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

Penumbra

Status and phase: Completed; Phase 4

Conditions: Ischemic Stroke

Treatments: Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA); Device: Penumbra System

Study type: Interventional

Funder types: Industry

Identifiers

NCT01429350

CLP 4338

Details and patient eligibility

About

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.

Full 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.

Enrollment: 108 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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108 participants in 2 patient groups

IV rtPA

Active Comparator group

Description:

IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg

Treatment:

Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA)

IV rtPA and IA Penumbra System

Experimental group

Description:

Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System

Treatment:

Device: Penumbra System