Clinical trial NCT03849664: Efficacy and Safety of Cytoflavin® Used in Elderly Patients for the Prevention of Cognitive Decline After Major Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cognitive Dysfunction
Keywords: postoperative cognitive decline
Lead sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2019-02-21
Enrollment: 200
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Montreal Cognitive Assessment (MoCA) scale score
timeFrame: 32 days
Secondary outcomes:
measure: The Mini-Mental State Examination (MMSE) scale
timeFrame: 32 days
measure: The Mini-Mental State Examination (MMSE) follow-up score
timeFrame: 90 days
measure: Montreal Cognitive Assessment (MoCA) follow-up
timeFrame: 90 days
measure: Median group Mini-Mental State Examination (MMSE) score
timeFrame: day 7, 32, 90
measure: Median Montreal Cognitive Assessment (MoCA) scale score
timeFrame: day 7, 32, 90
measure: Proportion of postoperative delirium
timeFrame: day 3-6
measure: Length of stay in the ICU
timeFrame: day 32
measure: Mortality
timeFrame: day 32
measure: Postoperative cognitive decline
timeFrame: day 32, day 90
measure: Quality of life score
timeFrame: day 90
measure: Independence and activity
timeFrame: day 32
measure: Anxiety/depression
timeFrame: day 32, day 90
Other outcomes:
Locations:
city: Chelyabinsk
country: Russian Federation
facility: Regional Clinical Hospital № 3
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital with a polyclinic of the Office of the President of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Alexandrovskaya City Hospital
city: Saint Petersburg
country: Russian Federation
facility: City Hospital №15
city: Saint Petersburg
country: Russian Federation
facility: City Hospital №38 named after N.A. Semashko
city: Saint Petersburg
country: Russian Federation
facility: City Hospital №40 of the Kurortny District
city: Saint Petersburg
country: Russian Federation
facility: Hospital for War Veterans
city: Saint Petersburg
country: Russian Federation
facility: I. P. Pavlov 1st St. Petersburg State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Military Medical Academy named after S.M. Kirov
city: Saint Petersburg
country: Russian Federation
facility: Pokrovskaya City Hospital
city: Yaroslavl
country: Russian Federation
facility: GBUZ YAO "Regional Clinical Hospital"
city: Yekaterinburg
country: Russian Federation
facility: Research center of specialized types of medical care "Ural Institute of Cardiology"
city: Yekaterinburg
country: Russian Federation
facility: Ural State Medical University
Study officials:
affiliation: St. Petersburg Research Institute of Emergency Medicine n.a. I.I. Dzhanelidze
name: Tatiana V Kharitonova, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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