International Trial of Efficacy of Cytoflavin in Head Trauma

NCT04631484 | Completed Phase 3 DMC

• 1 other identifier: CTF-III-CCT-2019
• Study Type: interventional
• Target: 166
• Locations: 2 countries
• Sites: 8

Brief Summary

The study will access the efficacy and safety of treatment with CITOFLAVIN® in patients with non-penetrating moderately severe traumatic brain injury (TBI). The study recruits patients 18-60 years with TBI, corresponding to the clinical diagnosis of brain contusion, with GCS score 9 -14 at the time of inclusion , with the estimated time of initiation of therapy within 24 hours from the estimated or established time of trauma, with post-traumatic amnesia, confusion or disorientation and absence of indications for neurosurgery or other surgical intervention under general anesthesia. Cytoflavin® (Inosine + Nicotinamide + Riboflavin + Succinic Acid) is a combination drug, which improves 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.

Conditions

Head Trauma,Closed

Keywords

closed head injury; brain concussion; traumatic brain injury; TBI; Craniocerebral Trauma; posttraumatic amnesia

Outcome Measures

Primary Outcomes (2)

• Galveston Orientation and Amnesia scale

  The proportion of patients with regression of post-traumatic amnesia by day 7 of treatment, defined as having a Galveston score of \>75 points on 3 consecutive days, up to and including day 7 of treatment.

  7 days

• Glasgow Outcome scale - Extended (GOS-E)

  Assessment by GOS-E after 3 months

  90 days

Secondary Outcomes (2)

• Glasgow Coma Scale

  14 days

• Barthel Index

  14 days

Study Arms (2)

Cytoflavin ((Inosine + Nicotinamide + Riboflavin + Succinic Acid)

EXPERIMENTAL

Patients will receive treatment with the study drug, 20 ml twice a day IV, dissolved in 200 ml of 0.9% NS, for 10 days;patients will stay in the hospital for the the entire period of therapy. Observation of patients and assessment of the main parameters of the efficacy and safety will continue for 14 days.

Drug: Cytoflavin ((Inosine + Nicotinamide + Riboflavin + Succinic Acid)

Placebo

PLACEBO COMPARATOR

Patients will receive 20 ml placebo (0.9% sodium chloride solution) twice a day IV, dissolved in 200 ml of 0.9% NS, for 10 days; patients will stay in the hospital for the the entire period of therapy. Observation of patients and assessment of the main parameters of the efficacy and safety will continue for 14 days.

Drug: Placebo

Interventions

Cytoflavin ((Inosine + Nicotinamide + Riboflavin + Succinic Acid) DRUG

20 ml (2 ampoules, 10 ml each) dissolved in 200 ml of 0.9% sodium chloride, intravenously 2 times a day with an interval of 12 ± 2 hours, for 10 days.

Cytoflavin ((Inosine + Nicotinamide + Riboflavin + Succinic Acid)

Placebo DRUG

20 ml of 0.9% sodium chloride (2 ampoules of 10 ml each), added to 200 ml of 0.9% sodium chloride, intravenously 2 times a day with an interval of 12 ± 2 hours, for 10 days

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age from 18-60 (inclusive).
• Clinical diagnosis of TBI, cerebral contusion of moderate severity without compression.
• The written consent of the legal representative or the decision of the council to include the patient in the study.
• Possibility of a full assessment of eye opening, speech and motor response by GCS.
• Time of initiation of study drug therapy within 24 hours after the estimated or determined time of injury.
• The presence of post-traumatic amnesia, confusion and disorientation.
• Absence of indications for neurosurgery or other surgical intervention under general anesthesia.
• Normal brain CT scan, or the presence of subarachnoid hemorrhage and / or contusion foci of I-III types according to Kornienko and / or limited or diffuse cerebral edema.
• The expected duration of hospital stay \>= 10 days.
• Absence of a disabling neurological or mental illness, information about the patient's disability prior to injury.
• Possibility to perform all procedures stipulated by the study protocol

You may not qualify if:

• The need to use the therapy prohibited by the study protocol.
• Concomitant injury, except for cases of damage to the skeleton, soft tissues, internal organs, which do not require (1) surgical intervention under general anesthesia, and (2) are not an independent indication for hospital treatment.
• Past / planned surgical intervention for the current episode of trauma under general anesthesia.
• Penetrating open TBI.
• Presence of the following lesions on the results of computed tomography (CT) of the brain performed prior to the patient's randomization:
• epidural hematoma or subdural hematoma;
• evidence of a previous head injury based on CT results;
• type IV contusion foci according to Kornienko's classification.
• Presence of any of the following risk factors for secondary brain injury at any time after TBI: hypoxia (SpO2 \<90% based on pulse oximetry results); hypotension (systolic blood pressure \<90 mm Hg) or shock;hypothermia (body temperature \<35 ° C); clinical signs of respiratory failure, the need for mechanical ventilation.
• Drug addiction.
• Alcohol in saliva \>=2 ‰ or a previous diagnosis of alcohol dependence.
• Depression of consciousness, presumably resulting from other reasons (for example, alcohol, drugs, drugs, poisonous substances).
• The presence of aphasia due to focal brain damage, which prevents communication with the researcher.
• Status epilepticus at the time of admission to the hospital or condition after an epileptic seizure.
• Pregnant and lactating women.

Sponsors & Collaborators

• POLYSAN Scientific & Technological Pharmaceutical Company: lead

Study Sites (8)

West Kazakhstan Medical University named after. M. Ospanov

Aktobe, 030012, Kazakhstan

Location

Ivanovskaya Regional Clinical Hospital

Ivanovo, Russia

Location

City Clinical Hospital No. 67 named after L.A. Vorokhobov

Moscow, Russia

Location

Research Institute of Emergency Medicine n.a. N.V. Sklifosovsky

Moscow, Russia

Location

Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko

Nizhny Novgorod, Russia

Location

City Hospital of the Holy Martyr Elizabeth

Saint Petersburg, 197706, Russia

Location

Stavropol Regional Clinical Hospital

Stavropol, Russia

Location

State Autonomous Healthcare Institution of the Sverdlovsk Region "Central City Clinical Hospital No. 23"

Yekaterinburg, Russia

Location

Related Publications (1)

• Kharitonova T, Bragina T, Ivanova E, Savello A, Skoromets T, Petrikov S. A multicenter, international, randomized, single-blind, placebo-controlled study of the efficacy and safety of inosine-nicotinamide-riboflavin-succinic acid in the acute period of traumatic brain injury in adults. Front Neurol. 2026 Jan 2;16:1683976. doi: 10.3389/fneur.2025.1683976. eCollection 2025.

  PMID: 41551305 DERIVED

MeSH Terms

Conditions

Head Injuries, Closed; Brain Concussion; Brain Injuries, Traumatic; Craniocerebral Trauma

Interventions

cytoflavin; Inosine; Niacinamide; Riboflavin; Succinic Acid

Condition Hierarchy (Ancestors)

Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Injuries; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Flavins; Pteridines; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors; Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Alexander V Savello, Prof

  S. M. Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation

  STUDY DIRECTOR

• Taras A Skoromets, Prof

  National Medical Research Center of Psychiatry and Neurology named after V.M. Bekhterev

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participant, Outcomes Assessor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: International, multicenter, randomized, single blind, third party (outcome assessor) blinding

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 17, 2020
• Study Start: November 22, 2020
• Primary Completion: May 7, 2024
• Study Completion: September 24, 2024
• Last Updated: April 18, 2025

Record last verified: 2025-04

Locations

KA (1); RU (7)