START: Imaging Guided Patient Selection for Interventional Revascularization Therapy

• Sponsor: Penumbra Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00963989
• Collaborator: (none)
• Enrollment: 146
• Location: 1
• Arm: 1
• Duration (Months): 84
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The primary objective of this clinical evaluation is to determine the safety and effectiveness of the Penumbra System in a stroke cohort who presents within 8 hours from symptom and with a known core infarct volume at admission. The secondary objective is to determine if there is a correlation between infarct volume and functional outcome in treated patients at 90 days post-procedure.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke	Device: Penumbra System	N/A

Detailed Description

Study Title: The START Trial: Clinical Outcome in Acute Stroke Treatment after Imaging Guided Patient Selection for Interventional Revascularization Therapy

Study Objective: The objective of this clinical evaluation is to determine the safety and effectiveness of the Penumbra System in a stroke cohort who presents within 8 hours from symptom onset and with a known core infarct volume at admission. The data will also be used to determine if there is a correlation between infarct volume and functional outcome at 90 days post-procedure. Safety is defined by the procedural serious adverse events, and effectiveness is defined by the rate of revascularization (TIMI 2-3/TICI 2a-3) and good functional outcome. Good functional outcome is defined by a modified Rankin scale (mRS) score of 2 or less at 90 days post-procedure. Core infarct volume at admission will be assessed by computed tomography perfusion (CTP), computed tomography angiography (CTA) or magnetic resonance DWI scans. The core infarct volumes will be sub-grouped by <50cc, 50-100cc and

100cc to determine the correlation with patient functional outcome.

Study Design: A prospective, single arm, multi-center trial. Up to 200 patients at up to 45 centers will be enrolled in the study. It is anticipated that up to 150 evaluable patients will be needed for analysis.

Patient Population: Patients presenting with symptoms of acute ischemic stroke within 8 hours from symptom onset and with a known imaging-defined infarct volume will be enrolled for interventional treatment by the Penumbra System to achieve revascularization of the target vessel territory.

Indication: The Penumbra System is intended for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset.

Sample Size Justification: Up to 200 subjects will be enrolled in order to obtain up to 150 evaluable patients. Assuming a post-procedure angiographic success (TIMI 2-3/TICI 2a-3) rate of 80% (120/150), the expected two-sided exact binomial 95% confidence interval is (72.7%, 86.1%). Assuming a 90-day mRS success (mRS 0-2) rate of 30%, the expected two-sided exact binomial 95% confidence interval is (22.8%, 38.0%). Additionally, the study results will be used for sample size estimates for a potential future randomized, concurrent controlled trial.

Core Laboratory and Clinical Event Committee An independent Core Lab will review and score all imaging scans for infarct volume, TIMI, TICI and ICH. A Clinical Event Committee will adjudicate all Serious Adverse Events for severity and causality (disease-, procedure-, drug-, or device-relatedness.

Study Rationale: Use of interventional revascularization techniques offer several potential clinical benefits by improving cerebral perfusion to the target vascular territory in certain patients. The validation of a simple, pragmatic, and executable image guided patient selection paradigm may identify a cohort of acute stroke patients who will benefit from interventional treatment by the Penumbra System and in whom revascularization as a treatment for acute stroke will be indicated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The START Trial: Clinical Outcome in Acute Stroke Treatment After Imaging Guided Patient Selection for Interventional Revascularization Therapy
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Penumbra Device Arm	Device: Penumbra System; The Penumbra System is used to revascularize clotted cerebral blood vessels.

Outcome Measures

Primary Outcome Measures

1. Functional Outcome as Defined by a mRS of 0-2 at 90 Days Post-procedure [At 90 days post-procedure]

   Modified Rankin Scale (mRS) ranges from 0 to 5, with higher scores being worse.

2. Angiographic Assessment of Vessel Patency as Measured by TIMI Score [At immediate post-procedure]

   Defined by Number of participants with Thrombolysis in Myocardial Infarction (TIMI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3.

3. Angiographic Assessment of Vessel Patency as Measured by Modified TICI Score [At immediate post-procedure]

   Defined by number of participants with modified thrombolysis in cerebral infarction (TICI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3.

4. Procedural Serious Adverse Events During the Procedure [During the procedure, approximately 24 hours]

   Defined by serious adverse events (SAEs) within 24 hours of the procedure

Secondary Outcome Measures

1. Good Neurological Recovery Post-procedure as Defined by a 10 Points or More Improvement on the NIHSS at Discharge [At Discharge, an average of 7 days]

2. Incidence of Symptomatic and Asymptomatic Hemorrhage Based on the ECASS Criteria and Patient Neurological Status Within 24 Hours of the Procedure [Within 24 hours of the procedure]

3. All Cause Mortality at 90 Days Post-procedure [At 90 days post-procedure]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• From 18 to 85 years of age.

• Evidence of proximal anterior circulation large vessel occlusion (TIMI /TICI 0-1) (Tables 2A & B). Target vessel occlusion may include the supra-clinoid segment of the ICA through the M1 segment of the MCA.

• Presented with symptoms consistent with acute ischemic stroke within 8 hours of symptom onset. Patients who presented within 3 hours must be ineligible or refractory to IV rtPA therapy.

• At time of enrollment, neurological deficit resulting in an NIH Stroke Scale (NIHSS) score of 10 or greater.

• Core infarct volume assessed by CTP, CTA or DWI scans within 60 minutes to arterial puncture.

• Signed informed consent.

Exclusion Criteria:

• History of stroke in the past 3 months.

• Vessel tortuosity too difficult to allow endovascular access.

• Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score of 1 or greater.

• Known severe allergy to contrast media.

• Uncontrolled hypertension (defined as systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg).

• Noncontrast CT evidence of the following conditions before enrollment:

• Significant mass effect with midline shift;

• Evidence of intracranial hemorrhage.

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

• Angiographic evidence of preexisting arterial injury.

• Life expectancy less than 90 days.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Penumbra Inc.

Investigators

• Study Director: Siu P Sit, PhD, Penumbra Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Penumbra Inc.
• ClinicalTrials.gov Identifier: NCT00963989
• Other Study ID Numbers: CLP 2480.A
• First Posted: Aug 24, 2009
• Last Update Posted: Nov 23, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Penumbra Inc.: Acute stroke; Large cerebral vessel occlusion; Core infarct volume; Penumbra System; Revascularization; Intracerebral hemorrhage; mRS; NIHSS; Procedural serious adverse events; All cause mortality
• Additional relevant MeSH terms: Stroke; Ischemic Stroke

Study Results

Participant Flow

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Period Title: Overall Study
STARTED	146
COMPLETED	127
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Overall Participants	146
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66 (14)
Sex: Female, Male (Count of Participants)
Female	82 56.2%
Male	64 43.8%
Baseline NIHSS (units on a scale) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [units on a scale]	19

Outcome Measures

1. Primary Outcome

Title	Functional Outcome as Defined by a mRS of 0-2 at 90 Days Post-procedure
Description	Modified Rankin Scale (mRS) ranges from 0 to 5, with higher scores being worse.
Time Frame	At 90 days post-procedure

Outcome Measure Data

Analysis Population Description

16 subjects with missing 90-day mRS assessment and 3 withdrew consent.

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	127
Count of Participants [Participants]	57 39%

2. Primary Outcome

Title	Angiographic Assessment of Vessel Patency as Measured by TIMI Score
Description	Defined by Number of participants with Thrombolysis in Myocardial Infarction (TIMI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3.
Time Frame	At immediate post-procedure

Outcome Measure Data

Analysis Population Description

One subject had two sites of occlusion

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	147
Count of Participants [Participants]	122 83.6%

3. Primary Outcome

Title	Angiographic Assessment of Vessel Patency as Measured by Modified TICI Score
Description	Defined by number of participants with modified thrombolysis in cerebral infarction (TICI) 2-3. A lower score means a worse outcome and higher scores means better outcome on a scale of 0-3.
Time Frame	At immediate post-procedure

Outcome Measure Data

Analysis Population Description

One subject had two sites of occlusion

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	147
Count of Participants [Participants]	122 83.6%

4. Primary Outcome

Title	Procedural Serious Adverse Events During the Procedure
Description	Defined by serious adverse events (SAEs) within 24 hours of the procedure
Time Frame	During the procedure, approximately 24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	146
Number [events]	40

5. Secondary Outcome

Title	Good Neurological Recovery Post-procedure as Defined by a 10 Points or More Improvement on the NIHSS at Discharge
Time Frame	At Discharge, an average of 7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	112
Count of Participants [Participants]	47 32.2%

6. Secondary Outcome

Title	Incidence of Symptomatic and Asymptomatic Hemorrhage Based on the ECASS Criteria and Patient Neurological Status Within 24 Hours of the Procedure
Time Frame	Within 24 hours of the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	146
Count of Participants [Participants]	18 12.3%

7. Secondary Outcome

Title	All Cause Mortality at 90 Days Post-procedure
Time Frame	At 90 days post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
Measure Participants	146
Count of Participants [Participants]	37 25.3%

Adverse Events

Arm/Group Title	Penumbra Device Arm
Arm/Group Description	Penumbra System: The Penumbra System is used to revascularize clotted cerebral blood vessels.
All Cause Mortality
	Penumbra Device Arm
	Affected / at Risk (%)	# Events
Total	37/146 (25.3%)
Serious Adverse Events
	Penumbra Device Arm
	Affected / at Risk (%)	# Events
Total	8/146 (5.5%)
Nervous system disorders
Carotid artery dissection	1/146 (0.7%)
Cerebral artery occlusion	1/146 (0.7%)
Cerebral haemorrhage	1/146 (0.7%)
Cerebral vasoconstriction	1/146 (0.7%)
Haemorrhagic transformation stroke	1/146 (0.7%)
Ischaemic cerebral infarction	1/146 (0.7%)
Vascular disorders
Vessel perforation	2/146 (1.4%)
Other (Not Including Serious) Adverse Events
	Penumbra Device Arm
	Affected / at Risk (%)	# Events
Total	14/146 (9.6%)
General disorders
Infusion site extravasation	1/146 (0.7%)
Nervous system disorders
Cerebral artery embolism	1/146 (0.7%)
Cerebral haematoma	1/146 (0.7%)
Cerebral haemorrhage	2/146 (1.4%)
Cerebral vasoconstriction	7/146 (4.8%)
Haemorrhagic transformation stroke	1/146 (0.7%)
Vascular dissection	1/146 (0.7%)

Limitations/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.