Exploring Cerebrolysin in Late Thrombectomy for Stroke: Blood-brain Barrier Biomarkers and Imaging Insights

Official title

Examining the Efficacy of Cerebrolysin-Augmented Extended Time Window Thrombectomy in Acute Ischemic Stroke: An In-depth Study of Blood-brain Barrier Biomarkers and Imaging Indicators

Overview

Background: Stroke is a leading cause of mortality and disability globally, with acute ischemic strokes(AIS) due to Large Vessel Occlusion (LVO) presenting significant treatment challenges. Mechanical thrombectomy (MT) has emerged as an effective intervention for AIS within an 8-hour window from symptom onset. However, the potential to extend this window up to 24 hours for select patients could revolutionize outcomes for those arriving late at comprehensive stroke centers. This study investigates the efficacy and safety of Cerebrolysin as an adjunct therapy to MT in extended time window and improving patient recovery. Methods: We conducted a multi-center, prospective, randomized study within the Chang Gung Memorial Hospital system in Taiwan, targeting 100 AIS patients eligible for MT beyond the traditional 8-hour window. Participants were randomized to receive either standard care or Cerebrolysin post-MT, initiated within 24 hours of stroke onset and continued for 14 days. The study assessed neurological, neuropsychological, and biomarker outcomes at multiple time points post-stroke to evaluate the effects of Cerebrolysin on recovery. Results: The primary outcome will measure the proportion of patients achieving favorable functional outcomes (modified Rankin Scale 0-2) at 90 days. Secondary outcomes include the impact of Cerebrolysin on secondary hemorrhagic transformation, brain edema, mortality rates, and quality of life. The study aims to provide comprehensive data on the benefits of adding Cerebrolysin to the standard post-MT care, focusing on its potential to protect against reperfusion injuries and maintain blood-brain barrier integrity. Conclusion: By evaluating the role of Cerebrolysin in conjunction with MT, this study aims to extend the therapeutic window for AIS treatment, offering hope for improved outcomes for patients who would otherwise be ineligible for current reperfusion therapies. The findings may pave the way for new guidelines in stroke management, emphasizing the importance of integrated care approaches in enhancing patient recovery.

Interventions

• Drug Cerebrolysin
  Cerebrolysin post-mechanical thrombectomy, initiated within 24 hours of stroke onset and continued for 14 days. The study assessed neurological, neuropsychological, and biomarker outcomes at multiple time points post-stroke to evaluate the effects of Cerebrolysin on recovery.

Primary outcome measures

• Functional Recovery and Complication Rates Post-Thrombectomy [Time frame: mRS at 90 days and 12 months; NIHSS at 0, 1, and 7 days; mortality and Barthel Index at 90 days and 12 months post-stroke.]

Secondary outcome measures (1)

• Imaging and High cortical Functional Assessment Endpoints [Time frame: Imaging endpoints will be quantified at 30 days (1 month) and at 90 days (3 months) post-stroke. For functional and mood assessments within the Cerebrolysin group, evaluations will be precisely scheduled at 30 days post-stroke to establish early recovery]

Eligibility criteria

Inclusion criteria

• Patients capable of initiating endovascular therapy between 8-24 hours after the time they were last known to be well.
• Age above 18 years.
• NIHSS (National Institutes of Health Stroke Scale) score of ≥6, indicating moderate to severe stroke.
• Presence of likely salvageable ischemic brain tissue, as determined by CT (Computed Tomography) with ASPECTs (Alberta Stroke Program Early CT Score) ≥3.
• Occlusion of the proximal MCA-M1 (middle cerebral artery - M1 segment) or ICA (internal carotid artery) detected on CT angiography.
• Infarct volume <70 ml on Perfusion CT.
• Ischemic tissue showing an infarct volume ratio ≥1.8 on Perfusion CT.
• Absolute volume of potentially reversible ischemia (penumbra) ≥15 ml.
• Minimal pre-existing disability, with a Modified Rankin Scale (mRS) score of 0-2

Exclusion criteria

• Pregnancy
• Pre-existing terminal or debilitating illness
• Seizure activity preventing accurate determination of NIHSS score
• Abnormal blood glucose levels, with values below 50mg/dl or above 400mg/dl
• Platelet count <50,000 or International Normalized Ratio (INR) >3, indicating abnormal blood clotting parameters
• Neuroimaging findings indicating unsuitability for the procedure, such as ASPECTS score <3 on non-contrast CT, presence of intracranial tumor, acute intracranial hemorrhage, or occlusions in multiple vascular territories.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06339411 · 202302239A3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗