Assess the Penumbra System in the Treatment of Acute Stroke (THERAPY)

The THERAPY Trial: The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA); Device: Penumbra System

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80112
      • Endovascular Surgical Neuroradiology, Swedish Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • Department of Neurological Surgery
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Neurosurgery, Rush University Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IV rtPA; IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg	Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA); 0.9mg/kg to a maximum of 90mg; Other Names: recombinant tissue plasminogen activator, Alteplase
Experimental: 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	Device: Penumbra System; The Penumbra System is an aspiration based mechanical thrombectomy device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2	The assessor is blinded to patient treatment assignment.	90 days
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 injuryResulted in permanent impairment of a body structure or a body functionRequired in-patient hospitalization or prolongation of existing hospitalizationResulted in medical or surgical intervention to arrest permanent impairment to body structure or a body functionLed to fetal distress, fetal death or a congenital abnormality or birth defect	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	30 days
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	90 days

Collaborators and Investigators

• Sponsor: Penumbra Inc.
• Investigators: Principal Investigator: J Mocco, MD, MS, Vanderbilt University Medical Center; Principal Investigator: Pooja Khatri, MD, Department of Neurology, University of Cincinnati; Principal Investigator: Osama Zaidat, MD, MSc, Neurointerventional Program, Medical College of Wisconsin

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 2, 2011
• First Submitted That Met QC Criteria: September 6, 2011
• First Posted (Estimate): September 7, 2011

Study Record Updates

• Last Update Posted (Actual): September 22, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: thrombolysis; middle cerebral artery; ischemic stroke; mechanical thrombectomy; NIHSS; Penumbra System; mRS; acute intervention; rtPA; internal carotid artery; clot length
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: CLP 4338