A phase 3, randomised, double-blind, placebo-controlled, parallel-arm efficacy trial of Imatinib in acute ischaemic stroke

Phase 1

• Conditions: Patients with acute ischaemic stroke and an imaging scan excluding any intracranial haemorrhage; MedDRA version: 22.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 22.1Level: LLTClassification code 10055221Term: Ischemic strokeSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-000075-85-SE
• Lead Sponsor: Karolinska Institutet

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-24
• Last Update Posted: 28 June 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 680

Inclusion Criteria

1) Clinical diagnosis of acute ischaemic stroke with a neurological deficit corresponding to 6 points or higher on the NIHSS score
a) at the time of randomisation if no recanalisation therapy performed
b) prior to iv thrombolysis therapy alone or prior to thrombectomy alone if performed
c) prior to iv thrombolysis if both iv thrombolysis and thrombectomy performed
Ischaemic stroke is defined as an event characterised by sudden onset of acute focal neurological deficit, presumed to be caused by cerebral ischaemia and an imaging scan excluding any intracranial haemorrhage.
2) Age 18-85 years
3) Patients should be randomised as soon as possible but not later than 8 hours of symptom onset.
a) If the patient receives iv thrombolysis alone, patient should be randomised and study drug should be given within one hour after completion of iv thrombolysis infusion
b) If the patient receives endovascular thrombectomy (with or without prior iv thrombolysis), patient should be randomised within two hours after completion of endovascular thrombectomy and study drug given as soon as possible after randomisation.
4) iv thrombolysis, if performed, is done in agreement with European Stroke Organisation guidelines and has been initiated within 4.5 hours of stroke onset (see below separate criteria for indications / contraindications)
5) Endovascular thrombectomy, if performed, is done in agreement with the recently published American Stroke Association guidelines, and fulfilling the following criteria
a) Confirmed diagnosis on Computed Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) of acute occlusion of either of the first two segments of the Middle Cerebral Artery (M1 or M2), terminal Carotid Artery, first segment of the Anterior Cerebral Artery (A1), or Basilar Artery, consistent with the clinical symptoms.
b) thrombectomy has been initiated within 8 hours of symptom onset (defined as start of Arterial puncture)
6) Patient is competent to make a decision and has provided informed consent with regard to participation in the study, retrieval and storage of data and follow up procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 480

Exclusion Criteria

General
1) Imaging scans show signs of large current infarction as defined by more than 1/3 of the Middle Cerebral Artery territory or ½ of other vascular territories
2) ) Known significant pre-stroke disability (mRS =2)
3) Severe comorbidities such as advanced dementia (estimate pre-stroke if otherwise healthy), terminal illness, and other severe medical conditions with anticipated life expectancy less than 6 months.
4) Acute pancreatitis
5) Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
6) Ongoing treatment with chemotherapy
7) Drugs which may increase the plasma concentration of Imatinib - ketokonazol, itrakonazol, erythromycin and claritomycin
8) Drugs which may decrease the plasma concentration of Imatinib: Dexametason, phenytoin, karbamazepin, rifampizin, phenobarbital, fosphenytoin, primidon, Hypericum perforatum (Johannesört, St John's wort)
9) Female patients with childbearing potential, if pregnancy cannot be excluded by pregnancy test (urine point-of-care pregnancy test).
10) Patient is participating in other interventional study

Additional Exclusion criteria for patients treated with intravenous thrombolysis (IVT)
1) Severe stroke as assessed clinically by NIHSS>25
2) Administration of heparin within the previous 48 hours preceding the onset of stroke with an elevated activated thromboplastin time (aPTT) at presentation, or corresponding low-molecular heparin.
3) Patients receiving oral anticoagulants, e.g. warfarin sodium (INR>1.7) or direct oral anticoagulation: dabigatran ( aPTT>40s), apixaban, rivaroxaban.
4) Platelet count below 100,000/mm3. Significant bleeding disorder at present or within the past 6 months, known haemorrhagic diathesis.
5) History or evidence or suspicion of intracranial haemorrhage including sub-arachnoid haemorrhage
6) Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, in spite of repeated doses of i.v. medication to reduce blood pressure below these limits.
7) History of the following conditions: prior ischemic stroke within 3 months, intra-axial neoplasm, intracranial or spinal surgery within the prior 3 months, recent severe head trauma within 3 months or unruptured intracranial aneurysm>5 mm.
8) Major surgery or significant trauma in the past 10 days

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified