMSE test is a 30-point questionnaire; any score greater than or equal to 24 points (out of 30) indicates a normal cognition; below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.
Outcome measure will be the change of MMSE scale score by the end of the follow-up period
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90 days
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Montreal Cognitive Assessment (MoCA) follow-up
Time Frame: 90 days
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The MoCA test is a one-page 30-point test, ranging between 0 and 30, where 0 is the worst and 30 is the best result; a score of 26-30 or over is considered to be normal.
Outcome measure is the change of the MoCA scale score by the end of the follow-up period
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90 days
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Median group Mini-Mental State Examination (MMSE) score
Time Frame: day 7, 32, 90
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MMSE test is a 30-point questionnaire; any score greater than or equal to 24 points (out of 30) indicates a normal cognition; below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.
Outcome measure will be the difference between median group total scores on the MMSE scale.
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day 7, 32, 90
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Median Montreal Cognitive Assessment (MoCA) scale score
Time Frame: day 7, 32, 90
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The MoCA test is a one-page 30-point test, ranging between 0 and 30, where 0 is the worst and 30 is the best result; a score of 26-30 or over is considered to be normal.
Outcome measure is the difference in median group values of the MOCA scale
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day 7, 32, 90
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Proportion of postoperative delirium
Time Frame: day 3-6
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The proportion of patients who developed postoperative delirium in the first 96 hours after surgery according to the results of CAM-ICU
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day 3-6
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Length of stay in the ICU
Time Frame: day 32
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Length of stay in the ICU
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day 32
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Mortality
Time Frame: day 32
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Mortality in the postoperative period in the experimental and control groups
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day 32
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Postoperative cognitive decline
Time Frame: day 32, day 90
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The proportion of patients with a decrease in the results of two or more neuropsychological tests by more than 20% by the end of the treatment course and by the end of the follow-up period compared the baseline values
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day 32, day 90
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Quality of life score
Time Frame: day 90
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Change in the overall score for the EQ-5D questionnaire for assessing the quality of life
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day 90
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Independence and activity
Time Frame: day 32
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The proportion of patients dependent in at least two daily functions according to the results of the Katz Daily Activity Index at the end of the treatment course
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day 32
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Anxiety/depression
Time Frame: day 32, day 90
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The group average score by Hospital Anxiety and Depression Scale (HADS) at the end of the treatment course and at the end of the follow-up period.
The HADS is a fourteen item scale, a person can score between 0 and 21 for either anxiety or depression, where scores on each scale can be interpreted in ranges: normal (0-7), mild (8-10), moderate (11-14) and severe (15-21).
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day 32, day 90
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Collaborators and Investigators
Investigators
- Study Director: Tatiana V Kharitonova, MD, PhD, St. Petersburg Research Institute of Emergency Medicine n.a. I.I. Dzhanelidze
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Neurocognitive Disorders
- Cognition Disorders
- Cognitive Dysfunction
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Antimetabolites
- Photosensitizing Agents
- Dermatologic Agents
- Micronutrients
- Hypolipidemic Agents
- Lipid Regulating Agents
- Vitamins
- Vitamin B Complex
- Plasma Substitutes
- Blood Substitutes
- Pharmaceutical Solutions
- Povidone
- Nicotinic Acids
- Riboflavin
- Niacinamide
- Niacin
- Flavin Mononucleotide
Other Study ID Numbers
- CYT-COG-16
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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