E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-severe traumatic brain injury |
Traumatism cerebral moderat-sever |
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E.1.1.1 | Medical condition in easily understood language |
Brain injury |
Traumatism cerebral |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 26.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060690 |
E.1.2 | Term | Traumatic brain injury |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess GOSE outcomes at 90 days after baseline |
Evaluarea rezultatelor pe scala Glasgow Outcome Scale Extended (GOSE) la 90 de zile de la debut. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of Cerebrolysin versus Placebo upon neurological deficit, functional outcome, symptoms of anxiety and depression, drug safety and quality of life 30, 90 and 180 days after baseline |
Evaluarea eficacității Cerebrolysin versus Placebo asupra deficitului neurologic, rezultatelor funcționale, simptomelor de anxietate și depresie, siguranței tratamentului și asupra calității vieții la 30, 90 și 180 de zile după inițiere. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Diagnosis of TBI and a GCS score of 7-12 (best available score in 24h after hospital admission). Pre-hospital intubation/sedation/paralysis is accepted if the GCS score has been assessed before intubation/sedation/paralyses by trained personnel. ● Pre-treatment GCS score of 7-12. If intubation/sedation/paralysis occurs after hospital admission, the pre-treatment GCS score has been assessed before intubation/sedation/paralyses. ● Isolated TBI only (abbreviated injury score (AIS) in other body regions of ≤2) ● CT (Marshal classification) I to VI (from diffuse injury to non-evacuated mass lesion) ● Pre-Trauma Karnofsky Index = 100. If no corresponding information is available before the start of treatment (e.g., patient is unconscious or not able to communicate) and no information is retrieved within 24 hours after the start of treatment, the patient stays in the study. If no information is available before the start of treatment and a violation of the Karnofsky Index is detected within 24 hours after the start of treatment, the patient is withdrawn from the study, and the treatment medication is stopped. ● Aged 18-85 years ● Able to provide written informed consent to enrollment ● Willing and able to comply with the protocol requirements for the duration of the study ● Women of child-bearing potential with a negative urine pregnancy test who are willing to practice an acceptable method of birth control ● Time to needle for study medication should be within 12 hours ● Patients were able to speak, read and write before the accident. If no corresponding information is available before the start of treatment (e.g., patient is unconscious or not able to communicate) and if no information is retrieved within 24 hours after the start of treatment, the patient should remain in the study. If no information is available before the start of treatment and if a violation of this inclusion criterion is detected within 24 hours after the start of treatment, the patient should be withdrawn from the study, and the treatment medication should be stopped.
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● Diagnostic de traumatism cerebral și scor GCS de 7-12 (cel mai bun scor disponibil la 24 de ore după internare). Intubarea/sedarea/paralizia pre-spital este acceptată dacă scorul GCS a fost calculat de personal calificat înainte de intubare/sedare/paralizie. ● Scor GCS 7-12 pre-tratament. Dacă intubarea/sedarea/paralizia survine după internare, scorul GCS pre-tratament a fost calculat înainte de intubare/sedare/paralizie. ● Traumatism cerebral izolat (scor AIS ≤2 în celelalte părți ale corpului). ● Clasificare Marshall a computerului tomograf de la I la VI (de la injurie difuză la leziune de masă neevacuată). ● Index Karnofsky înainte de traumă = 100. Dacă aceste informații nu pot fi obținute înainte de începerea tratamentului (e.g., pacientul este inconștient sau nu este capabil de a comunica) și nu sunt obținute în 24 de ore de la începerea tratamentului, pacientul rămâne în studiu. Dacă aceste informații nu sunt obținute înainte de începerea tratamentului și este detectată o încălcare a acestui criteriu de includere în 24 de ore de la începerea tratamentului, pacientul este retras din studiu, iar tratamentul este oprit. ● Vârsta de 18-85 ani. ● Pacient capabil de a-și oferi consimțământul informat scris pentru înrolare. ● Pacient care dorește și este capabil să se conformeze cerințelor protocolului pe durata studiului. ● Femei care au potențialul de a rămâne însărcinate, care au test urinar de sarcină negativ și care doresc să utilizeze metode contraceptive potrivite. ● Durata “time to needle” pentru medicamentul studiat ar trebui să fie până la 12 ore. ● Pacient capabil să vorbească, să citească și să scrie înainte de traumatism. Dacă aceste informații nu pot fi obținute înainte de începerea tratamentului (e.g., pacientul este inconștient sau nu este capabil de a comunica) și nu sunt obținute în 24 de ore de la începerea tratamentului, pacientul rămâne în studiu. Dacă aceste informații nu sunt obținute înainte de începerea tratamentului și este detectată o încălcare a acestui criteriu de includere în 24 de ore de la începerea tratamentului, pacientul este retras din studiu, iar tratamentul este oprit.
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E.4 | Principal exclusion criteria |
● Patients with polytrauma (AIS score in other body regions of >2) ● Patients with spinal cord injury ● History of intracranial intervention or ischemic or hemorrhagic stroke ● Existence of psychiatric disorders or neurodegenerative diseases ● Patients who in the investigator’s opinion would not comply with study procedures ● Patients with a history of epileptic seizure ● Use of concomitant neuroprotective treatment or cholinesterase inhibitors for previous cognitive treatment ● Persons who are under chronic treatment with cortisone, Ca+-channel blockers, antidepressants (unstable treatment), antipsychotic drugs or nootropic molecules ● Significant or unstable medical, systemic or logistical condition that affects the subject’s ability to give informed consent or to complete the study procedures
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● Pacient cu politraumatisme (scor AIS >2 în alte părți ale corpului). ● Pacient cu leziuni ale măduvei spinării. ● Istoric de intervenție chirurgicală intracraniană sau accident vascular cerebral hemoragic. ● Pacient care a suferit un accident vascular cerebral ischemic în cele 12 luni dinaintea traumatismului cerebral. ● Existența unor boli neurodegenerative. ● Pacient care, în opinia Investigatorului, nu s-ar conforma procedurilor studiului. ● Pacient cu istoric de crize epileptice. ● Utilizarea concomitentă de tratament neuroprotectiv sau a inhibitorilor de colinesterază pentru tratament cognitiv precedent. ● Pacient aflat sub tratament cronic (>6 luni) cu cortizon, blocanți ai canalelor de calciu, antidepresive (tratament instabil), antipsihotice sau molecule nootrope. ● Afecțiune medicală semnificativă, instabilă sau sistemică, care afectează capacitatea subiectului de a-și oferi consimțământul informat sau de a se conforma procedurilor studiului.
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E.5 End points |
E.5.1 | Primary end point(s) |
The following psychometric tests are included in the primary multivariate analysis (combined cognitive outcome measures): Glasgow Outcome Scale Extended (GOSE)
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Următoarele teste psihometrice sunt incluse în analiza multivariată primară (măsurători cognitive combinate): Glasgow Outcome Scale Extended (GOSE)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days after baseline |
90 zile de la baseline |
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E.5.2 | Secondary end point(s) |
Secondary Variables Early Rehabilitation Barthel Index (ERBI) Mini-Mental State Examination (MMSE) Stroop Color-Word Test – Victoria Version (SCW) Hospital Anxiety and Depression Scale (HADS) Processing Speed Index (PSI) Color Trails Test (CTT) Digit Span Forward and Backward (DS) EQ-5D-5L Patient pathway and cost questionnaire Safety Variables: Deaths Adverse Events (AE) Severe Adverse Events (SAE) Non-Fatal Serious Adverse Events (NF-SAE)
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Variabile secundare Early Rehabilitation Barthel Index (ERBI) Mini-Mental State Examination (MMSE) Stroop Color-Word Test – Victoria Version (SCW) Hospital Anxiety and Depression Scale (HADS) Processing Speed Index (PSI) Color Trails Test (CTT) Digit Span Forward and Backward (DS) EQ-5D-5L Chestionar pentru traseul pacientului și costuri Variabile legate de siguranță: Decese Evenimente adverse (AE) Evenimente adverse severe (SAE) Evenimente adverse severe nefatale (NF-SAE)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
30,90 and 180 days after baseline |
30,90 si 180 zile de la baseline |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject undergoing the trial. |
Ultima vizita a ultimului pacient efectuata in studiu clinic |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |