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

Cognitive Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03849664
• Other study ID #: CYT-COG-16
• Status: Completed
• Phase: Phase 3
• Start date: June 2, 2017
• Est. completion date: July 11, 2019

Study information

• Verified date: January 2023
• Source: POLYSAN Scientific & Technological Pharmaceutical Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: July 11, 2019
• Est. primary completion date: April 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction

Intervention

Drug:
• Cytoflavin® solution
Single drip infusion of 20 ml of Cytoflavin® solution in 200 ml of 0.9%NaCl intravenously once a day
• 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).
• Placebo solution
Single drip infusion of 20 ml of placebo solution in 200 ml of 0.9%NaCl intravenously once a day
• 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).

Locations

Country	Name	City	State
Russian Federation	Regional Clinical Hospital ? 3	Chelyabinsk
Russian Federation	Central Clinical Hospital with a polyclinic of the Office of the President of the Russian Federation	Moscow
Russian Federation	Alexandrovskaya City Hospital	Saint Petersburg
Russian Federation	City Hospital ?15	Saint Petersburg
Russian Federation	City Hospital ?38 named after N.A. Semashko	Saint Petersburg
Russian Federation	City Hospital ?40 of the Kurortny District	Saint Petersburg
Russian Federation	Hospital for War Veterans	Saint Petersburg
Russian Federation	I. P. Pavlov 1st St. Petersburg State Medical University	Saint Petersburg
Russian Federation	Military Medical Academy named after S.M. Kirov	Saint Petersburg
Russian Federation	Pokrovskaya City Hospital	Saint Petersburg
Russian Federation	GBUZ YAO "Regional Clinical Hospital"	Yaroslavl
Russian Federation	Research center of specialized types of medical care "Ural Institute of Cardiology"	Yekaterinburg
Russian Federation	Ural State Medical University	Yekaterinburg

Sponsors (1)

Lead Sponsor	Collaborator
POLYSAN Scientific & Technological Pharmaceutical Company

Country where clinical trial is conducted

Russian Federation, 

References & 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The Mini-Mental State Examination (MMSE) scale	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	32 days
Secondary	The Mini-Mental State Examination (MMSE) follow-up score	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	90 days
Secondary	Montreal Cognitive Assessment (MoCA) follow-up	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	90 days
Secondary	Median group Mini-Mental State Examination (MMSE) score	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.	day 7, 32, 90
Secondary	Median 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 difference in median group values of the MOCA scale	day 7, 32, 90
Secondary	Proportion of postoperative delirium	The proportion of patients who developed postoperative delirium in the first 96 hours after surgery according to the results of CAM-ICU	day 3-6
Secondary	Length of stay in the ICU	Length of stay in the ICU	day 32
Secondary	Mortality	Mortality in the postoperative period in the experimental and control groups	day 32
Secondary	Postoperative cognitive decline	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	day 32, day 90
Secondary	Quality of life score	Change in the overall score for the EQ-5D questionnaire for assessing the quality of life	day 90
Secondary	Independence and activity	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	day 32
Secondary	Anxiety/depression	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).	day 32, day 90

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