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

Polysan

Status and phase: Completed; Phase 3

Conditions: Cognitive Dysfunction

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03849664

CYT-COG-16

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: All

Ages: 60 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

200 participants in 2 patient groups, including a placebo group

Cytoflavin®

Experimental group

Description:

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).

Treatment:

Drug: Cytoflavin® solution

Drug: Cytoflavin® enteric-coated tablet

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo enteric-coated tablet

Drug: Placebo solution