Acute Ischemic Stroke (AIS) MedDRA version: 9.1 Level: LLT Classification code 10055221 Term: Ischemic stroke
Conditions
Sponsors
Nuvelo, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria will be eligible for this study: a. Clinical diagnosis of AIS defined as the sudden onset of an acute focal neurological deficit presumed to be due to cerebral ischemia b. Arterial occlusion of the carotid T or a M1, M2, or M1-M2 branch of the middle cerebral artery (MCA) as documented by CT angiography or magnetic resonance angiography c. Arteriographically confirmed occlusion of the carotid T or a M1, M2, or M1-M2 branch of the MCA d. The subject (or legally acceptable representative) must give written informed consent e. Age 18 years to 85 years f. Onset of symptoms of AIS (i.e., last known well time) within 3-9 hours g. Baseline NIHSS of 4 to 25 h. Available for follow-up assessments at 30 and 90 days 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria are not eligible for the study. a. Contraindication to systemic anticoagulation, e.g., history of documented hemorrhage requiring treatment within the past 30 days; history of a hereditary bleeding disorder or known bleeding diathesis; major surgery or trauma, open chest massage, ocular surgery or hemorrhagic retinopathy within the past 30 days; puncture at non-compressible site within 48 hours prior to administration of study drug; history of stroke (excluding the index event), unstable central nervous system structural abnormalities (e.g., arteriovenous malformation or brain tumor) within the past 3 months, and any history of prior intracranial hemorrhage b. Uncontrolled hypertension at study entry as defined by systolic blood pressure (SBP) greater than 180 mmHg or diastolic blood pressure (DBP) greater than or equal to 100 mmHg on repeated measures prior to study entry despite the use of IV antihypertensive agents c. Expectation based on timing of presentation that alfimeprase administration will not be able to be completed by 9 hours after stroke onset d. Inability to initiate alfimeprase dosing within 120 minutes of the qualifying imaging scan e. Coma f. Rapidly improving neurological symptoms at the time of screening g. Brain CT or MRI evidence of intracranial bleeding of any age h. High clinical suspicion for subarachnoid hemorrhage despite a negative baseline CT or MRI i. CT evidence of an acute and/or evolving hypodensity greater than 1/3 of the MCA territory in the vascular territory to be treated or Alberta Stroke Program Early CT Score (ASPECTS) of less than or equal to 5 j. MRI diffusion weighted imaging lesion greater than 1/3 of the MCA territory in the vascular distribution to be treated k. Carotid artery and/or intracranial artery stenosis that precludes safe passage of a microcatheter to treat the primary AOL l. Life expectancy of less than 6 months (e.g., terminal cancer) m. History of significant acute or chronic kidney disease, including known nephrotic syndrome, that would preclude safe contrast angiography n. Known allergy to contrast agents o. History of immune deficiency p. History of heparin-induced thrombocytopenia (HIT) q. Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to enrollment (Stage I) / randomization (Stage II) r. Any stroke, myocardial infarction, or use of thrombolytic therapy (including investigational thrombolytic therapy) within 3 months prior to enrollment (Stage I) / randomization (Stage II) s. Past participation in any alfimeprase clinical trial t. Pregnant, lactating, or actively menstruating women and women of child-bearing potential who are not using adequate contraceptive precautions (e.g., intrauterine device, oral contraceptives, barrier methods, or other contraception deemed adequate by the investigator) u. Current use of oral anticoagulants or an international normalized ratio (INR) greater than 1.4 v. Any non-atherosclerotic arteriopathy (e.g., vasculitis) w. Any prior neurologic event that would obscure the radiographic or clinical evaluation of the new index neurologic deficits x. Subjects with known renal insufficiency defined as a serum creatinine > 2 mg/dL (> 180 µmol/L) y. Subjects with known clinically significant hepatic disease defined as transaminase values > 3x ULN z. Subjects with any malignant neoplasm diagnosed within five years prior to screening, with t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PRIMARY SAFETY OBJECTIVE: To evaluate the safety of intra-arterial catheter-directed bolus alfimeprase as measured by symptomatic intracerebral hemorrhage (ICH) rate up to 24-30 hours after initiation of alfimeprase dosing PRIMARY EFFICACY OBJECTIVE: To evaluate the technical efficacy of intra-arterial catheter-directed bolus alfimeprase as measured by recanalization of the primary arterial occlusive lesion (AOL) at 120 minutes after initiation of alfimeprase dosing OR recanalization of the primary AOL at 60 minutes after initiation of alfimeprase dosing if TIMI Grade 3 flow is achieved and the underlying cerebral vessel is normal angiographically. ;Secondary Objective: SECONDARY OBJECTIVES: To evaluate safety: • Relative hypotension requiring treatment (i.e., volume expanders and/or vasopressors) • New cardiac events (e.g., cardiac ischemia, congestive heart failure, and dysrhythmia) • Relative hypotension not requiring treatment • Asymptomatic ICH up to 24 hours after initiation of alfimeprase dosing • New AIS up to 24 hours after initiation of alfimeprase dosing • New AIS up to 7 days after initiation of alfimeprase dosing • Major bleeding events up to 30 days after alfimeprase dosing • Adverse events (AEs) and serious adverse events (SAEs) up to 30 days after alfimeprase dosing • Mortality up to 30 and 90 days after alfimeprase dosing For the secondary objectives to evaluate Efficacy: Please refer to the HA009 study Protocol p.34 ;Primary end point(s): PRIMARY SAFETY ENDPOINT: • Rate of symptomatic ICH at 24 hours (based on CT performed up to 24-30 hours after initiation of alfimeprase dosing) PRIMARY EFFICACY ENDPOINT: • Rate of recanalization of the primary AOL at 120 minutes after initiation of alfimeprase dosing OR recanalization of the primary AOL at 60 minutes after initiation of alfimeprase dosing if TIMI Grade 3 flow is achieved and the underlying cerebral vessel is normal angiographically SECONDARY SAFETY ENDPOINTS: • Rate of relative | — |
Countries
Austria
Outcome results
None listed