Efficacy and Safety of Cytoflavin® Used in Elderly Patients for the Prevention of Cognitive Decline After Major Surgery

NCT03849664 | Completed Phase 3

• 1 other identifier: CYT-COG-16
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 13

Brief Summary

Postoperative cognitive impairment develops in the early and continues in the late postoperative period; it is manifested by impaired memory, attention, concentration and other higher cortical functions (thinking, speech). Early studies demonstrated the positive impact of perioperative administration of Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid), which prevented impairments of intelligence, speech, and attention after cardiac surgery, both in conditions of cardiopulmonary bypass and on a working heart. The aim of the present study is to evaluate the safety and efficacy of Cytoflavin for the prevention of cognitive disorders after major surgeries performed in elderly patients.

Conditions

Cognitive Dysfunction

Keywords

postoperative cognitive decline

Outcome Measures

Primary Outcomes (1)

• Montreal Cognitive Assessment (MoCA) scale score

  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.

  32 days

Secondary Outcomes (12)

• The Mini-Mental State Examination (MMSE) scale

  32 days

• The Mini-Mental State Examination (MMSE) follow-up score

  90 days

• Montreal Cognitive Assessment (MoCA) follow-up

  90 days

• Median group Mini-Mental State Examination (MMSE) score

  day 7, 32, 90

• Median Montreal Cognitive Assessment (MoCA) scale score

  day 7, 32, 90

Study Arms (2)

Cytoflavin®

EXPERIMENTAL

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).

Drug: Cytoflavin® solution; Drug: Cytoflavin® enteric-coated tablet

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo solution; Drug: Placebo enteric-coated tablet

Interventions

Cytoflavin® solution DRUG

Single drip infusion of 20 ml of Cytoflavin® solution in 200 ml of 0.9%NaCl intravenously once a day

Also known as: Inosine + Nicotinamide + Riboflavin + Succinic Acid solution

Cytoflavin®

Cytoflavin® enteric-coated tablet DRUG

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).

Also known as: Inosine+Nicotinamide+Riboflavin+Succinic Acid tablet

Cytoflavin®

Placebo solution DRUG

Single drip infusion of 20 ml of placebo solution in 200 ml of 0.9%NaCl intravenously once a day

Also known as: riboflavin; meglumine, soduim hydroxide, water

Placebo

Placebo enteric-coated tablet DRUG

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).

Also known as: povidone, calcium stearate, hypromellose, polysorban, dyes

Placebo

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• POLYSAN Scientific & Technological Pharmaceutical Company: lead

Study Sites (13)

Regional Clinical Hospital № 3

Chelyabinsk, Russia

Location

Central Clinical Hospital with a polyclinic of the Office of the President of the Russian Federation

Moscow, Russia

Location

Alexandrovskaya City Hospital

Saint Petersburg, Russia

Location

City Hospital №15

Saint Petersburg, Russia

Location

City Hospital №38 named after N.A. Semashko

Saint Petersburg, Russia

Location

City Hospital №40 of the Kurortny District

Saint Petersburg, Russia

Location

Hospital for War Veterans

Saint Petersburg, Russia

Location

I. P. Pavlov 1st St. Petersburg State Medical University

Saint Petersburg, Russia

Location

Military Medical Academy named after S.M. Kirov

Saint Petersburg, Russia

Location

Pokrovskaya City Hospital

Saint Petersburg, Russia

Location

GBUZ YAO "Regional Clinical Hospital"

Yaroslavl, Russia

Location

Research center of specialized types of medical care "Ural Institute of Cardiology"

Yekaterinburg, Russia

Location

Ural State Medical University

Yekaterinburg, Russia

Location

Related Publications (1)

• Kovalenko A.L., Nagibovich O.A., Vishnevsky A.Yu., Belekhov G.A., Gubaidullin R.R., Popov D.V., Agafiina A.S. Use of a Neurometabolism-Targeting Drug in Prevention of Postoperative Cognitive Dysfunction. General Reanimatology. 2022;18(2):12-21. https://doi.org/10.15360/1813-9779-2022-2-12-21

  BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Cognitive Dysfunction; Postoperative Cognitive Complications

Interventions

Inosine; Niacinamide; Riboflavin; Meglumine; Water; Povidone; stearic acid; Hypromellose Derivatives; Coloring Agents

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Flavins; Pteridines; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Hexosamines; Amino Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Polyvinyls; Vinyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Pyrrolidinones; Pyrrolidines; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Cellulose; Glucans; Biopolymers; Polysaccharides; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Tatiana V Kharitonova, MD, PhD

  St. Petersburg Research Institute of Emergency Medicine n.a. I.I. Dzhanelidze

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: February 21, 2019
• Study Start: June 2, 2017
• Primary Completion: April 11, 2019
• Study Completion: July 11, 2019
• Last Updated: January 31, 2023

Record last verified: 2023-01

Locations

RU (13)