Health Condition 1: I63- Cerebral infarction
Conditions
Interventions
Intervention1: Tenecteplase: Dose: One single dose bolus administration
Route: i.v
Duration: 90 days
Control Intervention1: Standard of Care: Standard of Care
Sponsors
Boehringer Ingelheim International GmbH
IQVIA RDS INDIA PRIVATE LIMITED
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female more than 18 years old and at least at the legal age of consent in countries where it is greater than 18 years 2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. See Section 8.1 for details. 3. Acute ischaemic stroke (including wake-up stroke) affecting the supratentorial circulation (anterior [ACA], middle [MCA], and posterior cerebral arteries [PCA]) last known well more than 4.5 h before time of presumed randomisation 4. Pre-stroke mRS less than equals to 1 5. Imaging eligibility (either a, b or c): a) MRI criteria (both must be met) Mismatch Ratio: The area of reduced blood flow at risk on MRI (perfusion lesion) is at least 1.2 times (20 percent) larger than the area of established brain injury (DWI lesion) Mismatch Volume: The difference between the perfusion lesion and DWI lesion is more than 10 mL. b) NCCT-CT Perfusion criteria (both must be met) The area of reduced blood flow at risk on CT perfusion (perfusion lesion) is at least 1.2 times (20 percent) larger than the estimated ischemic core lesion AND lesion on NCCT is not larger than the estimated ischemic core lesion The mismatch volume is more than 10 mL c) If neither MRI or CT perfusion are available at the site (both must be met) CTA depicting blood vessel blockage: Presence of a blockage in specific supratentorial circulation brain arteries M1 or M2 segments of the Middle Cerebral Artery (MCA) Small lesion on NCCT: ASPECTS more than equals to 7 with M1 MCA occlusions; for M2 MCA occlusions, a maximum of 1 ASPECTS regions involved distal to the occlusion (ASPECTS 9-10)
Exclusion criteria
Exclusion criteria: 1. Intention to proceed to MT at the same site (hospital) of randomisation 2. Occlusion of the internal carotid artery (ICA) 3. High-risk patients (increased risk of thrombolysis related hemorrhage), defined as: a. Large brain infarcts: i. On MRI: area of brain injury by DWI more than equals to 70 mL ii. On CT perfusion: estimated ischemic core more than equals to 70 mL iii. On NCCT: ASPECTS score between 0-6 b. Severely injured brain tissue: i. On NCCT Patients whose brain lesion shows intense hypo-attenuation when compared to the normal white matter on the opposite side 4. Any intracranial hemorrhage detected on NCCT or MRI scans 5. Contra-indication to contrast brain imaging with CT and MRI 6. Non-disabling minor stroke symptoms (NIHSS less than equals to 5), or rapidly improving symptoms at the discretion of the investigator. 7. Imaging or clinical findings not indicative of acute ischemic stroke or suggesting stroke older than 72 h 8. Patients scheduled to receive i.v. thrombolysis as standard of care 9. Other known or identified relevant central nervous system damage (example neoplasm, arterial aneurysm and or arterial venous malformation, intracranial or spinal surgery) 10. Severe stroke as assessed clinically (NIHSS more than 25) 11. Platelet count below 100 000 per mm 12. Anticoagulant use with following attributes: a. If on Vitamin K antagonists, INR more than 1.7 or prothrombin time more than 15 seconds; b. use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours; c. any full dose heparin heparinoid during the last 24 hours or with an aPTT greater than the upper limit of normal 13. Arterial puncture at a non-compressible site or lumbar puncture within 7 days 14.Acute pancreatitis 15. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis 16. Severe uncontrolled arterial hypertension that cannot be reverted by anti-hypertensive drugs (example systolic BP more than 185 mmHg, or diastolic BP more than 110 mmHg) 17. Known severe renal impairment (eGFR 2 minutes) within the past 2 weeks 18. Active ulcerative gastro-intestinal disease 19. Any history of prior stroke and concomitant diabetes 20. Major surgery, biopsy of a parenchymal organ, recent trauma to the head or significant trauma within the past 2 weeks 21. Prolonged cardiopulmonary resuscitation ( more than 2 minutes) within the past 2 weeks 22. Acute pericarditis and or subacute bacterial endocarditis 23. Active peptic ulceration 24. Any known history of haemorrhagic stroke 25. Known history of ischaemic stroke or transient ischaemic attack in the preceding 3 months 26. Women who are pregnant or breastfeeding 27. Hypersensitivity to the active substance or to any of the tenecteplase excipients listed, or to gentamicin (a trace residue from the manufacturing process)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To test the hypothesis that i.v. tenecteplase (0.25 mg per kg, maximum 25 mg) is superior to standard of care (that does not include thrombolytic medication) in achieving excellent functional outcome (modified Rankin Scale (mRS) score of 0-1 at Day 90) in AIS participants who were last known well more than 4.5 hours before randomisation (including strokes of known and unknown onset, to which wake up strokes belong), and presenting with a significant volume of salvageable brain tissue on imagingTimepoint: day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess safety of tenecteplase in patients in this setting & efficacy in key functional outcomesTimepoint: Efficacy mRS (ordinal) at Day 90 Early neurological improvement (reduction in acute 24-hour NIHSS score of more than equals to 8 or value of 0/1) mRS 0-2 at Day 90 Safety sICH as defined by SITS-MOST criteria at 36 h sICH as defined by ECASS III criteria at 36 h Death from any cause within 90 days | — |
Countries
Argentina, Australia, Bulgaria, China, Greece, Hungary, India, Indonesia, Kazakhstan, Malaysia, Norway, Romania, Spain, Taiwan, Thailand, Viet Nam
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed