Mechanical Retrieval and Recanalization of Stroke Clots U... | NCT00389467

ID	Type	Description	Link
NCT00389467	Registry Identifier	ClinicalTrials.gov

Status Module

Name	Class
National Institute of Neurological Disorders and Stroke (NINDS)	NIH

Description Module

Detailed Description

Stroke most commonly occurs when there is a blockage of blood flow to one of the arteries in the brain. The blockage is often caused by a clot. There is currently only one FDA-approved stroke treatment. However, only 2 percent of ischemic stroke patients receive this treatment because it must be given within 4.5 hours of the stroke onset. There is an overwhelming need for new treatments that extend the time window to treatment since most individuals with stroke arrive at the hospital after the 4.5-hour time window.

Two of the most promising new devices are the Merci Retriever, a tiny corkscrew device, and the Penumbra System, an aspiration device. Both are designed to remove clots from arteries and thereby restore blood flow to the brain.

The primary purpose of this study is to compare the effectiveness of treatment with the Merci Retriever or Penumbra System within 8 hours of symptom onset to standard medical treatment, and to identify people who might benefit from the devices by the appearance of the stroke on multimodal computerized tomography (CT) or magnetic resonance imaging (MRI). Previous testing has determined that the use of the Merci Retriever is successful in opening up blocked blood vessels in approximately ½ of the individuals in whom it is used, and the Penumbra System is successful in opening up blocked blood vessels in approximately 80% of the individuals in whom it is used.

A total of 120 participants from approximately 30 different medical centers will be enrolled into this study. Participants will be randomized to either receive treatment by mechanical embolectomy with the Merci Retriever or Penumbra System and standard medical care or treatment with standard medical care alone. Standard care for stroke patients may include intravenous fluid, careful regulation of blood pressure, blood-thinning medicine (such as heparin or warfarin), anti-platelet medicine (such as aspirin or clopidogrel), and rehabilitation therapies.

Participants undergoing the Merci Retriever or Penumbra System procedure will have a cerebral arteriogram with pictures taken with dye prior to the procedure to determine the location of the blockage, and following the procedure to determine if blood supply has been restored. The total mechanical embolectomy procedure with either device will take approximately 1 to 2 hours. Participants will have brief neurological exams several times during this time to monitor changes in their neurological condition.

Participants will have follow-up visits, including neurological exams, at 30 days and at 90 days.

This study is part of the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS), which allows researchers to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients in less than 2 hours, and finding ways to treat additional patients later.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1 Mechanical Embolectomy	Active Comparator	Participants will be randomized to receive mechanical embolectomy treatment either with the Merci Retriever or Penumbra System and standard medical care or treatment with standard medical care alone.	Device: Merci Retriever and Penumbra System
2	No Intervention	standard medical care

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Merci Retriever and Penumbra System	Device	The MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Retriever consists of a flexible, nickel titanium (nitinol) wire with a helical-shaped distal tip. The helical distal tip is covered with a platinum radiopaque coil, which facilitates fluoroscopic visualization. The body of the MERCI Retriever is covered with a hydrophilic coating that helps facilitate device placement. The MERCI Retriever is available in 6 configurations (Merci Retrievers X6, L5, L4, L6, V series, DAC). The Penumbra System uses a reperfusion catheter in parallel with a separator component and an aspiration source to achieve separation of the thrombus and subsequent aspiration of the occlusion from the vessel. The system is available in different sizes according to the target vessels (041 Reperfusion Catheter/Separator pair for use in vessels larger than 3mm, notably the ICA and M1; 032 Reperfusion Catheter/Separator pair for use in vessels 2mm - 3mm, notably the M2).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Modified Rankin Scale Score	Scale name is provided (Modified Rankin Scale) which is a standard measure of functional neurologic outcome in stroke. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.	at 90 days post-stroke

Secondary Outcomes

Measure	Description	Time Frame
Symptomatic Hemorrhagic Transformation	Symptomatic intracranial hemorrhage is defined as 4 point neurologic worsening on the National Institutes of Health Stroke Scale (NIHSS) score associated with parenchymal hematoma type 2 (PH-2), remote intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage on imaging. The NIHSS is a scale measuring specific neurologic deficits caused by a stroke with scores ranging from 0 to 42, and higher scores indicating more severe neurologic deficits. from the modified European Cooperative Acute Stroke Study (ECASS) II criteria

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

New focal disabling neurologic deficit consistent with acute cerebral ischemia (NIHSS >/= 6)
Age >/= 18 ≤ 85
Clot retrieval procedure can be initiated within 8 hours from onset
Large vessel proximal anterior circulation occlusion on MR or CT angiography (internal carotid, M1 or M2 MCA)
Pretreatment MRI performed according to MR RESCUE protocol
Signed informed consent obtained from the patient or patient's legally authorized representative
Premorbid modified Rankin score of 0-2
Allowed but not required: patients treated with IV tPA (tissue plasminogen activator) up to 4.5 hours from symptom onset with persistent target occlusion on post-treatment MR RESCUE MR or CT protocol performed at the completion of drug infusion (Note: Rapidly improving neurological signs prior to randomization is an exclusion)

Exclusion Criteria:

NIHSS >/= 30
Contraindication to MRI (pacemaker etc)
Acute intracranial hemorrhage
Coma
Rapidly improving neurological signs prior to randomization
Pre-existing medical, neurological or psychiatric disease that would confound the neurological, functional, or imaging evaluations
Pregnancy
Known allergy to iodine previously refractory to pretreatment medications
Current participation in another experimental treatment protocol
Contrast-Enhanced Neck MRA (magnetic resonance angiography) or CTA (computed tomography angiography) suggests proximal ICA occlusion, proximal carotid stenosis > 67%, or dissection
INR > 3.0 (international normalized ratio)
PTT > 3 x Normal (partial thromboplastin time)
Imaging data cannot be processed by the MR RESCUE computer
Renal Failure (serum creatinine > 2.0 or Glomerular Filtration Rate [GFR] < 30)

MRI Exclusion Criteria:

Contraindication to MRI (pacemaker, etc)

CT Exclusion Criteria:

Contraindication to iodinated contrast**

**Examples of possible iodinated contrast contraindications include:
Hyperthyroidism
History of severe allergic reaction to iodinated contrast material
History of sever kidney disease as an adult, including tumor or transplant surgery, or family history of kidney failure
Paraproteinemia syndromes or multiple myeloma
Collagen vascular disease
Severe cardiac insufficiency
Severely compromised liver function
Current therapy with metformin, aminoglycosides

Name	Affiliation	Role
Chelsea S Kidwell, MD	Professor of Neurology, Georgetown University	Principal Investigator
Reza Jahan, MD	Associate Professor of Radiology, UCLA Medical Center, Interventional Neuroradiology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California at Los Angeles, UCLA Stroke Network, 924 Westwood Blvd #300		Los Angeles	California	90024	United States

PubMed Identifier	Type	Citation	Retractions
28138001	Derived	Nael K, Knitter JR, Jahan R, Gornbein J, Ajani Z, Feng L, Meyer BC, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Liebeskind DS, Guzy J, Starkman S, Saver JL, Kidwell CS. Multiparametric Magnetic Resonance Imaging for Prediction of Parenchymal Hemorrhage in Acute Ischemic Stroke After Reperfusion Therapy. Stroke. 2017 Mar;48(3):664-670. doi: 10.1161/STROKEAHA.116.014343. Epub 2017 Jan 30.
23394476	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Embolectomy, Penumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less. Intra-arterial tPA up to 14 milligrams was allowed as rescue therapy within 6 hours of onset.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Modified Rankin Scale Score

Scale name is provided (Modified Rankin Scale) which is a standard measure of functional neurologic outcome in stroke. The scale runs from 0-6, running from perfect health without symptoms to death.

0 - No symptoms.
1 - No significant disability. Able to carry out all usual activities, despite some symptoms.
2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3 - Moderate disability. Requires some help, but able to walk unassisted.
4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6 - Dead.

Posted

Mean

95% Confidence Interval

units on a scale

at 90 days post-stroke

ID	Title	Description
OG000	Embolectomy, Penumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.
OG001	Standard Care, Penumbral	Standard medical care was recommended per the AHA (American Heart Association)/ASA (American Stroke Association) Guidelines for management of acute ischemic stroke. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.
OG002	Embolectomy, Nonpenumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A nonpenumbral pattern was defined as a predicted infarct core of greater than 90 ml or a proportion of predicted infarct tissue within the at-risk region of greater than 70%.
OG003	Standard Care, Nonpenumbral	Standard medical care was recommended per the AHA (American Heart Association)/ASA (American Stroke Association) Guidelines for management of acute ischemic stroke. A nonpenumbral pattern was defined as a predicted infarct core of greater than 90 ml or a proportion of predicted infarct tissue within the at-risk region of greater than 70%.

Units	Counts
Participants	OG00034 OG00134 OG00230 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003.9(3.3 to 4.4) OG0013.4(2.8 to 4.0) OG0024.0(3.4 to 4.6) OG003

Secondary

Symptomatic Hemorrhagic Transformation

Symptomatic intracranial hemorrhage is defined as 4 point neurologic worsening on the National Institutes of Health Stroke Scale (NIHSS) score associated with parenchymal hematoma type 2 (PH-2*), remote intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage on imaging. The NIHSS is a scale measuring specific neurologic deficits caused by a stroke with scores ranging from 0 to 42, and higher scores indicating more severe neurologic deficits.

*from the modified European Cooperative Acute Stroke Study (ECASS) II criteria

Posted

Number

participants

from baseline to day 7

ID	Title	Description
OG000	Embolectomy, Penumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.
OG001	Standard Care, Penumbral	Standard medical care was recommended per the AHA (American Heart Association)/ASA (American Stroke Association) Guidelines for management of acute ischemic stroke. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.

Secondary

Day 90 Mortality

Posted

Number

participants

at day 90

ID	Title	Description
OG000	Embolectomy, Penumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.
OG001	Standard Care, Penumbral	Standard medical care was recommended per the AHA (American Heart Association)/ASA (American Stroke Association) Guidelines for management of acute ischemic stroke. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.
OG002	Embolectomy, Nonpenumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A nonpenumbral pattern was defined as a predicted infarct core of greater than 90 ml or a proportion of predicted infarct tissue within the at-risk region of greater than 70%.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)
EG000	Total Cohort		74	118
EG001	Embolectomy, Penumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.	25	34
EG002	Standard Care, Penumbral	Standard medical care was recommended per the AHA (American Heart Association)/ASA (American Stroke Association) Guidelines for management of acute ischemic stroke. A favorable penumbral pattern was defined as a predicted infarct core of 90 ml or less and a proportion of predicted infarct tissue within the at-risk region of 70% or less.	15	34
EG003	Embolectomy, Nonpenumbral	Embolectomy patients were treated up to 8 hours from symptom onset with any combination of FDA-cleared embolectomy devices, including the Merci Retriever since trial initiation in 2004 and Penumbra System since 2009. A nonpenumbral pattern was defined as a predicted infarct core of greater than 90 ml or a proportion of predicted infarct tissue within the at-risk region of greater than 70%.	22	30
EG004	Standard Care, Nonpenumbral	Standard medical care was recommended per the AHA (American Heart Association)/ASA (American Stroke Association) Guidelines for management of acute ischemic stroke. A nonpenumbral pattern was defined as a predicted infarct core of greater than 90 ml or a proportion of predicted infarct tissue within the at-risk region of greater than 70%.	12	20

Serious Adverse Events

Term	Organ System	Statistical Information
Neurological worsening or cerebral edema	Nervous system disorders	EG00041 events39 affected118 at risk EG00111 events11 affected34 at risk EG0026 events6 affected34 at risk EG00317 events15 affected30 at risk EG0047 events7 affected20 at risk
Procedural Complications	Nervous system disorders	EG0007 events7 affected64 at risk EG0015 events5 affected34 at risk EG0020 events0 affected34 at risk EG003
Respiratory	Respiratory, thoracic and mediastinal disorders	EG00010 events9 affected118 at risk EG0012 events2 affected34 at risk EG0020 events0 affected34 at risk EG003
Cardiac	Cardiac disorders	EG00011 events9 affected118 at risk EG0015 events4 affected34 at risk EG0023 events2 affected34 at risk EG003
New Stroke	Nervous system disorders	EG0006 events6 affected118 at risk EG0014 events4 affected34 at risk EG0020 events0 affected34 at risk EG003
Infectious	Infections and infestations	EG0005 events5 affected118 at risk EG0011 events1 affected34 at risk EG0022 events2 affected34 at risk EG003
Symptomatic Hemorrhage	Nervous system disorders	EG0005 events5 affected118 at risk EG0011 events1 affected34 at risk EG0022 events2 affected34 at risk EG003
Gastrointestinal	Gastrointestinal disorders	EG0004 events3 affected118 at risk EG0010 events0 affected34 at risk EG0021 events1 affected34 at risk EG003
Renal	Renal and urinary disorders	EG0003 events3 affected118 at risk EG0010 events0 affected34 at risk EG0021 events1 affected34 at risk EG003
DVT	Vascular disorders	EG0002 events2 affected118 at risk EG0011 events1 affected34 at risk EG0020 events0 affected34 at risk EG003
Seizure	Nervous system disorders	EG0001 events1 affected118 at risk EG0011 events1 affected34 at risk EG0020 events0 affected34 at risk EG003
Heparin Induced Thrombocytopenia	Blood and lymphatic system disorders	EG0001 events1 affected118 at risk EG0010 events0 affected34 at risk EG0020 events0 affected34 at risk EG003
Psoas Hematoma	Musculoskeletal and connective tissue disorders	EG0001 events1 affected118 at risk EG0010 events0 affected34 at risk EG0020 events0 affected34 at risk EG003
Anemia	Blood and lymphatic system disorders	EG0001 events1 affected118 at risk EG0010 events0 affected34 at risk EG0020 events0 affected34 at risk EG003
Amputation	Surgical and medical procedures	EG0001 events1 affected118 at risk EG0010 events0 affected34 at risk EG0020 events0 affected34 at risk EG003
Death	General disorders	EG00024 events24 affected118 at risk EG0015 events5 affected34 at risk EG0027 events7 affected34 at risk EG003
Asymptomatic Hemorrhage	Nervous system disorders	EG0004 events4 affected118 at risk EG0013 events3 affected34 at risk EG0020 events0 affected34 at risk EG003

ID	Title	Description
BG000	Embolectomy, Penumbral	Treatment assignment = embolectomy, imaging pattern = penumbral
BG001	Standard Care, Penumbral	Treatment assignment = standard medical care, imaging pattern = penumbral
BG002	Embolectomy, Nonpenumbral	Treatment assignment = embolectomy, imaging pattern = nonpenumbral
BG003	Standard Care, Nonpenumbral	Treatment assignment = standard medical care, imaging pattern = nonpenumbral
BG004	Total	Total of all reporting groups

ID	Term
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D016769	Embolism and Thrombosis