Study to Assess the Safety and Effectiveness of the Penumbra System

• Sponsor: Penumbra Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00334061
• Collaborator: (none)
• Enrollment: 125
• Location: 1
• Duration (Months): 17
• Patients Per Site Per Month: 7.3

Study Details

Study Description

Brief Summary

This clinical evaluation is a prospective, single-arm, multi-center trial.

The purpose of this clinical evaluation is to assess the safety and effectiveness of the Penumbra System in the revascularization of patients presenting with acute ischemic stroke secondary to intracranial, large vessel, occlusive disease.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: Penumbra System	Phase 2

Detailed Description

Purpose:

The purpose of this clinical evaluation is to assess the safety and effectiveness of the Penumbra System in the revascularization of patients presenting with acute ischemic stroke secondary to intracranial, large vessel, occlusive disease. Up to 125 evaluable patients will be enrolled in the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Penumbra™ Stroke System in the Revascularization of Patients With Acute Ischemic Stroke Secondary to Intracranial Large Vessel Occlusive Disease
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jun 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Revascularization of the Occluded Target Vessel [3-Month Post-Procedure]

   Revascularization is defined by a Thrombolysis in Myocardial Infarction (TIMI) score of 2 or 3 following use of the Penumbra System. TIMI scores are used to describe blood flow at the treated vessel with 0 designating no flow and 3 for normal flow.

2. Percentage of Participants With Device-related and Procedure-related Serious Adverse Events [3-Month Post-Procedure]

Secondary Outcome Measures

1. Percentage of Participants With Either a 4-point Improvement on the National Institutes of Health Stroke Scale (NIHSS) at Discharge or a Modified Rankin Scale (mRS) Score of ≤ 2 at 30 Days After Treatment [Discharge or 30-Days Post-Procedure]

   NIHSS is a 42 point scale to describe the neurological status of the patients: 0=no stroke; 1-15=minor to moderate stroke; 15-20=moderate/severe stroke; 21-42=severe stroke. The mRS is a scale to determine the activities of daily living of the patient with a score of 0 designating normal activities to a score of 6 designating death.

2. Percentage of Participants With a Modified Rankin Scale (mRS) Score of ≤ 2 at 90 Days Post Treatment [90-Day]

   The mRS is a scale to determine the activities of daily living of the patient with a score of 0 designating normal activities to a score of 6 designating death.

3. Percentage of Participants With All Cause Mortality [90-Days Post-Treatment]

4. Percentage of Participants With Symptomatic Hemorrhage [24-Hour Post-Procedure]

   All treated patients were scanned by computed tomography (CT) at 24-hours post-procedure to detect the presence of intracranial hemorrhage.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical signs consistent with acute ischemic stroke

• 18 to 79 years of age

• Neurological deficit resulting in an NIH Stroke Scale (NIHSS) score > 8

• TIMI 0 or TIMI I flow in vessels accessible to the Penumbra System

• Signed informed consent

• Present within 8 hours of stroke symptom onset; ineligible or refractory to intravenous tissue plasminogen activator (t-PA) therapy if presenting within 3 hours of symptom onset.

Exclusion Criteria:

• Evidence of rapidly improving neurological signs of stroke at time of enrollment

• NIHSS > 30 or coma

• Females who are pregnant

• Vessel tortuosity too difficult to allow endovascular access

• Known hemorrhagic diathesis, coagulation deficiency, or on oral anticoagulant therapy with an International Normalized Ratio (INR) > 3.0

• Partial thromboplastin time (PTT) greater than 2 times the lab normal

• Admission platelets < 30,000

• Pre-existing neurological or psychiatric disease that could confound the study results

• Known severe allergy to contrast media

• Uncontrolled hypertension

• Computed tomography (CT) evidence of significant mass effect with a midline shift

• CT reveals evidence of large hypodensity region > 1/3 of the middle cerebral artery territory

• CT reveals evidence of intracranial hemorrhage

• CT reveals significant mass effect with midline shift

• Angiographic evidence of an arterial stenosis proximal to the occlusion that could prevent thrombus removal

• Angiographic evidence of preexisting arterial injury

• Life expectancy of less than 90 days

• Participation in another clinical investigation that could confound the evaluation of the study device.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Luke's Hospital	Kansas City	Missouri	United States	64111

Sponsors and Collaborators

• Penumbra Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00334061
• Other Study ID Numbers: CLP 0676
• First Posted: Jun 6, 2006
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by , ,: Penumbra; Ischemic; Stroke; Intervention; Neurovascular; Thrombus; Embolectomy; Ischemic stroke
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Recruitment Details	From June 19, 2006 to June 5, 2007 a total of 856 patients were screened of which 125 patients were enrolled at 24 centers in Europe and the United States.

Arm/Group Title	Penumbra System
Arm/Group Description
Period Title: Overall Study
STARTED	125
COMPLETED	125
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Penumbra System
Arm/Group Description
Overall Participants	125
Age (Count of Participants)
<=18 years	1 0.8%
Between 18 and 65 years	53 42.4%
>=65 years	71 56.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (13.5)
Sex: Female, Male (Count of Participants)
Female	61 48.8%
Male	64 51.2%
Region of Enrollment (participants) [Number]
United States	76 60.8%
Europe	49 39.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Revascularization of the Occluded Target Vessel
Description	Revascularization is defined by a Thrombolysis in Myocardial Infarction (TIMI) score of 2 or 3 following use of the Penumbra System. TIMI scores are used to describe blood flow at the treated vessel with 0 designating no flow and 3 for normal flow.
Time Frame	3-Month Post-Procedure

Outcome Measure Data

Analysis Population Description

Intention to Treat

Arm/Group Title	Penumbra System
Arm/Group Description
Measure Participants	125
Number [Percentage of Participants]	81.2 65%

2. Primary Outcome

Title	Percentage of Participants With Device-related and Procedure-related Serious Adverse Events
Time Frame	3-Month Post-Procedure

Outcome Measure Data

Analysis Population Description

All adverse events were summarized by showing the number and percent of patients who reported the event. Events were also reported by relationship to the procedure or device. Causality of adverse events was adjudicated by a Clinical Events Committee. The denominator for the analyses was all enrolled patients.

Arm/Group Title	Penumbra System
Arm/Group Description
Measure Participants	125
Number [Percentage of Participants]	2.4 1.9%

3. Secondary Outcome

Title	Percentage of Participants With Either a 4-point Improvement on the National Institutes of Health Stroke Scale (NIHSS) at Discharge or a Modified Rankin Scale (mRS) Score of ≤ 2 at 30 Days After Treatment
Description	NIHSS is a 42 point scale to describe the neurological status of the patients: 0=no stroke; 1-15=minor to moderate stroke; 15-20=moderate/severe stroke; 21-42=severe stroke. The mRS is a scale to determine the activities of daily living of the patient with a score of 0 designating normal activities to a score of 6 designating death.
Time Frame	Discharge or 30-Days Post-Procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System
Arm/Group Description
Measure Participants	125
Number [Percentage of Participants]	41.6 33.3%

4. Secondary Outcome

Title	Percentage of Participants With a Modified Rankin Scale (mRS) Score of ≤ 2 at 90 Days Post Treatment
Description	The mRS is a scale to determine the activities of daily living of the patient with a score of 0 designating normal activities to a score of 6 designating death.
Time Frame	90-Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System
Arm/Group Description
Measure Participants	125
Number [Percentage of Participants]	25 20%

5. Secondary Outcome

Title	Percentage of Participants With All Cause Mortality
Time Frame	90-Days Post-Treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System
Arm/Group Description
Measure Participants	125
Number [Percentage of Participants]	32.8 26.2%

6. Secondary Outcome

Title	Percentage of Participants With Symptomatic Hemorrhage
Description	All treated patients were scanned by computed tomography (CT) at 24-hours post-procedure to detect the presence of intracranial hemorrhage.
Time Frame	24-Hour Post-Procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System
Arm/Group Description
Measure Participants	125
Number [Percentage of Participants]	11.2 9%

Adverse Events

Arm/Group Title	Penumbra System
Arm/Group Description
All Cause Mortality
	Penumbra System
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Penumbra System
	Affected / at Risk (%)	# Events
Total	65/125 (52%)
Cardiac disorders
Cardiac Arrhythmia	4/125 (3.2%)
Myocardial Infarction	3/125 (2.4%)
General disorders
Infection	7/125 (5.6%)
Nervous system disorders
Cerebral Edema	14/125 (11.2%)
Intracerebral Hemorrhage	10/125 (8%)
Worsening Symptoms of Qualifying Stroke	9/125 (7.2%)
Stroke in New Territory	3/125 (2.4%)
Renal and urinary disorders
Renal Dysfunction/Failure	3/125 (2.4%)
Respiratory, thoracic and mediastinal disorders
Respiratory Dysfunction/Failure	10/125 (8%)
Other Pulmonary Complications	7/125 (5.6%)
Pneumonia	5/125 (4%)
Skin and subcutaneous tissue disorders
Access Site Complication	3/125 (2.4%)
Vascular disorders
Peripheral Vascular Complication	3/125 (2.4%)
Other (Not Including Serious) Adverse Events
	Penumbra System
	Affected / at Risk (%)	# Events
Total	125/125 (100%)
Blood and lymphatic system disorders
Anemia	13/125 (10.4%)
Coagulopathy	5/125 (4%)
Cardiac disorders
Cardiac Arrhythmia	13/125 (10.4%)
Cardiac Complications	3/125 (2.4%)
Gastrointestinal disorders
Nausea	9/125 (7.2%)
Constipation	7/125 (5.6%)
Diarrhea	2/125 (1.6%)
GERD	2/125 (1.6%)
General disorders
Pain	21/125 (16.8%)
Fever	14/125 (11.2%)
Ulcer	2/125 (1.6%)
Other	16/125 (12.8%)
Hepatobiliary disorders
Hyperglycemia	10/125 (8%)
Hepato-Biliary Dysfunction	5/125 (4%)
Infections and infestations
Infection	31/125 (24.8%)
Pneumonia	23/125 (18.4%)
Injury, poisoning and procedural complications
Cerebral Edema	12/125 (9.6%)
Metabolism and nutrition disorders
Electrolyte Imbalance	22/125 (17.6%)
Peripheral Edema	5/125 (4%)
Nervous system disorders
Headache	8/125 (6.4%)
Worsening Symptoms of Qualifying Stroke	5/125 (4%)
Seizure	2/125 (1.6%)
Psychiatric disorders
Depression	5/125 (4%)
Dysphasia-Aspiration	4/125 (3.2%)
Anxiety	3/125 (2.4%)
Confusion	3/125 (2.4%)
Renal and urinary disorders
Renal Dysfunction/Failure	7/125 (5.6%)
Respiratory, thoracic and mediastinal disorders
Other Pulmonary Complications	12/125 (9.6%)
Vascular disorders
Hypotension	9/125 (7.2%)
Peripheral Vascular Complication	8/125 (6.4%)
Hypertension	4/125 (3.2%)
Peripheral Hemorrhage	4/125 (3.2%)
Embolization of Previously Uninvolved Vessel	2/125 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.