Evaluation of Mechanical Thrombectomy Plus Acetylsalicylic Acid Versus Acetylsalicylic Acid Alone in Acute Ischemic Stroke with Large Vessel Occlusion

Trial ID: 2024-515062-13-00
Protocol: NBK241/2/2022
Sponsor: Medical University Of Gdansk

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Diseases & Conditions

Ischaemic stroke

Objectives

The primary objective of this study is to evaluate the efficacy of **mechanical thrombectomy** in conjunction with standard treatment, including acetylsalicylic acid, compared to standard treatment alone in patients with **acute ischemic stroke** due to large vessel occlusion. The assessment will be based on the functional outcome score using the modified Rankin Scale, which includes patient mortality, after 90 days. This is clinically relevant as it aims to determine if the addition of mechanical thrombectomy can improve outcomes in patients who have an initial neurological deficit with NIHSS ≥ 5, potentially leading to better recovery and reduced mortality.

Secondary objectives include:

Evaluating the safety of the investigated treatment by reporting all adverse and serious adverse events, with a focus on vessel perforation, embolism migration to new territory, and symptomatic bleeding complications rates.
Assessing the impact of the proposed treatment on the patients' quality of life.

Participants

The clinical trial involves participants diagnosed with **acute ischemic stroke** caused by the occlusion of a large vessel. The study population includes both male and female adults over the age of 18, with no specific vulnerable populations selected. The sponsor has not provided the total number of participants. Participants were selected based on their ability to provide informed consent, either written or verbal, confirmed by an independent witness if necessary. The trial includes individuals with a neurological deficit assessed between 5-18 points on the NIHSS scale, and those with a current DWI-FLAIR mismatch. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial population was chosen to assess the efficacy of mechanical thrombectomy in addition to standard treatment, including acetylsalicylic acid, compared to standard treatment alone.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **mechanical thrombectomy** in conjunction with standard treatment, including **acetylsalicylic acid**, compared to standard treatment alone in patients with **acute ischemic stroke** due to large vessel occlusion. This study is a randomized, double-blind, controlled trial, with an estimated duration extending until June 2027. The trial will assess the primary endpoint of functional outcome using the modified Rankin Scale at 90 days, alongside secondary endpoints such as changes in NIHSS scores and quality of life assessments.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, neurological deficit, and imaging results. Following randomization, participants will receive either the intervention or control treatment. Follow-up visits will occur at 24 hours, 48 hours, 7 days, and 90 days post-treatment to monitor clinical efficacy and safety endpoints, including symptomatic intracerebral hemorrhage. The end-of-study visit will coincide with the 90-day assessment, marking the conclusion of participant involvement.

Participant involvement is expected to last approximately 90 days, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial aims to provide robust data on the potential benefits of mechanical thrombectomy in this patient population, contributing to the optimization of treatment strategies for acute ischemic stroke.

Treatment

The clinical trial involves the use of **acetylsalicylic acid** as part of the treatment regimen for patients with acute ischemic stroke due to large vessel occlusion. **Acetylsalicylic acid** is administered in the form of a **tablet** and is of chemical origin. The route of administration is **oral**, with a maximum daily dose of 75 mg and a maximum total dose of 150 mg over the course of the treatment period, which is limited to one day. The medication is not a pediatric formulation and is not classified as an orphan drug. The role of **acetylsalicylic acid** in this trial is as a test product, and it is used in conjunction with mechanical thrombectomy to evaluate its efficacy in improving functional outcomes as measured by the modified Rankin Scale after 90 days.

In addition to the experimental treatment, the study includes standard treatment protocols that incorporate **acetylsalicylic acid** as a non-experimental treatment. The trial aims to determine whether the addition of mechanical thrombectomy to the standard treatment, which includes **acetylsalicylic acid**, offers superior outcomes compared to the standard treatment alone. Compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen, and the trial's main objective is to assess the impact on patient mortality and neurological function.

Efficacy

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary clinical efficacy endpoints include the achievement of a favorable outcome on the modified Rankin Scale (mRS), defined as an mRS score of less than or equal to 2, at 90 days post-treatment. Additionally, changes in the volume of the hyperintense area in the DWI and FLAIR sequences will be measured at baseline, 7 days, and 90 days, where possible. These assessments will help determine the effectiveness of the treatment in improving functional outcomes and reducing ischemic damage.

Secondary endpoints will focus on the reduction in the National Institutes of Health Stroke Scale (NIHSS) scores, with specific reductions of 4 and 8 points being evaluated separately at 24 hours, 48 hours, and 7 days. The patient's quality of life will be assessed using the Beck Depression Rating Scale, the EQ-5D-5L Scale, and the Barthel Scale. Furthermore, the technical outcome of the procedure will be evaluated by grading the degree of recanalization using the Thrombolysis in Cerebral Ischemia (TICI) scale. These secondary measures will provide additional insights into the treatment's impact on neurological recovery and overall patient well-being.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Obtaining informed consent to participate in the trial prior to randomization. NOTE: Patients whose severe neurological deficit makes it impossible to sign the consent form may give their verbal consent to participate in the study. This consent should be additionally confirmed by the signature of an independent witness who is not a family member of the patient and does not participate in the study. Patients with aphasia and / or other speech disorders may be enrolled in the study if, in the opinion of the recruiting neurologist or neurologist in training, they are able to understand the study concept.
Adult patients with acute ischemic stroke due to the occlusion of a large intracranial or extracranial vessel (angio-CT or angio-MR) in a place that allows mechanical recanalization using a stent-retriever.
Current DWI-FLAIR mismatch. In the WAKE-IN study, a DWI-FLAIR mismatch is defined as: No hyperintense change in the FLAIR sequence corresponding to acute ischemia in DWI or the ratio of the volume of restriction of diffusion in the DWI sequence (hyperintensive lesion) to the corresponding hyperintense lesion volume in the FLAIR sequence 1.5 or higher. Note: The presence of other changes in the FLAIR sequence, such as "chronic" white matter lesions, do not exclude from participation in the study.
The neurological deficit was assessed at 5-18 points on the NIHSS scale.
Age>18 years of age.
Arm A: 1.Unknown time of onset (not more than 24 hours from when the patient was symptom-free), or the time from onset to estimated arterial puncture between 6 and 24 hours.
Arm A: 2. Failure to meet the DAWN and DEFUSE-3 eligibility criteria.
Arm B: 1.From 0 to 5 points on the ASPECTS scale.
Arm B: 2. Time from the first symptoms of acute stroke to arterial puncture not exceeding 6 hours.

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Exclusion Criteria

Significant disability prior to the current event defined as > 2 points on the modified Rankin Scale (mRS) and/or significant cognitive impairment prior to the current event (documented in the patient's medical records).
Known heart failure (if medical history available) with EF <25%; in the absence of information without the need for testing at the randomization stage.
Acute pancreatitis.
Severe renal failure (eGFR <30 ml / min / 1.73 m2).
Suspected systemic vasculitis or primary central nervous system vasculitis.
Severe liver disease, including liver failure, cirrhosis, or portal hypertension.
Platelet count <100,000/mm3.
Glucose concentration <50 mg/dl (2.8 mmol/l) or >400 mg/dl (22.2 mmol/l) immediately before the intervention.
MRI contraindications or inability to identify contraindications.
Intracranial bleeding in neuroimaging (CT or MRI of the brain).
Neuroimaging pathologies other than ischemia-related pathologies that may be responsible for acute symptoms.
Significant pathologies detected accidentally in neuroimaging (e.g. tumor, giant aneurysm, massive brain atrophy).
Clinical suspicion of subarachnoid bleeding (even if the CT or MRI result is normal).
Clinical suspicion of cerebral venous sinus thrombosis.
Previous or chronic disease of the central nervous system that significantly impairs the functional state and/or has a poor prognosis (brain tumors, aneurysms, arteriovenous malformations, open brain surgery with dura mater/dural incision).
Infective endocarditis or pericarditis.
Very high blood pressure, i.e. systolic blood pressure>185 mm Hg or diastolic blood pressure >110 mm Hg immediately before the intervention. NOTE: If pharmacological intervention (e.g., bolus administration of labetalol or urapidil, or in the absence of a satisfactory continuous infusion response via an infusion pump) has produced a satisfactory response (blood pressure <185/110 mmHg) prior to randomization and / or initiation of treatment and in the opinion of the physician, adequate blood pressure control can be maintained throughout the course of treatment, the patient will be enrolled in the study.
Pregnancy or breast-feeding.
Life expectancy <3 months, participation in another clinical trial at the time of randomization or planned enrollment in another clinical trial within less than 30 days from randomization, provided that there is pathophysiological or formal-administrative interference in the protocols of these studies.