Imatinib in Acute Ischaemic Stroke

NCT03639922 | Unknown Phase 3 DMC

• 2 other identifiers: I-StrokeII20162017-000075-85
• Study Type: interventional
• Target: 1,260
• Locations: 1 country
• Sites: 17

Brief Summary

A clinical trial comparing treatment with Imatinib to placebo when administered within 8 hours of stroke onset for 6 days, in addition to conventional stroke treatment after acute ischaemic stroke.

Conditions

Acute Ischaemic Stroke

Keywords

acute ischaemic stroke; Imatinib; blood-brain-barrier; trombectomy; iv trombolysis

Outcome Measures

Primary Outcomes (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.

  3 months post treatment

Secondary Outcomes (7)

• Change in mRS score at 3 months compared to baseline

  At baseline and 3 months post treatment

• Frequency (%) of ICH on post-treatment imaging scan in patients undergoing IV thrombolysis and or endovascular thrombectomy.

  1 day post treatment start

• Grade of ICH (COED 1-3) on post-treatment imaging scan in patients undergoing IV thrombolysis and or endovascular thrombectomy.

  1 day post treatment start

• Frequency (%) of cerebral oedema on post-treatment imaging scan in patients undergoing IV thrombolysis and or endovascular thrombectomy.

  1 day post treatment start

• Grade (COED 1-3) of cerebral oedema on post-treatment imaging scan in patients undergoing IV thrombolysis and or endovascular thrombectomy.

  1 day post treatment start

Study Arms (2)

Imatinib

ACTIVE COMPARATOR

Imatinib 400mg (2 tablets of 400mg) per day for 6 days

Drug: Imatinib 400mg

Placebo

PLACEBO COMPARATOR

2 placebo tablets per day for 6 days

Drug: Placebo Oral Tablet

Interventions

Imatinib 400mg DRUG

2 tablets of Imatinib 400mg per day for 6 days

Imatinib

Placebo Oral Tablet DRUG

2 tablets of placebo per day for 6 days

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of acute ischaemic stroke with a neurological deficit corresponding to 6 points or higher on the NIHSS score
• at the time of randomization if no recanalisation therapy performed
• prior to iv thrombolysis therapy alone or prior to thrombectomy alone if performed
• 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.
• Age 18-85 years
• Patients should be randomized as soon as possible but not later than 8 hours of symptom onset.
• If the patient receives iv thrombolysis alone, patient should be randomized and study drug should be given within one hour after completion of iv thrombolysis infusion
• If the patient receives endovascular thrombectomy (with or without prior iv thrombolysis), patient should be randomized within two hours after completion of endovascular thrombectomy and study drug given as soon as possible after randomization.
• 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)
• Endovascular thrombectomy, if performed, is done in agreement with recently published American Stroke Association guidelines, and fulfilling the following criteria
• 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.
• thrombectomy has been initiated within 8 hours of symptom onset (defined as start with femoral artery (groin) puncture)
• 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

You may not qualify if:

• General
• 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
• ) Known significant pre-stroke disability (mRS ≥2)
• 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.
• Acute pancreatitis
• Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
• Ongoing treatment with chemotherapy
• Drugs which may increase the plasma concentration of Imatinib - ketokonazol, itrakonazol, erythromycin and claritomycin
• Drugs which may decrease the plasma concentration of Imatinib: Dexametason, phenytoin, karbamazepin, rifampizin, phenobarbital, fosphenytoin, primidon, Hypericum perforatum (Johannesört, St John's wort)
• Female patients with childbearing potential, if pregnancy cannot be excluded by pregnancy test (urine point-of-care pregnancy test).
• Patient is participating in other interventional study
• Severe stroke as assessed clinically by NIHSS\>25
• 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.
• Patients receiving oral anticoagulants, e.g. warfarin sodium (INR\>1.7) or direct oral anticoagulation: dabigatran ( aPTT\>40s), apixaban, rivaroxaban.
• Platelet count below 100,000/mm3. Significant bleeding disorder at present or within the past 6 months, known haemorrhagic diathesis.

Sponsors & Collaborators

• Niaz Ahmed: lead

Study Sites (17)

Mälarsjukhuset Eskilstuna

Eskilstuna, 633 49, Sweden

NOT YET RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, 413 45, Sweden

RECRUITING

Hässleholms sjukhus

Hässleholm, 28151, Sweden

RECRUITING

Centralsjukhuset Karlstad

Karlstad, 65185, Sweden

RECRUITING

Centralsjukhuset Kristianstad

Kristianstad, 291 85, Sweden

RECRUITING

Skånes Universitetssjukhus Lund

Lund, 221 85, Sweden

NOT YET RECRUITING

Skånes Universitetssjukhus Malmö

Malmo, 205 02, Sweden

NOT YET RECRUITING

Skaraborgs sjukhus Skövde

Skövde, 541 42, Sweden

RECRUITING

Capio S:t Görans Hospital

Stockholm, 112 81, Sweden

RECRUITING

Södersjukhuset

Stockholm, 118 83, Sweden

RECRUITING

Karolinska Universitetssjukhuset Huddinge

Stockholm, 141 86, Sweden

RECRUITING

Karolinska Universitetssjukhuset Solna

Stockholm, 171 76, Sweden

RECRUITING

Danderyds sjukhus

Stockholm, 182 88, Sweden

RECRUITING

Sundsvalls Sjukhus

Sundsvall, 856 43, Sweden

NOT YET RECRUITING

Umeå University Hospital

Umeå, 90185, Sweden

NOT YET RECRUITING

Uppsala Akademiska Sjukhus

Uppsala, 751 85, Sweden

RECRUITING

Västmanlands sjukhus Västerås

Västerås, 721 89, Sweden

RECRUITING

MeSH Terms

Interventions

Imatinib Mesylate

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Niaz Ahmed, MD PhD

  Karolinska Institutet

  STUDY DIRECTOR

Central Study Contacts

Niaz Ahmed, MD PhD

CONTACT

+ 46 8-517 72026; niaz.ahmed@ki.se

Marie Westman, PhD

CONTACT

+ 46 8-517 75034; marie.westman@sll.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study is double-blind, only after the study is completed or terminated the treatments will be made available, or if requested by the data safety board, or if requested by treating clinician in association with possible SAE/SUSAR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor, Coordinating investigator

Model Details: randomized, double-blind, placebo-controlled, parallel-arm

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 21, 2018
• Study Start: October 1, 2018
• Primary Completion: December 1, 2022
• Study Completion: June 1, 2023
• Last Updated: September 16, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (17)