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Cognitive DysfunctionPhase 3NCT03849664

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

A Phase 3 study testing Cytoflavin® solution and Cytoflavin® enteric-coated tablet in people with Cognitive Dysfunction, run by POLYSAN Scientific & Technological Pharmaceutical Company at 13 sites in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Ages 60 to 80 years
Conditions the study is for
Cognitive Dysfunction
What is being tested?
Cytoflavin® solution and Cytoflavin® enteric-coated tablet
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
200 participants
Where
13 sitesRussia
Study dates
2 Jun 2017to 11 Jul 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Russia13 sites

  • Regional Clinical Hospital № 3

    Chelyabinsk

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

    Moscow

  • Alexandrovskaya City Hospital

    Saint Petersburg

  • City Hospital №15

    Saint Petersburg

  • City Hospital №38 named after N.A. Semashko

    Saint Petersburg

  • City Hospital №40 of the Kurortny District

    Saint Petersburg

  • Hospital for War Veterans

    Saint Petersburg

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

    Saint Petersburg

  • Military Medical Academy named after S.M. Kirov

    Saint Petersburg

  • Pokrovskaya City Hospital

    Saint Petersburg

  • GBUZ YAO "Regional Clinical Hospital"

    Yaroslavl

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

    Yekaterinburg

  • Ural State Medical University

    Yekaterinburg

Other trials in Russia

About this study

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

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.

Read the 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.
Being tested
Cytoflavin® solution, Cytoflavin® enteric-coated tablet, Placebo solution, Placebo enteric-coated tablet
Keywords
postoperative cognitive decline
Medical subject headings
Cognitive Dysfunction, Postoperative Cognitive Complications

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cytoflavin® solutionDrug

    Also called Inosine + Nicotinamide + Riboflavin + Succinic Acid solution

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

  • Cytoflavin® enteric-coated tabletDrug

    Also called Inosine+Nicotinamide+Riboflavin+Succinic Acid 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 solutionDrug

    Also called riboflavin; meglumine, soduim hydroxide, water

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

  • Placebo enteric-coated tabletDrug

    Also called povidone, calcium stearate, hypromellose, polysorban, dyes

    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).

Study groups in NCT03849664
Study groupRoleWhat they receive
Cytoflavin®ExperimentalPatients 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).
Receives: Drug: Cytoflavin® solution; Drug: Cytoflavin® enteric-coated tablet
PlaceboPlacebo comparatorPatients 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).
Receives: Drug: Placebo solution; Drug: Placebo enteric-coated tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 32 days

Secondary outcomes (12)

  1. 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

    Measured: 32 days

  2. 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

    Measured: 90 days

  3. 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

    Measured: 90 days

  4. 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.

    Measured: day 7, 32, 90

  5. 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

    Measured: day 7, 32, 90

  6. 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

    Measured: day 3-6

  7. Length of stay in the ICU

    Length of stay in the ICU

    Measured: day 32

  8. Mortality

    Mortality in the postoperative period in the experimental and control groups

    Measured: day 32

  9. 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

    Measured: day 32, day 90

  10. Quality of life score

    Change in the overall score for the EQ-5D questionnaire for assessing the quality of life

    Measured: day 90

  11. 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

    Measured: day 32

  12. 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).

    Measured: day 32, day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2019
  2. Study start2 Jun 2017
  3. Primary completion11 Apr 2019
  4. Study completion11 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03849664
Sponsor's protocol ID
CYT-COG-16
Status last verified
Jan 2023
First submitted
20 Feb 2019
Last updated
31 Jan 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cytoflavin® solution and Cytoflavin® enteric-coated tablet in people with Cognitive Dysfunction, run by POLYSAN Scientific & Technological Pharmaceutical Company at 13 sites in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montreal Cognitive Assessment (MoCA) scale score (time frame: 32 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03849664, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2023.

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