Ischemic Stroke
Conditions
Keywords
ischemic stroke, acute intervention, thrombolysis, rtPA, internal carotid artery, middle cerebral artery, mechanical thrombectomy, Penumbra System, clot length, mRS, NIHSS
Brief summary
The purpose of this trial is to assess the safety and effectiveness of the Penumbra System as an adjunctive treatment to intravenous (IV) recombinant human tissue plasminogen activator (rtPA)in patients with acute ischemic stroke from large vessel occlusion in the brain. IV rtPA is the only drug approved for the treatment of acute ischemic stroke but it does not work very well in cases where the stroke is caused by a large vessel occlusion. The hypothesis being tested is to determine if the addition of a treatment by a mechanical thrombectomy device like the Penumbra System can improve the clinical outcome of the patient over just using IV rtPA alone.
Detailed description
Current therapies for acute stroke are limited to the intravenous administration of a intravenous (IV) recombinant human tissue plasminogen activator (rtPA) for thrombolysis of the affected cerebral arteries within 3-4.5 hours from symptom onset, and the use of intra-arterial (IA) endovascular mechanical clot retrieval devices within 8 hours from ictus, all of which have limitations as mono therapies. For example, IV rtPA may not be very efficacious in large vessel occlusion and the long term effects of mechanical thrombectomy devices on patient functional outcome is unknown. This is a randomized, concurrent controlled study to assess the safety and effectiveness of the Penumbra System as adjunctive therapy to IV rtPA in the acute intervention of acute ischemic stroke. Patients presenting with symptoms of acute ischemic stroke who have evidence of a large clot burden (clot length \> 8mm) in the anterior circulation will be assigned to either IV rtPA therapy alone (0.9mg/kg to a maximum of 90mg) or a combined IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and intra-arterial (IA) adjunctive treatment with the Penumbra System. Each treated patient will be followed and assessed for 3 months after enrollment.
Interventions
0.9mg/kg to a maximum of 90mg
DEVICEPenumbra System
The Penumbra System is an aspiration based mechanical thrombectomy device
Sponsors
Penumbra Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. From 18 to 85 years of age 2. Present with symptoms consistent with an acute ischemic stroke and eligible for IV rtPA therapy (patients presenting 3-4.5 hrs from symptom onset are not eligible if they are \>80 yrs of age, have a history of stroke and diabetes, anticoagulant use (even if INR is \<1.7) and have a NIHSS score \>25 3. Evidence of a large vessel occlusion in the anterior circulation with a clot length of 8mm or longer 4. NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation 5. Signed informed consent
Exclusion criteria
1. History of stroke in the past 3 months. 2. Females who are pregnant 3. Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or greater 4. Known severe allergy to contrast media 5. Uncontrolled hypertension (defined as systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg) 6. CT evidence of the following conditions at randomization: * Significant mass effect with midline shift * Any acute ischemic changes in \>1/3 of the affected middle cerebral artery territory * Evidence of intracranial hemorrhage 7. Angiographic evidence of tantem extracranial occlusion or an arterial stenosis proximal to the occlusion that requires treatment prior to thrombus removal. Moderate stenosis not requiring treatment is not an exclusion 8. Angiographic evidence of preexisting arterial injury 9. Rapidly improving neurological status prior to randomization 10. Bilateral stroke 11. Intracranial tumors 12. Known history of cerebral aneurysm or arteriovenous malfunction 13. Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of \>1.7 14. Baseline platelets \<50,000 15. Use of IV heparin in the past 48 hours with PPT \>1.5 times the normalized ratio 16. Pre-treatment glucose \<50mg/dL or \>300mg/dL 17. Life expectancy less than 90 days prior to stroke onset 18. Participation in another clinical investigation that could confound the evaluation of the study device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Good Functional Outcome as Defined by a Modified Rankin Score of 0-2 | 90 days | The assessor is blinded to patient treatment assignment. |
| Incidence of All Serious Adverse Events | 90 days | A Serious Adverse Event is defined as an event that: 1. Led to death 2. Led to a serious deterioration in the health of the patient that: * Resulted in life-threatening illness or injury * Resulted in permanent impairment of a body structure or a body function * Required in-patient hospitalization or prolongation of existing hospitalization * Resulted in medical or surgical intervention to arrest permanent impairment to body structure or a body function * Led to fetal distress, fetal death or a congenital abnormality or birth defect |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Good Clinical Outcome | 30 days | Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIH stroke scale score at Discharge, a NIH stroke scale score of 0-1 at Discharge; or a 30-day modified Rankin scale score of 0-2 |
| Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage | 90 days | A symptomatic intracranial hemorrhage is defined as 24 hour CT evidence of an ECASS defined ICH and a 4-point or more worsening of the NIH Stroke Scale score |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV rtPA IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg
intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg | 53 |
| IV rtPA and IA Penumbra System Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System
Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device | 55 |
| Total | 108 |
Baseline characteristics
| Characteristic | IV rtPA | IV rtPA and IA Penumbra System | Total |
|---|---|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 10 | 67 years STANDARD_DEVIATION 11 | 68.7 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 30 Participants | 21 Participants | 51 Participants |
| Sex: Female, Male Male | 23 Participants | 34 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 62 | 42 / 43 |
| serious Total, serious adverse events | 32 / 62 | 20 / 43 |
Outcome results
Primary
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
The assessor is blinded to patient treatment assignment.
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV rtPA | Good Functional Outcome as Defined by a Modified Rankin Score of 0-2 | 14 Participants |
| IV rtPA and IA Penumbra System | Good Functional Outcome as Defined by a Modified Rankin Score of 0-2 | 19 Participants |
Primary
Incidence of All Serious Adverse Events
A Serious Adverse Event is defined as an event that: 1. Led to death 2. Led to a serious deterioration in the health of the patient that: * Resulted in life-threatening illness or injury * Resulted in permanent impairment of a body structure or a body function * Required in-patient hospitalization or prolongation of existing hospitalization * Resulted in medical or surgical intervention to arrest permanent impairment to body structure or a body function * Led to fetal distress, fetal death or a congenital abnormality or birth defect
Time frame: 90 days
Population: The number of participants here are taken from the as-treated population, where IV tPA alone is 62 which differs from the number of initial participants started based on participant flow. This is due to 9 subjects who were randomized to Penumbra System receiving IV tPA Alone and no Penumbra System was used.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV rtPA | Incidence of All Serious Adverse Events | 30 Participants |
| IV rtPA and IA Penumbra System | Incidence of All Serious Adverse Events | 18 Participants |
Secondary
Good Clinical Outcome
Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIH stroke scale score at Discharge, a NIH stroke scale score of 0-1 at Discharge; or a 30-day modified Rankin scale score of 0-2
Time frame: 30 days
Population: 30 day good clinical outcome based on ITT (intent-to-treat) population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV rtPA | Good Clinical Outcome | 17 Participants |
| IV rtPA and IA Penumbra System | Good Clinical Outcome | 24 Participants |
Secondary
Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage
A symptomatic intracranial hemorrhage is defined as 24 hour CT evidence of an ECASS defined ICH and a 4-point or more worsening of the NIH Stroke Scale score
Time frame: 90 days
Population: The number of participants here are taken from the as-treated population, where IV tPA alone is 62 which differs from the number of initial participants started based on participant flow. This is due to 9 subjects who were randomized to Penumbra System receiving IV tPA Alone and no Penumbra System was used.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV rtPA | Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage | 6 Participants |
| IV rtPA and IA Penumbra System | Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage | 4 Participants |