Acute Ischemic Stroke
Conditions
Brief summary
The objectives of the study are to examine the performance and safety characteristics of the Millipede System when used for revascularization of patients with acute ischemic stroke due to Large Vessel Occlusions (LVOs) and to record associated clinical outcomes.
Detailed description
Ischemic stroke is a life-threatening condition. Annually, approximately 795,000 people in the United States have a stroke. The MARRS study is an interventional, open label, single arm, multi center, prospective clinical investigation. The objectives of the study are to evaluate the performance and safety characteristics of the Millipede System in patients presenting with acute ischemic stroke due to LVOs and to record clinical outcomes.
Interventions
DEVICEMillipede System
Mechanical thrombectomy
Sponsors
Perfuze
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects aged ≥ 18 and ≤ 85 years. 2. Pre-stroke mRS score of ≤ 1. 3. Baseline NIHSS score of ≥ 6. 4. A new focal disabling neurologic deficit consistent with acute cerebral ischemia. 5. Evidence of a large vessel occlusion of the intracranial ICA (including T or L occlusions), the M1 or M2 segments of the MCA, the intracranial vertebral artery, or the basilar artery on magnetic resonance angiography (MRA) or computed tomography angiography (CTA). 6. Subject belongs to one of the following subgroups: 1. Subject is ineligible for thrombolytic therapy, OR 2. Subject is eligible for thrombolytic therapy and thrombolytic therapy was administered without delay and per current practice guidelines. 7. For strokes in the anterior circulation, the following imaging criteria should be met: 1. Magnetic Resonance Imaging (MRI) criterion: volume of diffusion restriction visually assessed as ≤ 50 mL, or Alberta Stroke Program Early CT Score (ASPECTS) 6-10; OR 2. Computed Tomography (CT) criterion: Alberta Stroke Program Early CT Score (ASPECTS) 6-10 on baseline CT or Computed Tomography Angiography (CTA)- source images, or volume of significantly lowered relative Cerebral Blood Flow (rCBF) \<30% (volume of ≤ 50 mL if CT perfusion is performed). 8. For strokes in the posterior circulation, the following imaging criterion should be met: pcASPECTS score 8 to 10 on baseline CT, CTA-source images, or Diffusion- Weighted Imaging (DWI) MRI. 9. The interventionalist estimates that arterial puncture can be completed within 8 hours of onset/last known well. 10. Informed consent obtained in accordance with the applicable country-specific regulations and as approved by the IRB/ REC. 11. Angiographic confirmation of a single large vessel occlusion (mTICI of 0-1) of the intracranial ICA (including T or L occlusions), the M1 or M2 segments of the MCA, the intracranial vertebral artery, or the basilar artery that is accessible to the Millipede System.
Exclusion criteria
1. Known previous stroke within the past 3 months. 2. Females who are known to be pregnant or breastfeeding. 3. In the Investigator's opinion, any known comorbidity (including COVID-19) that may complicate treatment or prevent improvement or follow-up. 4. Subject currently participating in or has previously participated in another trial involving an investigational device or drug within 30 days of enrollment. 5. Known history of severe contrast allergy. 6. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluation. 7. Life expectancy of less than 6 months prior to stroke onset. 8. Known cocaine use at time of treatment. 9. Known history of coagulation factor deficiency or oral anti-coagulant therapy with an International Normalized Ratio (INR) of more than 3.0. 10. Known history of treatment with heparin within 48 hours with a Partial Thromboplastin Time (PTT) more than two times the laboratory normal. 11. Known history of treatment with a direct thrombin inhibitor within 48 hours with a PTT more than 1.5 times the laboratory normal. 12. Known glucose level\< 50 mg/dl (2.78 mmol/L) or \> 400 mg/dl (22.20 mmol/L). 13. Known platelet count \<50,000/µL. 14. Clinical history, past imaging or clinical judgement suggest that the intracranial occlusion is chronic. 15. For all patients, severe sustained hypertension with SBP \>220 mmHg and/or DBP \>120 mmHg; for patients treated with thrombolytic therapy, sustained hypertension despite treatment with SBP \>185 mmHg and/or DBP \> 110 mmHg. 16. Renal failure with serum creatinine ≥3 mg/dL or Glomerular Filtration Rate (GFR) \<30 mL/min. 17. Ongoing seizure due to stroke. 18. Initially treated with intra-arterial thrombolytics or a different neurothrombectomy device before use of the Millipede System. 19. Clinical symptoms of bilateral stroke or stroke in multiple territories. 20. Known history of cerebral vasculitis. 21. Evidence of active systemic infection (e.g. septicemia). Exceptions: common cold, hepatitis B virus (HBV), hepatitis C virus (HCV). 22. Any known hemorrhagic or coagulation deficiency. 23. Evidence of current intracranial hemorrhage on imaging. 24. Significant mass effect with midline shift. 25. Known arterial condition in a proximal vessel that requires treatment or prevents access to the site of occlusion or safe recovery of the investigational device (for example, severe stenosis, complete occlusion in the cervical ICA, tandem occlusion). 26. Suspicion or evidence of aortic dissection, septic embolus, or bacterial endocarditis. 27. Evidence of dissection in the extracranial or intracranial cerebral arteries. 28. Excessive arterial tortuosity that may preclude device placement as determined by CTA/Magnetic Resonance Angiography (MRA) and/or conventional angiography. 29. Evidence of multiple vascular occlusions (e.g., bilateral anterior circulation, anterior/posterior circulation, concurrent occlusions in the anterior cerebral artery (ACA) and MCA, other concurrent ipsilateral occlusions in the same or different territories). 30. CT or MRI showing mass effect or intracranial tumor (apart from small meningioma, ≤ 2 cm in diameter). 31. Known cancer with metastases. 32. Known aneurysm at or near the target treatment segment. 33. Angiographic evidence of known or suspected underlying intracranial vasculopathy or atherosclerotic lesions responsible for the target occlusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ITT Cohort: Rate of Core Lab-adjudicated Reperfusion Success Within Three Passes | Intraprocedural | Proportion of subjects with successful reperfusion, defined as achieving a modified Thrombolysis in Cerebrovascular Infarction (mTICI) score of 2b or greater within ≤3 passes with the Millipede System without additional therapy. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b under these criteria as adjudicated by an independent Core Lab. |
| ITT Cohort: Primary Safety Outcome | From Day 0 (procedure) through to the 90 Day visit. | All AEs will be analyzed, with specific attention to the rate of all intracranial hemorrhage (ICH), including symptomatic intracranial hemorrhage (sICH), subarachnoid hemorrhage (SAH), non-hemorrhagic AEs capable of producing neurological deterioration, and death. |
| ITT Cohort: Supplementary Analysis of Primary Effectiveness Endpoint | Intraprocedural | Proportion of subjects with successful reperfusion, defined as achieving a modified Thrombolysis in Cerebrovascular Infarction (mTICI) score of 2b or greater within 3 passes of Millipede System without additional therapy, and where use of any additional therapy after achieving mTICI ≥b with the Millipede System is defined as failure. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b under these criteria as adjudicated by an independent core lab. |
| PP Cohort: Rate of Core Lab-adjudicated Reperfusion Success Within Three Passes | Intraprocedural | Proportion of subjects with successful reperfusion, defined as achieving a modified Thrombolysis in Cerebrovascular Infarction (mTICI) score of 2b or greater within ≤3 passes with the Millipede System without additional therapy. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b under these criteria as adjudicated by an independent Core Lab. |
| PP Cohort: Primary Safety Outcome | From Day 0 (procedure) through to the 90 Day visit. | All AEs will be analyzed, with specific attention to the rate of all intracranial hemorrhage (ICH), including symptomatic intracranial hemorrhage (sICH), subarachnoid hemorrhage (SAH), non-hemorrhagic AEs capable of producing neurological deterioration, and death. |
| PP Cohort: Supplementary Analysis of Primary Effectiveness Endpoint | Intraprocedural | Proportion of subjects with successful reperfusion, defined as achieving a modified Thrombolysis in Cerebrovascular Infarction (mTICI) score of 2b or greater within 3 passes of Millipede System without additional therapy, and where use of any additional therapy after achieving mTICI ≥b with the Millipede System is defined as failure. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b under these criteria as adjudicated by an independent core lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ITT Cohort: Rate of Functional Independence | 90 days post-procedure | The proportion of patients achieving modified Rankin Scale (mRS) score ≤2, evaluated by certified assessors. The mRS scale ranges from 0 (no symptoms) to 5 (severe disability), with an additional category of 6 for death. |
| ITT Cohort: Rate of All-Cause Mortality | 90 days post-procedure | Proportion of subjects that died within 90 days of the procedure |
| ITT Cohort: Rate of Symptomatic Intracranial Hemorrhage (sICH) | 24-hours post-procedure | Rate of symptomatic intracranial hemorrhage (sICH), as independently adjudicated by the Core Lab and Clinical Events Committee |
| ITT Cohort: Rate of All Intracranial Hemorrhage (ICH) | 24 hours post-procedure | Proportion of subjects with any ICH at 24 hours, as adjudicated by the Core Lab |
| ITT Cohort: Rate of Serious Adverse Device Effects (SADEs) | 90 days post-procedure | Proportion of subjects experiencing one or more SADEs within 90 days post-procedure, as adjudicated by an independent Clinical Events Committee |
| ITT Cohort: Rate of Procedure-Related Serious Adverse Events (PRSAEs) | 90 days post-procedure | Proportion of subjects experiencing one or more procedure-related serious adverse events within 90 days post-procedure, as adjudicated by an independent Clinical Events Committee |
| ITT Cohort: Rate of Embolization to New Territory (ENT) | Intraprocedural | Proportion of subjects with distal emboli on final angiography, as adjudicated by an independent Core Lab |
| ITT Cohort: Proportion of Subjects With Successful Reperfusion at End of the Thrombectomy Procedure | Intraprocedural | Proportion of subjects with mTICI ≥2b at the end of the procedure. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b at the end of the procedure, as adjudicated by an independent Core Lab. |
| ITT Cohort: Proportion of Subjects With Complete or Near Complete Reperfusion at End of the Thrombectomy Procedure | Intraprocedural | Proportion of subjects with mTICI ≥2c at the end of the procedure. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2c at the end of the procedure, as adjudicated by an independent Core Lab. |
| ITT Cohort: Proportion of Subjects With Successful Reperfusion After the First Pass With the Millipede System | Intraprocedural | Proportion of subjects with mTICI ≥2b after the first pass with the Millipede System. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b after the first pass with the Millipede System, as adjudicated by an independent Core Lab. |
| ITT Cohort: Proportion of Subjects With Complete or Near Complete Reperfusion at the End of the First Pass With the Millipede System | Intraprocedural | Proportion of subjects with mTICI ≥2c after the first pass with the Millipede System. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2c after the first pass with the Millipede System, as adjudicated by an independent Core Lab. |
| PP Cohort: Rate of Functional Independence | 90 days post-procedure | The proportion of patients achieving modified Rankin Scale (mRS) score ≤2, evaluated by certified assessors. The mRS scale ranges from 0 (no symptoms) to 5 (severe disability), with an additional category of 6 for death. |
| PP Cohort: Rate of All-Cause Mortality | 90 days post-procedure | Proportion of subjects that died within 90 days of the procedure |
| PP Cohort: Rate of Symptomatic Intracranial Hemorrhage (sICH) | 24-hours post-procedure | Rate of symptomatic intracranial hemorrhage (sICH), as independently adjudicated by the Core Lab and Clinical Events Committee |
| PP Cohort: Rate of All Intracranial Hemorrhage (ICH) | 24 hours post-procedure | Proportion of subjects with any ICH at 24 hours, as adjudicated by the Core Lab |
| PP Cohort: Rate of Embolization to New Territory (ENT) | Intraprocedural | Proportion of subjects with distal emboli on final angiography, as adjudicated by an independent Core Lab |
| PP Cohort: Proportion of Subjects With Successful Reperfusion at End of the Thrombectomy Procedure | Intraprocedural | Proportion of subjects with mTICI ≥2b at the end of the procedure. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b at the end of the procedure, as adjudicated by an independent Core Lab. |
| PP Cohort: Proportion of Subjects With Complete or Near Complete Reperfusion at End of the Thrombectomy Procedure | Intraprocedural | Proportion of subjects with mTICI ≥2c at the end of the procedure. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2c at the end of the procedure, as adjudicated by an independent Core Lab. |
| PP Cohort: Proportion of Subjects With Successful Reperfusion After the First Pass With the Millipede System | Intraprocedural | Proportion of subjects with mTICI ≥2b after the first pass with the Millipede System. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2b after the first pass with the Millipede System, as adjudicated by an independent Core Lab. |
| PP Cohort: Proportion of Subjects With Complete or Near Complete Reperfusion at the End of the First Pass With the Millipede System | Intraprocedural | Proportion of subjects with mTICI ≥2c after the first pass with the Millipede System. The mTICI scale ranges from 0 to 3, with higher scores indicating better reperfusion: 0 = no perfusion, 1 = minimal perfusion, 2a = partial (\<50%), 2b = substantial (≥50%), 2c = near complete, 3 = complete. This measure reports the number of participants who achieved mTICI ≥2c after the first pass with the Millipede System, as adjudicated by an independent Core Lab. |
Countries
France, Spain, United States
Contacts
PRINCIPAL_INVESTIGATORRaul Nogueira, MD
University of Pittsburgh Medical Center (UPMC), Pittsburgh, USA
PRINCIPAL_INVESTIGATORMarc Ribo, MD
Vall D'Hebron Hospital, Barcelona, Spain
PRINCIPAL_INVESTIGATORRicardo Hanel, MD
Baptist Health Research Institute, Jacksonville, USA
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 80 Participants |
| Region of Enrollment Europe | 77 participants |
| Region of Enrollment United States | 103 participants |
| Sex: Female, Male Female | 88 Participants |
| Sex: Female, Male Male | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 25 / 180 |
| other Total, other adverse events | 81 / 180 |
| serious Total, serious adverse events | 57 / 180 |
Outcome results
None listed