Clinical trial NCT01429350: Assess the Penumbra System in the Treatment of Acute Stroke
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ischemic Stroke
Keywords: ischemic stroke
acute intervention
thrombolysis
rtPA
internal carotid artery
middle cerebral artery
mechanical thrombectomy
Penumbra System
clot length
mRS
NIHSS
Lead sponsor: Penumbra Inc.
Sponsor class: INDUSTRY
First posted: 2011-09-07
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
timeFrame: 90 days
measure: Incidence of All Serious Adverse Events
timeFrame: 90 days
Secondary outcomes:
measure: Good Clinical Outcome
timeFrame: 30 days
measure: Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage
timeFrame: 90 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: Endovascular Surgical Neuroradiology, Swedish Medical Center
state: Colorado
city: Gainesville
country: United States
facility: Department of Neurological Surgery
state: Florida
city: Chicago
country: United States
facility: Neurosurgery, Rush University Medical Center
state: Illinois
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Vanderbilt University Medical Center
name: J Mocco, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurology, University of Cincinnati
name: Pooja Khatri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurointerventional Program, Medical College of Wisconsin
name: Osama Zaidat, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
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.