Clinical trial NCT06489925: Cerebrolysin as an Add-On Therapy to Standard Treatment of Basilar Artery Occlusion
Official title: Cerebrolysin as an Add-On Therapy to Standard Treatment of Posterior Circulation Stroke Secondary to Basilar Artery Occlusion
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Basilar Artery Occlusion
Posterior Circulation Brain Infarction
Keywords: Cerebrolysin
neuroprotection
basilar artery occlusion
add-on therapy
posterior circulation stroke
Lead sponsor: University Hospital Sestre Milosrdnice
Sponsor class: OTHER
Collaborators: name: Ever Neuro Pharma GmbH
First posted: 2024-07-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The standard therapy for acute ischemic posterior circulation stroke (PCS) often leads to poor functional outcomes and high mortality rates, despite all advances in reperfusion therapy. Recent trials have shown that adding Cerebrolysin, a cerebral neuroprotective agent, to standard therapy for patients with acute ischemic anterior circulation stroke is safe and leads to improved functional outcomes. The purpose of this study is to assess the effectiveness and safety of Cerebrolysin with standard treatment for patients with PCS secondary to basilar artery occlusion (BAO).

The plan is to conduct a prospective, single-center, single-arm, open-label study with 20 acute basilar artery occlusion patients and premorbid modified Rankin Score (mRS) ≤3, treated with standard treatment (mechanical thrombectomy ± intravenous alteplase or conservative treatment) and Cerebrolysin as add-on therapy, compared with historical controls. Besides standard acute stroke assessment, standard treatment, and rehabilitation, the participants who meet the eligibility criteria will receive Cerebrolysin in a single-day dosage of 30 ml intravenously for 14 consecutive days. The participants will be closely monitored, and neuroimaging findings and clinical outcomes will be obtained during the drug administration period, on discharge, one month, and 3 months after the treatment onset.

The primary endpoints are mRS (0-3) on day 90 and mortality rate 90 days after the stroke onset. The secondary endpoints are defined as a change in any type of intracerebral bleeding and a change of min. 2 points on the National Institutes of Health Stroke Scale 24 hours, 14 days, 30 days, and 90 days post-stroke.

The investigators hypothesize that adding Cerebrolysin to standard stroke treatment will improve clinical outcomes and reduce morbidity and mortality in patients with acute basilar occlusion compared to standard treatment alone.

Detailed description: The investigators plan to conduct a prospective, single-center, single-arm, open-label study with 20 acute basilar artery occlusion patients with premorbid modified Rankin Score (mRS) ≤3, treated with standard treatment (mechanical thrombectomy ± intravenous thrombolysis with alteplase or conservative treatment) and Cerebrolysin as add-on therapy, compared with historical controls.

All participants will receive the same standard of care and will be treated according to the latest European Stroke Organisation and American Stroke Organisation guidelines on acute stroke.

Besides standard acute stroke assessment, treatment, and acute rehabilitation, the participants who meet the eligibility criteria, are informed about the study and its potential risks, and have written informed consent, will receive Cerebrolysin in a single-day dosage of 30 ml intravenously for 14 consecutive days. The Cerebrolysin administration will start no earlier than one hour after the standard treatment, and no later than 24 hours after the stroke symptom onset. All possible side-effects will be closely monitored and in case of any adverse effect, the drug administration will be stopped, and the participant will be excluded from the further trial.

The participants will be closely monitored and the data on possible drug side effects, adverse effects, clinical findings, laboratory findings, and neuroimaging findings will be stored in the centralized hospital database. The clinical assessment and imaging analysis will be performed by an unbiased third-party neurologist/neuroradiologist.

The clinical findings and outcomes will be quantified by the National Institutes of Health Stroke Scale (NIHSS) 24 hours, 14 days, 30 days, and 90 days post-stroke and by the Modified Rankin Scale on discharge and 90 days post-stroke. The participants will undergo CT/ MRI neuroimaging for intracranial bleeding detection during admission, 24 hours after the stroke, and on discharge from the hospital. An additional imaging will be performed if indicated.

The interventional group and historical controls will be matched 1:1 based on the site of the basilar artery occlusion (proximal, middle, distal part), and further matched by the National Institutes of Health Stroke Scale score on admission to hospital (0-4, 4-15,16-20, 21-42), premorbid Modified Rankin Scale score, MSCT brain findings on admission to hospital (ischemia/ no ischemia), time from symptom onset to treatment (0-3h, 3-6h, later than 6 h), age (+/- 5 years), type of treatment (conservative treatment, intravenous thrombolysis with alteplase, mechanical thrombectomy, intravenous thrombolysis with alteplase + mechanical thrombectomy), type of mechanical thrombectomy (intracranial basilar artery stenting performed/not performed), and comorbid arterial hypertension (yes or no).

The data for historical controls will be obtained retrospectively from the Central Hospital Database which contains demographic, clinical, laboratory, and neuroimaging records of all patients with posterior circulation stroke secondary to basilar artery occlusion treated in the same Center from January 2015 to May 2024. The data will be analyzed, and the results will be compared between the investigational group and historical controls.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Acute basilar artery occlusion confirmed on MSCT/ MR angiography
* Premorbid mRS ≤ 3
* Signed written consent

Exclusion Criteria:

* Hypersensitivity to one of the components of the drug
* Breastfeeding and pregnancy
* Epilepsy, epileptic seizure
* Severe renal impairment (grade IV and V)
* Ischemic stroke in the previous three months
* Metastatic cancer
* Sepsis or a severe infection on admission
* Acute coronary syndrome, pulmonary embolism, and deep venous thrombosis on admission

Primary outcomes:
measure: Percentage of participants in the Cerebrolysin group with the Modified Rankin Scale (mRS) score 0-3 at 90 days post-stroke compared to historical controls
timeFrame: 90 days (3 months) after the stroke
measure: Mortality rate in the Cerebrolysin group compared to historical controls
timeFrame: 90 days (3 months) after the stroke
Secondary outcomes:
measure: Change in any and symptomatic intracerebral bleeding in the Cerebrolysin group compared to historical controls
timeFrame: 24 hours and 14 days after the stroke
measure: Change in the National Institutes of Health Stroke Scale (NIHSS) compared to historical controls
timeFrame: 24 hours, 14 days, and 90 days after the stroke
Other outcomes:
Locations:
Study officials:
affiliation: Sestre milosrdnice University Hospital Center
name: Marina Roje Bedeković, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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