Ischemic Stroke
Conditions
Keywords
Mechanical thrombectomy, Acute ischemic stroke, Wake up stroke, Late presenting stroke
Brief summary
The purpose of the study is to evaluate the hypothesis that Trevo thrombectomy plus medical management leads to superior clinical outcomes at 90 days as compared to medical management alone in appropriately selected subjects experiencing an acute ischemic stroke when treatment is initiated within 6-24 hours after last seen well.
Detailed description
The study is a prospective, randomized, multi-center, Phase II/III (feasibility/pivotal), adaptive, controlled trial, designed to demonstrate that mechanical thrombectomy using the Trevo Retriever with medical management is superior to medical management alone in improving clinical outcomes at 90 days in appropriately selected wake up and late presenting acute ischemic stroke subjects. The intent of this study is to support the use of the Trevo Retriever beyond the currently labeled 8 hour indicated time limit in wake up, unclear onset, and late presenting ischemic stroke subjects, who currently have no other option besides medical management of their symptoms. Patients with wake-up strokes, strokes with unclear onset time, and witnessed late presenting strokes may potentially benefit from intra-arterial reperfusion therapy. However, an important indicator of whether subjects will benefit or not during this later time window is the confirmation of a large vessel occlusion (LVO), and assessment of the core infarct volume relative to the volume of salvageable penumbra. Therefore, standardized imaging selection of subjects is required for inclusion into the study. This trial has been designed with subject safety in mind, as a seamless Phase II (feasibility) / Phase III (pivotal) adaptive design, in order to address the concerns around potential unknown harms to enrolled subjects. This study will help to answer the question of whether carefully selecting subjects by using Clinical Imaging Mismatch will allow acute ischemic stroke patients who present at or beyond 6 hours from Time Last Seen Well (TLSW) to be considered for intra-arterial intervention. If Trevo thrombectomy plus medical management leads to better clinical outcomes over medical management alone, more patients in the future could receive endovascular treatment (either in addition to or in lieu of IV tPA).
Interventions
DEVICETrevo Thrombectomy Procedure
stent retriever; intended to restore blood flow in the neurovasculature by removing thrombus (clot)
OTHERMedical Management
Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc
Sponsors
Stryker Neurovascular
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: 1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups: 1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration) 2. Subject is contraindicated for IV t-PA administration 2. Age ≥18 3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume) 4. Subject can be randomized between with 6 to 24 hours after time last known well 5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1) 6. Anticipated life expectancy of at least 6 months 7. Subject willing/able to return for protocol required follow up visits 8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form\* * If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.) Imaging Inclusion Criteria: 1. \< 1/3 MCA territory involved, as evidenced by CT or MRI 2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA 3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps: 1. 0-\<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old) 2. 0-\<31 cc core infarct and NIHSS ≥ 10 (and age \< 80 years old) 3. 31 cc to \<51 cc core infarct and NIHSS ≥ 20 (and age \< 80 years old) General
Exclusion criteria
1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history 2. Rapid improvement in neurological status to an NIHSS \<10 or evidence of vessel recanalization prior to randomization 3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept) 4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment 5. Baseline blood glucose of \<50mg/dL (2.78 mmol) or \>400mg/dL (22.20 mmol) 6. Baseline hemoglobin counts of \<7 mmol/L 7. Baseline platelet count \< 50,000/uL 8. Abnormal baseline electrolyte parameters as defined by sodium concentration \<130 mmol/L, potassium concentration \<3 mEq/L or \>6 mEq/L 9. Renal failure as defined by a serum creatinine \>3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels 10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR \> 3.0 or PTT \> 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT. 11. Any active or recent hemorrhage within the past 30 days 12. History of severe allergy (more than rash) to contrast medium 13. Severe, sustained hypertension (Systolic Blood Pressure \>185 mmHg or Diastolic Blood Pressure \>110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled 14. Female who is pregnant or lactating at time of admission 15. Current participation in another investigational drug or device study 16. Presumed septic embolus, or suspicion of bacterial endocarditis 17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization Imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome | 90 days | mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. \- no significant disability despite symptoms; able to carry out all usual duties and activities 2. \- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. \- moderate disability; requiring some help, but able to walk without assistance 4. \- moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. \- severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. \- dead |
| Functional Independence (mRS 0-2), Nested Co-Primary Efficacy Outcome | 90 days | Number of participants with functional independence mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. \- no significant disability despite symptoms; able to carry out all usual duties and activities 2. \- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance |
| Stroke-related Mortality, Primary Safety Outcome | 90 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Revascularization Rates | 24 hours | Revascularization rates at 24 hours from randomization are based on the assessment of vessel patency utilizing CTA/MRA and processed by the CT-MR core laboratory. Revascularization at 24 hours was defined as the presence of partial or complete recanalization. CTA/MRA images utilized ionizing radiation exposure. |
| Good Functional Outcome | 90 days | Proportion of participants with functional independence mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. \- no significant disability despite symptoms; able to carry out all usual duties and activities 2. \- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance |
| Neurological Deterioration From Baseline NIHSS Score | 5-7 days | Neurological deterioration from baseline NIHSS score through Day 5-7/discharge (whichever is earlier) post randomization. Neurological deterioration is defined as ≥ 4 point increase in the NIHSS score from the baseline score. The calculated difference in NIHSS scores was assessed at baseline and Day 5-7/discharge (two time points). The NIHSS is an assessment which objectively quantifies the impairment caused by a stroke. It is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. |
| Early Response | 5-7 Days | The proportion of subjects with early response at Day 5-7/Discharge (whichever is earlier), defined as a National Institutes of Health Stroke Scale (NIHSS) drop of ≥10 from baseline or NIHSS score 0 or 1. The NIHSS is an assessment which objectively quantifies the impairment caused by a stroke. It is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. |
| All Cause Mortality | 90 days | — |
Countries
Australia, Canada, France, Spain, United States
Participant flow
Recruitment details
See protocol
Pre-assignment details
See protocol
Participants by arm
| Arm | Count |
|---|---|
| Trevo Thrombectomy Procedure Trevo Thrombectomy Procedure and Medical Management
Trevo Thrombectomy Procedure: stent retriever; intended to restore blood flow in the neurovasculature by removing thrombus (clot)
Medical Management: Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc | 107 |
| Medical Management Medical Management
Medical Management: Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc | 99 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 20 | 18 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Trevo Thrombectomy Procedure | Medical Management | Total |
|---|---|---|---|
| Age, Continuous | 69.4 Years STANDARD_DEVIATION 14.1 | 70.7 Years STANDARD_DEVIATION 13.2 | 70.0 Years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 16 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 82 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 15 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 15 Participants | 28 Participants |
| Race (NIH/OMB) White | 70 Participants | 63 Participants | 133 Participants |
| Sex: Female, Male Female | 65 Participants | 48 Participants | 113 Participants |
| Sex: Female, Male Male | 42 Participants | 51 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 107 | 18 / 99 |
| other Total, other adverse events | 102 / 107 | 91 / 99 |
| serious Total, serious adverse events | 41 / 107 | 47 / 99 |
Outcome results
Primary
Functional Independence (mRS 0-2), Nested Co-Primary Efficacy Outcome
Number of participants with functional independence mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. \- no significant disability despite symptoms; able to carry out all usual duties and activities 2. \- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
Time frame: 90 days
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | Functional Independence (mRS 0-2), Nested Co-Primary Efficacy Outcome | 52 Participants |
| Medical Management | Functional Independence (mRS 0-2), Nested Co-Primary Efficacy Outcome | 13 Participants |
Primary
Stroke-related Mortality, Primary Safety Outcome
Time frame: 90 days
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | Stroke-related Mortality, Primary Safety Outcome | 17 Participants |
| Medical Management | Stroke-related Mortality, Primary Safety Outcome | 18 Participants |
Primary
Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome
mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. \- no significant disability despite symptoms; able to carry out all usual duties and activities 2. \- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. \- moderate disability; requiring some help, but able to walk without assistance 4. \- moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. \- severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. \- dead
Time frame: 90 days
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trevo Thrombectomy Procedure | Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome | 5.5 score on a scale | Standard Deviation 3.8 |
| Medical Management | Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome | 3.4 score on a scale | Standard Deviation 3.2 |
Secondary
All Cause Mortality
Time frame: 90 days
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | All Cause Mortality | 20 Participants |
| Medical Management | All Cause Mortality | 18 Participants |
Secondary
Early Response
The proportion of subjects with early response at Day 5-7/Discharge (whichever is earlier), defined as a National Institutes of Health Stroke Scale (NIHSS) drop of ≥10 from baseline or NIHSS score 0 or 1. The NIHSS is an assessment which objectively quantifies the impairment caused by a stroke. It is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
Time frame: 5-7 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | Early Response | 51 Participants |
| Medical Management | Early Response | 19 Participants |
Secondary
Good Functional Outcome
Proportion of participants with functional independence mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. \- no significant disability despite symptoms; able to carry out all usual duties and activities 2. \- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
Time frame: 90 days
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | Good Functional Outcome | 52 Participants |
| Medical Management | Good Functional Outcome | 13 Participants |
Secondary
Neurological Deterioration From Baseline NIHSS Score
Neurological deterioration from baseline NIHSS score through Day 5-7/discharge (whichever is earlier) post randomization. Neurological deterioration is defined as ≥ 4 point increase in the NIHSS score from the baseline score. The calculated difference in NIHSS scores was assessed at baseline and Day 5-7/discharge (two time points). The NIHSS is an assessment which objectively quantifies the impairment caused by a stroke. It is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
Time frame: 5-7 days
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | Neurological Deterioration From Baseline NIHSS Score | 15 Participants |
| Medical Management | Neurological Deterioration From Baseline NIHSS Score | 26 Participants |
Secondary
Revascularization Rates
Revascularization rates at 24 hours from randomization are based on the assessment of vessel patency utilizing CTA/MRA and processed by the CT-MR core laboratory. Revascularization at 24 hours was defined as the presence of partial or complete recanalization. CTA/MRA images utilized ionizing radiation exposure.
Time frame: 24 hours
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trevo Thrombectomy Procedure | Revascularization Rates | 82 Participants |
| Medical Management | Revascularization Rates | 38 Participants |