Efficacy of Cerebrolysin Treatment as an add-on Therapy to Mechanical Thrombectomy in Acute Ischemic Stroke.

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This study is designed to determine the efficacy and safety of Cerebrolysin treatment as an add- on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). The investigators have planned a single centre, prospective, open-label, single-arm study with 12 months follow-up of 50 patients with moderate to severe AIS, with a small established infarct core and with good collateral circulation who achieve significant reperfusion following MT and who receive additional Cerebrolysin within 8 hours of stroke onset compared to 50 historical controls treated with MT alone - matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion time and use of iv thrombolytic therapy (rt-PA).

The primary outcome measure will be overall proportion of subjects receiving Cerebrolysin comparing to control group experiencing a favorable functional outcome (by modified Rankin Scale [mRS] 0-2) at 7 day, 30 days, 90 days and 12 months following stroke onset. The secondary objectives are to determine the efficacy of Cerebrolysin as compared to control group in reducing risk of symptomatic secondary hemorrhagic transformation, improving neurological outcome (NIHSS 0-2 at day 7, day 30 and 90); reducing mortality rates (over the 90-day and 12 months study period); and improving: activities of daily living (by Barthel Index; BI), health-related quality of life (as measured by the EQ-5D-5L) assessed at day 30, 90 and at 12 months. The other measures of efficacy in Cerebrolysin group will include: assessment of final stroke volume and penumbral salvage (measured by CT/CTP at 30 days) and its change compared to baseline volume, changes over time in language function (by the 15-item Boston Naming Test), hemispatial neglect (by line bisection test), global cognitive function (by The Montreal Cognitive Assessment) and depression (by Hamilton Depression Rating Scale) between day 30 and day 90 assessments). The patients will receive 30 ml of Cerebrolysin within 8h of AIS stroke onset and continue treatment once daily until day 21 (first cycle) and they will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90 (± 3 days). All the patients (including those from the control group) receive the same standardized rehabilitation program (including speech therapy, occupational and physical therapy) during hospitalization at Stroke Unit and at Neurorehabilitation Clinic until day 90 according to local procedures. Historical data will be obtained by retrospective clinical chart reviews of patients hospitalized in the study center between Jan.2018 and Dec.2020 and fulfilling the same clinical and radiological inclusion criteria in whom 12-month follow-up (including mRS, NIHSS, BI, EQ-5D-5L) could be obtained.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Military Institute of Medicine, Poland
• Collaborator: Brainomix Limited
• Treatments: Cerebrolysin

Criteria

Inclusion Criteria:

Clinical Inclusion Criteria:

1. Age 18-80 years

2. Signs and symptoms consistent with the diagnosis of an anterior circulation AIS

3. Stroke onset to groin ≤6h (stroke onset is defined as the time the patient was last known to be at their neurologic baseline (wake-up strokes are eligible if they meet the above time limits).

4. mRS ≤1 prior to qualifying stroke (functionally independent for all ADLs)

5. moderate to severe stroke: NIHSS score of ≥5 with presence of any cortical signs (gaze, visual fields, language, or neglect)

6. Initiation of treatment with Cerebrolysin ≤8h following stroke onset (Cerebrolysin group)

7. Patient has signed the Informed Consent form (Cerebrolysin group)

Neuroimaging Inclusion Criteria:

1. CT ASPECTS ≥6 prior to MT

2. ICA or MCA-M1 or -M2 occlusion (carotid occlusions can be cervical or intracranial; without tandem MCA lesions) by CTA

3. Target mismatch profile on CTP (ischemic core volume <70 ml, mismatch ratio ≥1.8 (ischemic penumbra at least 180% larger than the ischemic core volume) and mismatch volume ≥15 ml)

4. Moderate-to-good collateral status on multiphase CTA (>50% MCA territory)

5. Effective reperfusion mTICI ≥2b following MT

Exclusion Criteria:

Clinical Exclusion Criteria:

1. Other serious, advanced, or terminal illness or life expectancy ≤ 6 months

2. Pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations (e.g. Alzheimer's disease, vascular dementia, Parkinson's disease, demyelinating disease, encephalopathy of any cause,a history of significant alcohol or drugabuse)

3. Pregnancy or lactation

4. Known allergy to iodine that precludes an endovascular procedure

5. Acute or chronic renal failure with calculated creatinine clearance <30 ml/min/1.73m2 or unable to undergo a contrast brain perfusion scan withCT

6. Inability to tolerate or comply with studyprocedures

7. Any condition that would represent a contraindication for Cerebrolysin administration (e.g.allergy)

Neuroimaging Exclusion Criteria:

1. Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)

2. Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation

3. Significant mass effect with midline shift

4. Treatment with another investigational drug within the last 30 days that may interfere with this study's medications

5. Patients with nondiagnostic NCCT or CTP maps