Acute ischemic stroke MedDRA version: 22.1 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Ondexxya
Product Name: Ondexxya
Pharmaceutical Form: Powder for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intr
Sponsors
MEDICAL UNIVERSITY OF GDANSK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Interventional Part: 1. Obtaining informed consent to participate in the trial prior to randomisation. 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. 2. Age =18 years. 3. Clinical diagnosis of acute ischemic stroke (sharply defined onset of first symptoms) resulting in a disabling neurological deficit. 4. Therapy 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. 5. Administration of study intervention (intravenous thrombolysis with alteplase or placebo) 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 patient had been randomised and there was an explicit clinical justification for delay in staring study intervention within 4.5h window, patient might continue in the study if rtPA (or rtPA placebo) could be administered within 6.0h from AIS onset. 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. Observational Part: 1. Age = 18 years. 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). 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. 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. 5. Obtaining the ICF to participate in the observational part of the STROACT study. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 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 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). 3. Mild and rapidly improving neurological deficit with high probability of complete recovery. 4. Clinically severe stroke with >18 points in NIHSS. 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. 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 Xa or IIa other than dabigatran, rivaroxaban, or apixaban 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. 8. Anti-Xa activity (which is assumed to be directly proportional to the NOAC plasma concentration) is 1/2 of the anatomical perfusion area of the middle cerebral artery (MCA), or anterior cerebral artery (ACA), or posterior cerebral artery (PCA). 10. Suspected subarachnoid haemorrhage based on specific symptomatology and/or physical examination (even if CT/MRI is normal). 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. 12. 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). NOTE: Patients after endovascular treatment of intracranial aneurysm may be considered for recruitment into the STROACT trial if the procedure was performed > 3 months prior to randomisation. 13. History of major surgery / trauma within 2 months before the current acute stroke. 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. 15. Recent (within 10 preceding days) traumatic external heart massage, obstetrical delivery, lumbar puncture, any puncture of a non-compressible blood vessel. 16. Recent (within 4 preceding weeks) myocardial infarction. 17. Severe trauma at the onset of acute ischemic stroke (e.g., skull fracture, long bone fracture, pelvic fracture). 18. Expected need for major surgery within 72 hours after randomisation (e.g., laparotomy, hip femoral/pelvic fracture surgery, endarterectomy). 19. Cerebral venous sinus thrombosis (CVST). 20. Pulmonary embolism. 21. Suspected infective endocarditis and/or pericarditis. 22. Acute pancreatitis. 23. Systemic or suspecte
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the efficacy of the investigational therapy in patients with acute ischaemic stroke on the non-vitamin K antagonist oral anticoagulants compared to placebo using modified Rankin Scale (mRS). 2. To assess the efficacy of the investigational therapy in patients with acute ischaemic stroke on the non-vitamin K antagonist oral anticoagulants compared to placebo using NIHSS score. 3. To assess the proportion of patients with AIS on active DOAC treatment without any intervention with excellent or good functional outcome in modified Rankin scale (mRS) - only observational part.;Secondary Objective: 1. To assess the efficacy of the investigational therapy in patients with acute ischaemic stroke on the non-vitamin K antagonist oral anticoagulants with pre-stroke functional status of 0-1 points in mRS compared to placebo using modified Rankin Scale (mRS). 2. To assess the incidence of fatal events after the investigational therapy in patients with acute ischaemic stroke on the non-vitamin K antagonist oral anticoagulants compared to placebo. 3. To assess the incidence of non-fatal events after the investigational therapy in patients with acute ischaemic stroke on the non-vitamin K antagonist oral anticoagulants compared to placebo.;Primary end point(s): Interventional part: 1. Transition from disabling (at admission) to non- disabling deficit (0-yes, 1-no). 2. Change in NIHSS between admission and 7-day follow-up. Observational part: 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.;Timepoint(s) of evaluation of this end point: 90 days (+/- 3 days) after study treatment administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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). 2. Incidence of deaths: - Deaths from any cause - Deaths subdivided by cause at 7 (+/-1 day), 30 (+/-2 days) and 90 days (+/- 3 days) after investigational treatment administration. 3. 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 investigational treatment administration.;Timepoint(s) of evaluation of this end point: 1.90 days (+/- 3 days) after investigational treatment administration. 2. 7 (+/-1 day) and 90 days (+/- 3 days) after investigational treatment administration. 3. 7 (+/-1 day), 30 (+/-2 days) and 90 days (+/- 3 days) aafter investigational treatment administration. 4.7 (+/-1 day), 30 (+/-2 days) and 90 days (+/- 3 days)after investigational treatment administration. | — |
Countries
Poland
Contacts
Public ContactTrial coordinator - B. Karaszewski
MEDICAL UNIVERSITY OF GDANSK
Outcome results
None listed