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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 13
- 主要终点
- Montreal Cognitive Assessment (MoCA) scale score
研究概览
简要总结
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.
详细描述
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:
- To study the efficacy of Cytoflavin® administered in elderly patients age for the prevention of cognitive decline after major surgery.
- To study the safety and tolerability of Cytoflavin® in elderly patients for after major surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
- •Course intake of nootropic drugs in the previous 3 months
- •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.
- •The presence in the history of any significant, according to the physician-researcher, condition that prevents the inclusion of the patient in the study.
- •Participation in any clinical study in the previous 3 months
- •Employees of the study centres and their family members.
研究组 & 干预措施
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).
干预措施: Cytoflavin® solution (Drug)
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).
干预措施: Cytoflavin® enteric-coated tablet (Drug)
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).
干预措施: Placebo solution (Drug)
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).
干预措施: Placebo enteric-coated tablet (Drug)
结局指标
主要结局
Montreal Cognitive Assessment (MoCA) scale score
时间窗: 32 days
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.
次要结局
- Montreal Cognitive Assessment (MoCA) follow-up(90 days)
- Anxiety/depression(day 32, day 90)
- Proportion of postoperative delirium(day 3-6)
- The Mini-Mental State Examination (MMSE) scale(32 days)
- The Mini-Mental State Examination (MMSE) follow-up score(90 days)
- Median Montreal Cognitive Assessment (MoCA) scale score(day 7, 32, 90)
- Length of stay in the ICU(day 32)
- Mortality(day 32)
- Quality of life score(day 90)
- Median group Mini-Mental State Examination (MMSE) score(day 7, 32, 90)
- Postoperative cognitive decline(day 32, day 90)
- Independence and activity(day 32)