A Randomized, Concurrent Controlled Trial to Assess the Safety and Effectiveness of the Separator 3D as a Component of the Penumbra System in the Revascularization of Large Vessel Occlusion in Acute Ischemic Stroke

• ClinicalTrials.gov Identifier: NCT01584609
• Recruitment Status: Completed
• First Posted: April 25, 2012
• Results First Posted: September 13, 2018
• Last Update Posted: September 13, 2018
• Sponsor: Penumbra Inc.
• Information provided by (Responsible Party): Penumbra Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Acute Ischemic Stroke From Large Vessel Occlusion
• Interventions: Device: Penumbra System with Separator 3D; Device: Penumbra System alone
• Enrollment: 198

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Period Title: Overall Study
Started	98	100
Completed	86	96
Not Completed	12	4

Baseline Characteristics

Arm/Group Title		Penumbra System With Separator 3D	Penumbra System Alone	Total
Arm/Group Description		Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.	Total of all reporting groups
Overall Number of Baseline Participants		98	100	198
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	98 participants	100 participants	198 participants
		67.3 (13.6)	66.5 (12.5)	66.9 (13)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	98 participants	100 participants	198 participants
	Female	57 58.2%	54 54.0%	111 56.1%
	Male	41 41.8%	46 46.0%	87 43.9%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	98 participants	100 participants	198 participants
		98 100.0%	100 100.0%	198 100.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Angiographic Revascularization of the Occluded Target Vessel
Description	Number of Participants with Angiographic revascularization of the occluded target vessel defined by mTICI grade 2-3
Time Frame	At immediate post-procedure

Outcome Measure Data

Analysis Population Description

Analysis population demonstrate outcomes of number of subjects that met endpoint.

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	94	96
Measure Type: Count of Participants; Unit of Measure: Participants
	82 87.2%	79 82.3%

2. Primary Outcome

Title	Number of Device-related Serious Adverse Events
Description	[Not Specified]
Time Frame	Within 24 hours post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	98	100
Measure Type: Number; Unit of Measure: Device-Related Serious Adverse Events
	4	5

3. Primary Outcome

Title	Number of Procedure-related Serious Adverse Event
Description	[Not Specified]
Time Frame	Within 24 hours post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	98	100
Measure Type: Number; Unit of Measure: Procedure-related Serious Adverse Events
	10	14

4. Secondary Outcome

Title	Good Clinical Outcome at 30 Days
Description	Defined by a 10 points or more improvement in the NIHSS at Discharge, a NIHSS score of 0-1 at Discharge; or a 30-day mRS score of 0-2. The NIHSS is a stroke scale that measures impairment caused by stroke. The Modified Rankin scale (mRS) measures neurological disability or dependence for stroke patients.
Time Frame	30 days post-procedure

Outcome Measure Data

Analysis Population Description

Analysis population demonstrate outcomes of number of subjects that met endpoint.

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	97	100
Measure Type: Count of Participants; Unit of Measure: Participants
	58 59.8%	55 55.0%

5. Secondary Outcome

Title	Number of Participants With 90 Day mRS Score 0-2
Description	[Not Specified]
Time Frame	at 90 days post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	86	96
Measure Type: Count of Participants; Unit of Measure: Participants
	39 45.3%	44 45.8%

6. Secondary Outcome

Title	All Cause Mortality
Description	[Not Specified]
Time Frame	At 90 days post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	98	100
Measure Type: Count of Participants; Unit of Measure: Participants
	19 19.4%	26 26.0%

7. Secondary Outcome

Title	Number of Symptomatic Intracranial Hemorrhage
Description	[Not Specified]
Time Frame	Within 24 hours post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	98	100
Measure Type: Number; Unit of Measure: Symptomatic Intracranial Hemorrhage
	3	5

8. Secondary Outcome

Title	Good Neurological Outcome at 90 Days
Description	Defined by an mRS score of 0-2, or equal to the pre-stroke mRS score if the pre-stroke mRS score was higher than 2, or an improvement of 10 or more points on the NIHSS score
Time Frame	At 90 days post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra System With Separator 3D	Penumbra System Alone
Arm/Group Description:	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.	Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
Overall Number of Participants Analyzed	86	96
Measure Type: Count of Participants; Unit of Measure: Participants
	56 65.1%	55 57.3%

Adverse Events

Time Frame	Procedure up to 90 days
Adverse Event Reporting Description	Serious Adverse Events and Other (Not Including Serious): the total number of subjects analyzed is per protocol population. Data includes roll-in subjects and adjudicated by CEC. Events labeled as is in our Instructions for Use.
Arm/Group Title	Penumbra System With Separator 3D		Penumbra System Alone
Arm/Group Description	Penumbra System with Separator 3D: The Separator 3D is an additional Separator with a new tip configuration for the Penumbra System.		Penumbra System alone: The Penumbra System® is a new generation of neuro-embolectomy devices specifically designed to remove thrombus through aspiration.The treatment paradigm of this System involves the introduction of the Reperfusion Catheter through a guide catheter into the intracranial vasculature, and guided over an appropriate guidewire to the site of primary occlusion. The Reperfusion Catheter is used in parallel with the Separator and an aspiration source (Aspiration Pump) to separate the thrombus and aspirate it from the occluded vessel.
All-Cause Mortality
	Penumbra System With Separator 3D		Penumbra System Alone
	Affected / at Risk (%)		Affected / at Risk (%)
Total	19/98 (19.39%)		26/100 (26.00%)
Serious Adverse Events
	Penumbra System With Separator 3D		Penumbra System Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/88 (43.18%)		49/93 (52.69%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders †	2/88 (2.27%)	2	2/93 (2.15%)	2
Cardiac disorders
Cardiac disorders †	10/88 (11.36%)	10	7/93 (7.53%)	7
Endocrine disorders
Endocrine disorders †	0/88 (0.00%)	0	1/93 (1.08%)	1
Gastrointestinal disorders
Gastrointestinal disorders †	8/88 (9.09%)	8	10/93 (10.75%)
General disorders
General disorders and administration site conditions †	1/88 (1.14%)		0/93 (0.00%)
Immune system disorders
Immune system disorders †	0/88 (0.00%)	0	1/93 (1.08%)	1
Infections and infestations
Infections and infestations †	2/88 (2.27%)	2	6/93 (6.45%)	6
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications †	2/88 (2.27%)		2/93 (2.15%)
Investigations
Investigations †	0/88 (0.00%)	0	1/93 (1.08%)	1
Metabolism and nutrition disorders
Metabolism and nutrition disorders †	2/88 (2.27%)	2	1/93 (1.08%)	1
Nervous system disorders
Nervous system disorders †	19/88 (21.59%)	19	28/93 (30.11%)	28
Renal and urinary disorders
Renal and urinary disorders †	4/88 (4.55%)	4	1/93 (1.08%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic, and mediastinal disorders †	9/88 (10.23%)	9	11/93 (11.83%)	11
Vascular disorders
Vascular disorders †	1/88 (1.14%)	1	9/93 (9.68%)	9
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Penumbra System With Separator 3D		Penumbra System Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/88 (92.05%)		83/93 (89.25%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders †	24/88 (27.27%)	24	19/93 (20.43%)	19
Cardiac disorders
Cardiac Disorders †	28/88 (31.82%)	28	23/93 (24.73%)	23
Gastrointestinal disorders
Gastrointestinal Disorders †	21/88 (23.86%)	21	29/93 (31.18%)	29
General disorders
General disorders and administration site conditions †	25/88 (28.41%)	25	20/93 (21.51%)	20
Infections and infestations
Infections and Infestations †	28/88 (31.82%)	28	25/93 (26.88%)	25
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications †	10/88 (11.36%)	10	9/93 (9.68%)	9
Investigations
Investigations †	13/88 (14.77%)	13	6/93 (6.45%)	6
Metabolism and nutrition disorders
Metabolism and nutrition disorders †	27/88 (30.68%)	27	30/93 (32.26%)	30
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders †	9/88 (10.23%)	9	7/93 (7.53%)	7
Nervous system disorders
Nervous System Disorders †	48/88 (54.55%)	48	59/93 (63.44%)	59
Psychiatric disorders
Psychiatric disorders †	14/88 (15.91%)	14	19/93 (20.43%)	19
Renal and urinary disorders
Renal and urinary disorders †	14/88 (15.91%)	14	12/93 (12.90%)	12
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic, and mediastinal disorders †	23/88 (26.14%)	23	24/93 (25.81%)	24
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders †	8/88 (9.09%)	8	5/93 (5.38%)	5
Vascular disorders
Vascular Disorder †	27/88 (30.68%)	27	25/93 (26.88%)	25
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Michaella Corso
• Organization: Penumbra, Inc.
• Phone: (510) 748-3200
• EMail: mcorso@penumbrainc.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nogueira RG, Frei D, Kirmani JF, Zaidat O, Lopes D, Turk AS 3rd, Heck D, Mason B, Haussen DC, Levy EI, Mehta S, Lazzaro M, Chen M, Dorfler A, Yoo AJ, Derdeyn CP, Schwamm L, Langer D, Siddiqui A; Penumbra Separator 3D Investigators. Safety and Efficacy of a 3-Dimensional Stent Retriever With Aspiration-Based Thrombectomy vs Aspiration-Based Thrombectomy Alone in Acute Ischemic Stroke Intervention: A Randomized Clinical Trial. JAMA Neurol. 2018 Mar 1;75(3):304-311. doi: 10.1001/jamaneurol.2017.3967.

• Responsible Party: Penumbra Inc.
• ClinicalTrials.gov Identifier: NCT01584609
• Other Study ID Numbers: CLP 4853; CLP 4853 ( Other Identifier: Penumbrainc )
• First Submitted: April 23, 2012
• First Posted: April 25, 2012
• Results First Submitted: May 17, 2018
• Results First Posted: September 13, 2018
• Last Update Posted: September 13, 2018