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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska Institutet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

11 Nov 2025 → ongoing

Decision date (initial)

2023-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Vetenskapsrådet · ALF Medicin · Hjärt-Lungfonden

External identifiers

EU CT number

2023-506178-11-00

EudraCT number

2017-000075-85

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate if Imatinib (800 mg / day) treatment initiated within 8 hours of symptom onset and given for 6 days improves functional outcome at three months after acute ischaemic stroke

Secondary objectives 8

1. 1) Investigate if Imatinib treatment improves functional outcome at three months in acute ischaemic stroke patients treated with iv thrombolysis
2. 2) Investigate if Imatinib treatment improves neurological outcome at three months after acute ischaemic stroke
3. 3) Investigate if Imatinib treatment improves neurological outcome at three months in acute ischaemic stroke patients treated with iv thrombolysis
4. 4) Investigate if Imatinib reduces the frequency and grade of ICH in patients with acute ischaemic stroke treated with iv thrombolysis
5. 5) Investigate if Imatinib reduces the frequency and grade of cerebral oedema in patients with acute ischaemic stroke treated with iv thrombolysis
6. 6) Examine serious and non-serious adverse events in patients treated with Imatinib
7. 7) Investigate if Imatinib reduces mortality at 3 months after acute ischaemic stroke
8. 8) Investigate if Imatinib reduces mortality at 3 months in acute ischaemic stroke patients treated with iv thrombolysis

Conditions and MedDRA coding

Acute ischemic stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1) Clinical diagnosis of acute ischaemic stroke with a neurological deficit corresponding to 6 points or higher on the NIHSS score.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. 2) Age 18-89 years
3. 3) Patients should be randomised as soon as possible but not later than 8 hours of symptom onset/ last known well or patients who present with a wake up stroke (WUS) who can be randomised within 6 hours from awakening provided the other criteria are met. a) If the patient receives iv thrombolysis alone, patient should be randomised and study drug should be given withinone 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. 4) iv thrombolysis, if performed, is done in agreement with European Stroke Organisation (ESO) guidelines 2021* and has been initiated within 4.5 hours of stroke onset (see below separate criteria for indications / contraindications)
5. 5) Endovascular thrombectomy, if performed, is done in agreement with ESO guidelines 2019**, 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 or first segment of the Posterior Cerebral Artery (P1), consistent with the clinical symptoms. b) thrombectomy has been initiated within 8 hours of symptom onset/last known well or within 6 hours of WUS (defined as start of Arterial puncture)
6. 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

Exclusion criteria 18

1. 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. 2) Known significant pre-stroke disability (mRS ≥2)
3. 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. 4) Acute pancreatitis
5. 5) Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
6. 6) Ongoing treatment with chemotherapy
7. 7) Drugs which may increase the plasma concentration of Imatinib -– ketokonazol, itrakonazol, erythromycin and claritomycin
8. 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. 9) Female patients with childbearing potential, if pregnancy cannot be excluded by pregnancy test (urine point-of-care pregnancy test).
10. 10) Patient is participating in other interventional study
11. Additional Exclusion criteria for patients treated with intravenous thrombolysis (IVT):
12. 1) 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.
13. 2) Patients receiving oral anticoagulants, e.g. warfarin sodium (INR>1.7) or direct oral anticoagulation: dabigatran (aPTT>40s), apixaban, rivaroxaban.
14. 3) Platelet count below 100,000/mm3. Significant bleeding disorder at present or within the past 6 months, known haemorrhagic diathesis
15. 4) History or evidence or suspicion of intracranial haemorrhage including sub-arachnoid haemorrhage
16. 5) 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.
17. 6) 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
18. 7) Major surgery or significant trauma in the past 10 days

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in modified Rankin Scale (mRS) score at 3 months, favourable shift of the scale in the Imatinib group compared to placebo.

Secondary endpoints 5

1. 1) Functional independency at 3 months as measured by modified Rankin Scale (mRS) Score 0-2. For a positive outcome, patients in the active group treated with Imatinib 800 mg per day will have statistically significant higher functional independency compared to the control group treated with placebo
2. 2) Neurological outcome at 24 h and at 7 days or discharge if occurs earlier and at 3 months
3. 3) Frequency and grade of ICH and cerebral oedema on post-treatment imaging scan in patients undergoing IV thrombolysis and or endovascular thrombectomy,
4. 4) Serious and non-serious adverse events
5. 5) Mortality at 3 months

Investigational products

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

Test 2

Placebo 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Nobels Vag 6

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Karolinska Institutet

Contact name

Niaz Ahmed

Public contact point

Organisation

Karolinska Institutet

Contact name

Niaz Ahmed

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Application history

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