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

NCT ID: NCT03849664

Last Updated: 2023-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-02
• Study Completion Date: 2019-07-11

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.

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:

1. To study the efficacy of Cytoflavin® administered in elderly patients age for the prevention of cognitive decline after major surgery.

2. To study the safety and tolerability of Cytoflavin® in elderly patients for after major surgery.

Conditions

Cognitive Dysfunction

Study Design

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

Study Groups

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).

Group Type: EXPERIMENTAL

Cytoflavin® solution

Intervention Type: DRUG

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

Cytoflavin® enteric-coated tablet

Intervention Type: 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).

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).

Group Type: PLACEBO_COMPARATOR

Placebo solution

Intervention Type: DRUG

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

Placebo enteric-coated tablet

Intervention Type: 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).

Interventions

Cytoflavin® solution

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

Intervention Type: DRUG

Cytoflavin® enteric-coated tablet

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).

Intervention Type: DRUG

Placebo solution

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

Intervention Type: DRUG

Placebo enteric-coated tablet

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).

Intervention Type: DRUG

Other Intervention Names

Inosine + Nicotinamide + Riboflavin + Succinic Acid solution; Inosine+Nicotinamide+Riboflavin+Succinic Acid tablet; riboflavin; meglumine, soduim hydroxide, water; povidone, calcium stearate, hypromellose, polysorban, dyes

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent

2. Men and women aged 60-80 years, inclusive.

3. Planned cardiac surgery, which does not assume the use of a cardiopulmonary bypass.

4. Planned or delayed orthopedic surgery (hip joint endoprosthetics, osteosynthesis for fractures of the proximal third of the hip, etc.), under general or combined anesthesia.

5. Legal capacity of the patient

6. Absence of dementia (MoCA≥17, MMSE≥19)

7. Lack of reproductive potential or

8. Consent to use adequate methods of contraception

Exclusion Criteria

1. Hypersensitivity to any component of the study drug

2. Emergency surgery

3. Repeated surgery or reoperation

4. Anesthesia risk ASA≥5

5. Severe visual or hearing impairment which impedes the performance of neuropsychological tests

6. Operation under general anesthesia in the previous 3 months

7. Severe renal failure requiring replacement of renal function (dialysis)

8. Severe hepatic failure (class C and above in Child-Pugh)

9. Chronic obstructive pulmonary disease

10. Terminal stage of other chronic incurable diseases

11. Decompensated diabetes

12. A history of oncological diseases, mental illness, HIV infection, syphilis, tuberculosis, alcohol or drug addiction

13. The use of 5 or more units of alcohol per week in the previous 3 months

14. Diagnosis of mental or neurodegenerative disease (e.g. schizophrenia, Parkinson's disease, clinically manifest depression)

15. Permanent intake of psychotropic drugs (neuroleptics, tranquilizers, antidepressants)

16. Course intake of nootropic drugs in the previous 3 months

17. 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.

18. The presence in the history of any significant, according to the physician-researcher, condition that prevents the inclusion of the patient in the study.

19. Participation in any clinical study in the previous 3 months

20. Employees of the study centres and their family members.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

POLYSAN Scientific & Technological Pharmaceutical Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tatiana V Kharitonova, MD, PhD

Role: STUDY_DIRECTOR

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

Locations

Regional Clinical Hospital № 3

Chelyabinsk, , Russia

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

Moscow, , Russia

Alexandrovskaya City Hospital

Saint Petersburg, , Russia

City Hospital №15

Saint Petersburg, , Russia

City Hospital №38 named after N.A. Semashko

Saint Petersburg, , Russia

City Hospital №40 of the Kurortny District

Saint Petersburg, , Russia

Hospital for War Veterans

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Military Medical Academy named after S.M. Kirov

Saint Petersburg, , Russia

Pokrovskaya City Hospital

Saint Petersburg, , Russia

GBUZ YAO "Regional Clinical Hospital"

Yaroslavl, , Russia

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

Yekaterinburg, , Russia

Ural State Medical University

Yekaterinburg, , Russia

Countries

Russia

References

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

Reference Type: BACKGROUND

Related Links

https://doi.org/10.15360/1813-9779-2022-2-12-21

Related Info

Other Identifiers

CYT-COG-16

Identifier Type: -

Identifier Source: org_study_id