ALTEPLASE for Acute ischemic stroke

Inclusion criteria

• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 1.\tObtaining informed consent to participate in the trial. NOTE: Patients whose neurological deficit is severe enough to make it impossible to sign the consent form are allowed to give only their oral consent to participate in the study. However, this consent should be additionally certified by the signature of two independent witnesses (who are neither family members of the patient nor the STROACT study staff) or by the signature of his/her legal representative. Patients with aphasia and/or other speech disorders may be included into the study if following neurological assessment of the recruiting stroke physician, they are able to understand all important information about the study."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 2.\tAge >18 years."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 3.\tClinical diagnosis of acute ischemic stroke (sharply defined onset of first symptoms) resulting in a disabling neurological deficit."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 4.\tTherapy with an oral anticoagulant that is the non-vitamin K antagonist oral anticoagulant (apixaban or rivaroxaban) with laboratory confirmed therapeutic anti-Xa activity measured as a plasma concentration > 50 ng/mL."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 5.\tAdministration of study intervention (intravenous thrombolysis with alteplase) should be possible to start within 4.5 hours from AIS symptoms onset or the last time the patient was seen without symptoms, as per investigator’s judgment. NOTE: If a patient was enrolled and there was a clear clinical reason for delaying the start of the study intervention within the 4.5-hour window, the patient may still be included in the study if rtPA can be given within 6.0 hours of the onset of acute ischemic stroke. NOTE: In patients recruited to STROACT study, in addition to the inclusion / exclusion criteria, apply all standard clinical practice indications and contraindications for rtPA administration in acute ischemic stroke unless stated otherwise in this protocol."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 1. Age ≥ 18 years."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 2. Clinical diagnosis of acute ischemic stroke (with sharply defined onset of first symptoms or last known well within 24 hours with laboratory confirmed therapeutic anti-IIa/Xa activity measured as a plasma concentration >50 ng/mL)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 3. Therapy with an oral anticoagulant that is the non-vitamin K antagonist oral anticoagulant (dabigatran, apixaban or rivaroxaban) with laboratory confirmed therapeutic anti-IIa/Xa activity measured as a plasma concentration >50 ng/mL."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 4. The neurological deficit rapidly improved to the point of a non-disabling deficit before obtaining the ICF to participate in the interventional part of the STROACT study."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 5. Obtaining the ICF to participate in the observational part of the STROACT study."}

Exclusion criteria

• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 1. Occlusion of a large intracranial vessel in CT/MR angiography (CTA/MRA), corresponding to the current acute neurological deficit being an indication for primary mechanical thrombectomy."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 2. Significant disability prior to the current stroke event defined as >2 points on the modified Rankin Scale (mRS) and/or significant impairment of the cognitive function prior to AIS (the latter documented in patient’s medical records)."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 3. Mild and rapidly improving neurological deficit with high probability of complete recovery."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 4. Clinically severe stroke with >18 points in NIHSS."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 5. Neuroimaging findings that might be responsible for acute neurological deficit (“stroke mimics”) and/or are contraindications for standard thrombolytic treatment: such as intracranial and/or intracerebral bleeding, tumours, abscesses and other."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 6. Treatment with the following anticoagulants: a. Oral vitamin K antagonist (warfarin, acenocumarol), b. Unfractionated heparin, c. Low molecular weight heparin, or d. Inhibitors of coagulation factor IIa (dabigatran) and Xa other than rivaroxaban or apixaban"}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 7. Whole blood, and/or blood clotting factors (such as: prothrombin complex concentrate [PCC], recombinant factor VIIa [rVIIa], fresh frozen plasma [FFP]) administered within 7 days before study treatment initiation."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 8. Anti-Xa activity (which is assumed to be directly proportional to the DOAC plasma concentration) is <50 ng/mL."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 9. CT or MRI initial lesion volume >1/2 of the anatomical perfusion area of the middle cerebral artery (MCA), or anterior cerebral artery (ACA), or posterior cerebral artery (PCA)."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 10. Suspected subarachnoid haemorrhage based on specific symptomatology and/or physical examination (even if CT/MRI is normal)."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 11. Any history of subarachnoid or intracerebral haemorrhage, so not including previous (currently normal in neuroimaging) traumatic sub-or epidural hematomas > 6 months before the current acute stroke."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 12. Any past (chronic) medical illnesses that significantly impair patient’s functional status down to mRS 3 points or more (thus not only related to CNS pathologies and including cognitive impairment), and/or with a poor prognosis (e.g., neoplasms individually assessed to be of poor prognosis). NOTE: Patients after treatment of intracranial aneurysm may be considered for recruitment into the STROACT trial if the procedure was performed > 3 months prior to enrollment."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 13. History of major surgery / trauma within 2 months before the current acute stroke."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 14. History of acute ischemic stroke or any other medical condition treated with intravenous thrombolysis, or ischemic stroke treated with mechanical thrombectomy, within the 72 hours preceding the current patient’s stroke symptoms."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 15. Recent (within 10 preceding days) traumatic external heart massage, obstetrical delivery, lumbar puncture, any puncture of a non-compressible blood vessel."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 16. Recent (within 4 preceding weeks) myocardial infarction."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 17. Severe trauma at the onset of acute ischemic stroke (e.g., skull fracture, long bone fracture, pelvic fracture)."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 18. Expected need for major surgery within 72 hours after enrollment (e.g., laparotomy, hip femoral/pelvic fracture surgery, endarterectomy)."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 19.Cerebral venous sinus thrombosis (CVST)."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 20.Pulmonary embolism."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 21.Suspected infective endocarditis and/or pericarditis."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 22.Acute pancreatitis."}
• {"criterion_text":"- INTERVENTIONAL PART OF THE STROACT STUDY: 23.Systemic or suspected cerebral vasculitis."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 1.Occlusion of a large intracranial vessel in CT/MR angiography (CTA/MRA), corresponding to the current acute neurological deficit being an indication for primary mechanical thrombectomy. NOTE 1: Patients who qualified to the mechanical thrombectomy cannot be enrolled to the observational part of the STROACT study."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 2. Significant disability prior to the current stroke event defined as >2 points on the modified Rankin Scale (mRS) and/or significant impairment of the cognitive function prior to AIS (the latter documented in patient’s medical records)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 3. Neuroimaging findings that might be responsible for acute neurological deficit (“stroke mimics”)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 4. Treatment with the following anticoagulants: a. Oral vitamin K antagonist (warfarin, acenocumarol), b. Unfractionated heparin, c. Low molecular weight heparin, or d. Inhibitors of coagulation factor IIa/Xa other than dabigatran, rivaroxaban or apixaban"}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 5. Whole blood, and/or blood clotting factors (such as: prothrombin complex concentrate [PCC], recombinant factor VIIa [rVIIa], fresh frozen plasma [FFP]) administered within 7 days before enrollment to the study."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 6. Anti-IIa/Xa activity (which is assumed to be directly proportional to the DOAC plasma concentration) is <50 ng/."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 7. Suspected subarachnoid haemorrhage based on specific symptomatology and/or physical examination (even if CT/MRI is normal)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 8. Any past (chronic) medical illnesses that significantly impairs patient’s functional status down to mRS 3 points or more (thus not only related to CNS pathologies and including cognitive impairment), and/or with a poor prognosis (e.g., neoplasms individually assessed to be of poor prognosis)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 9. Cerebral venous sinus thrombosis (CVST)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 10. Pulmonary embolism."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 11. Systemic or suspected cerebral vasculitis."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 12. Congenital or acquired coagulopathy presenting with: a. Prolonged aPTT above 30% of the upper limit of normal (local laboratory reference range), b. Increased INR ≥1.7"}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 13. Severe liver disease including acute hepatic failure, cirrhosis with/or without portal hypertension."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 14. Pregnancy."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 15. Predicted life expectancy <3 months."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 16. Participation in another clinical trial at the time of enrollment or planned inclusion in another clinical trial within less than 90 days of enrollment, provided that protocols of these trials interfere pathophysiologicaly or formally and administratively with the STROACT study."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 17. Previous participation in the current clinical trial."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 18. Advanced renal failure (eGFR <30 mL/min/1.73m2)."}
• {"criterion_text":"- OBSERVATIONAL PART OF THE STROACT STUDY: 19. Active infection with SARS-CoV-2 (up to 10 days from the first positive testing with any recommended assay or from the first symptoms of infection or severe “long” COVID-19 / severe Post-COVID Neurological Syndrome)."}

Primary endpoints

• {"endpoint_text":"- PRIMARY ENDPOINTS – INTERVENTIONAL PART OF THE STROACT STUDY: 1. The occurrence of thrombotic events and death (1- yes, 0-no).","definition_or_measurement_approach":"Occurrence of thrombotic events and death recorded as binary outcome (1 = yes, 0 = no); primary objective references incidence at 90 days."}
• {"endpoint_text":"- PRIMARY ENDPOINTS – OBSERVATIONAL PART OF THE STROACT STUDY: 1. Outcome in mRS at 90 days (the proportion of patients with AIS with excellent or good functional outcome assessed with modified Rankin scale (mRS), mRS 0-1 and 0-2 respectively) at 90 days (+/- 3 days) after the admission.","definition_or_measurement_approach":"Functional outcome assessed using the modified Rankin Scale at 90 days (+/-3 days); proportion achieving mRS 0-1 and mRS 0-2 reported."}

Secondary endpoints

• {"endpoint_text":"- SECONDARY END POINTS – ONLY INTERVENTIONAL PART OF THE STROACT STUDY: a) Efficacy: mRS at 90 days - the proportion of patients with AIS with excellent or good functional outcome assessed with modified Rankin scale (mRS).","definition_or_measurement_approach":"Modified Rankin Scale at 90 days; proportion with mRS 0-1 and 0-2."}
• {"endpoint_text":"- SECONDARY END POINTS – ONLY INTERVENTIONAL PART OF THE STROACT STUDY: b) Efficacy: Change in NIHSS score from baseline assessed at 7 (+/-1 day) after investigational treatment administration.","definition_or_measurement_approach":"Change in NIHSS from baseline to day 7 (+/-1 day)."}
• {"endpoint_text":"- Safety – only interventional part of the STROACT study: a) Incidence of deaths: - Deaths from any cause - Deaths subdivided by cause at 7 (+/-1 day), 30 (+/-2 days) and 90 days (+/ 3 days) after treatment administration.","definition_or_measurement_approach":"All-cause and cause-specific mortality assessed at 7, 30 and 90 days with specified windows."}
• {"endpoint_text":"- Safety – only interventional part of the STROACT study: b) Incidence of non-fatal events defined as - Recurrent ischaemic stroke - Haemorrhagic stroke (ICH or SAH) - Neurological deterioration (NIHSS) at 7 (+/-1 day) and 90 days (+/- 3 days) after treatment administration.","definition_or_measurement_approach":"Incidence of specified non-fatal events assessed at 7 and 90 days with NIHSS for neurological deterioration."}
• {"endpoint_text":"- Safety – only interventional part of the STROACT study: c) Rate and severity of early (symptomatic and asymptomatic) intracranial haemorrhage detected by neuroimaging: - CT or MRI at 24hrs (+/- 4hrs) after investigational treatment administration - CT or MRI at 7 days (+/- 1 day) after investigational treatment infusion and assessed according to European Cooperative Acute Stroke Study (ECASS II) classification.","definition_or_measurement_approach":"Intracranial haemorrhage detection by CT/MRI at 24h (+/-4h) and 7 days (+/-1d), classified per ECASS II."}
• {"endpoint_text":"- Safety – only interventional part of the STROACT study: d) Incidence and severity of major extracranial haemorrhages defined as: - fatal - severe enough to require transfusion or surgery - an absolute decrease in haemoglobin > 5 g/dL - a decrease in haematocrit of > 15% - leading to in persistent or temporary serious disability.","definition_or_measurement_approach":"Major extracranial bleeding events classified by severity criteria including transfusion/surgery, hemoglobin/hematocrit changes, fatality, and resulting disability."}
• {"endpoint_text":"- Safety – only interventional part of the STROACT study: e) Incidence and category of AEs reported during the study.","definition_or_measurement_approach":"Collection and categorisation of adverse events throughout study duration."}

Poland

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

07-03-2026

Processing Time Days

495

Number Of Sites

4

Number Of Participants

215

Primary sponsor

Full Name

Medical University Of Gdansk

Organisation Type

Educational Institution

Country Of Registered Address

Poland

Contract research organisations

Name

50Bio.Com Sp. z o.o.

Responsibilities

CRO

Third parties

• {"country":"Poland","full_name":"50Bio.Com Sp. z o.o.","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}