Treatment of acute ischemic stroke due to occlusion of a large vessel by mechanical thrombectomy in patients with unknown onset or not meeting the criteria for CT eligibility (ASPECTS <6) based on MRI criteria (DWIFLAIR mismatch)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Jan 2025 → ongoing

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency (Agencja Badań Medycznych)

External identifiers

EU CT number

2024-515062-13-00

EudraCT number

2022-001287-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The main objective of this study is to assess whether the mechanical thrombectomy added to standard treatment including acetylsalicylic acid is superior to standard treatment alone including acetylsalicylic acid, in patients with acute ischemic stroke due to large vessel occlusion and initial neurological deficit NIHSS ≥ 5, using functional outcome score with modified Rankin Scale, that includes patient mortality, after 90
days.

Secondary objectives 2

1. Safety of the investigated treatment based on reporting all adverse and serious adverse events with focus on vessel perforation, embolism migration to new territory, and symptomatic bleeding complications rates.
2. The impact of the proposed treatment on the patients' quality of life.

Conditions and MedDRA coding

acute ischemic stroke caused by occlusion of a large vessel

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. 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.
3. 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.
4. The neurological deficit was assessed at 5-18 points on the NIHSS scale.
5. Age>18 years of age.
6. 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.
7. Arm A: 2. Failure to meet the DAWN and DEFUSE-3 eligibility criteria.
8. Arm B: 1.From 0 to 5 points on the ASPECTS scale.
9. Arm B: 2. Time from the first symptoms of acute stroke to arterial puncture not exceeding 6 hours.

Exclusion criteria 19

1. 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).
2. Known heart failure (if medical history available) with EF <25%; in the absence of information without the need for testing at the randomization stage.
3. Acute pancreatitis.
4. Severe renal failure (eGFR <30 ml / min / 1.73 m2).
5. Suspected systemic vasculitis or primary central nervous system vasculitis.
6. Severe liver disease, including liver failure, cirrhosis, or portal hypertension.
7. Platelet count <100,000/mm3.
8. Glucose concentration <50 mg/dl (2.8 mmol/l) or >400 mg/dl (22.2 mmol/l) immediately before the intervention.
9. MRI contraindications or inability to identify contraindications.
10. Intracranial bleeding in neuroimaging (CT or MRI of the brain).
11. Neuroimaging pathologies other than ischemia-related pathologies that may be responsible for acute symptoms.
12. Significant pathologies detected accidentally in neuroimaging (e.g. tumor, giant aneurysm, massive brain atrophy).
13. Clinical suspicion of subarachnoid bleeding (even if the CT or MRI result is normal).
14. Clinical suspicion of cerebral venous sinus thrombosis.
15. 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).
16. Infective endocarditis or pericarditis.
17. 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.
18. Pregnancy or breast-feeding.
19. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary clinical efficacy endpoints: • mRS favorable (mRS less than or equal to 2) at 90 days. • Change in hyperintense area volume in the DWI and FLAIR sequences between baseline, 7 days and 90 days (where possible). Primary safety endpoints: • Symptomatic intracerebral haemorrhage (sICH) assessed with ECASS 2 criteria within 24 hours (any intracranial haemorrhage with neurological deterioration of at least 4 points on the NIHSS or any fatal haemorrhage)

Secondary endpoints 1

1. • Reduction in NIHSS ≥ 4 and ≥ 8 points separately at 24 hrs, 48 hrs, and 7 days • The patient's quality of life within selected domains with Beck Depression Rating Scale, the EQ-5D-5L Scale and the Barthel Scale. • The technical outcome of the procedure (grading the degree of recanalization) assessed with the Thrombolysis in Cerebral Ischemia (TICI) scale.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Chief Medical Officer; Principal Investigator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Director of Clinical Research Support Centre

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications