Back to resultsAssess the Penumbra System in the Treatment of Acute Stroke (THERAPY)
Primary Purpose
Ischemic Stroke
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
intravenous (IV) recombinant human tissue plasminogen activator (rtPA)
Penumbra System
Sponsored by
About this trial
This is an interventional treatment trial for Ischemic Stroke focused on measuring ischemic stroke, acute intervention, thrombolysis, rtPA, internal carotid artery, middle cerebral artery, mechanical thrombectomy, Penumbra System, clot length, mRS, NIHSS
Eligibility Criteria
Inclusion Criteria:
- From 18 to 85 years of age
- 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
- Evidence of a large vessel occlusion in the anterior circulation with a clot length of 8mm or longer
- NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation
- Signed informed consent
Exclusion Criteria:
- History of stroke in the past 3 months.
- Females who are pregnant
- Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or greater
- Known severe allergy to contrast media
- Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg)
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
- 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
- Angiographic evidence of preexisting arterial injury
- Rapidly improving neurological status prior to randomization
- Bilateral stroke
- Intracranial tumors
- Known history of cerebral aneurysm or arteriovenous malfunction
- Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7
- Baseline platelets <50,000
- Use of IV heparin in the past 48 hours with PPT >1.5 times the normalized ratio
- Pre-treatment glucose <50mg/dL or >300mg/dL
- Life expectancy less than 90 days prior to stroke onset
- Participation in another clinical investigation that could confound the evaluation of the study device
Sites / Locations
- Endovascular Surgical Neuroradiology, Swedish Medical Center
- Department of Neurological Surgery
- Neurosurgery, Rush University Medical Center
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
IV rtPA
IV rtPA and IA Penumbra System
Arm Description
IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg
Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System
Outcomes
Primary Outcome Measures
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
The assessor is blinded to patient treatment assignment.
Incidence of All Serious Adverse Events
A Serious Adverse Event is defined as an event that:
Led to death
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 Outcome Measures
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01429350
Brief Title
Assess the Penumbra System in the Treatment of Acute Stroke
Acronym
THERAPY
Official Title
The THERAPY Trial: The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Penumbra Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
ischemic stroke, acute intervention, thrombolysis, rtPA, internal carotid artery, middle cerebral artery, mechanical thrombectomy, Penumbra System, clot length, mRS, NIHSS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
108 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IV rtPA
Arm Type
Active Comparator
Arm Description
IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg
Arm Title
IV rtPA and IA Penumbra System
Arm Type
Experimental
Arm Description
Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System
Intervention Type
Drug
Intervention Name(s)
intravenous (IV) recombinant human tissue plasminogen activator (rtPA)
Other Intervention Name(s)
recombinant tissue plasminogen activator, Alteplase
Intervention Description
0.9mg/kg to a maximum of 90mg
Intervention Type
Device
Intervention Name(s)
Penumbra System
Intervention Description
The Penumbra System is an aspiration based mechanical thrombectomy device
Primary Outcome Measure Information:
Title
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
Description
The assessor is blinded to patient treatment assignment.
Time Frame
90 days
Title
Incidence of All Serious Adverse Events
Description
A Serious Adverse Event is defined as an event that:
Led to death
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
Secondary Outcome Measure Information:
Title
Good Clinical Outcome
Description
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
Title
Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
From 18 to 85 years of age
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
Evidence of a large vessel occlusion in the anterior circulation with a clot length of 8mm or longer
NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation
Signed informed consent
Exclusion Criteria:
History of stroke in the past 3 months.
Females who are pregnant
Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or greater
Known severe allergy to contrast media
Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg)
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
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
Angiographic evidence of preexisting arterial injury
Rapidly improving neurological status prior to randomization
Bilateral stroke
Intracranial tumors
Known history of cerebral aneurysm or arteriovenous malfunction
Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7
Baseline platelets <50,000
Use of IV heparin in the past 48 hours with PPT >1.5 times the normalized ratio
Pre-treatment glucose <50mg/dL or >300mg/dL
Life expectancy less than 90 days prior to stroke onset
Participation in another clinical investigation that could confound the evaluation of the study device
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J Mocco, MD, MS
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pooja Khatri, MD
Organizational Affiliation
Department of Neurology, University of Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Osama Zaidat, MD, MSc
Organizational Affiliation
Neurointerventional Program, Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Endovascular Surgical Neuroradiology, Swedish Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Department of Neurological Surgery
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Neurosurgery, Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28596447
Citation
Yoo AJ, Khatri P, Mocco J, Zaidat OO, Gupta R, Frei D, Lopes D, Shownkeen H, Berkhemer OA, Meyer D, Hak SS, Kuo SS, Buell H, Bose A, Sit SP, von Kummer R; THERAPY Trial Investigators. Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial. Stroke. 2017 Jul;48(7):1895-1900. doi: 10.1161/STROKEAHA.116.016253. Epub 2017 Jun 8.
Results Reference
derived
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Assess the Penumbra System in the Treatment of Acute Stroke
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