Thrombectomy in Patients Ineligible for iv tPA | NCT02135926

NCT02135926

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
DRKS00005792	Registry Identifier	Deutsches Register Klinischer Studien

Status Module

Name	Class
University Hospital, Aachen	OTHER
University Hospital Augsburg	OTHER
Vivantes Krankenhaus Berlin Neukölln	UNKNOWN
Ruhr University of Bochum

Description Module

Detailed Description

This is a prospective, binational (Germany and Austria), two-arm, randomized, controlled, open label, blinded endpoint post-market study to compare the safety and effectiveness of stent retrievers for thrombectomy compared to best medical treatment alone in acute ischemic stroke (AIS) patients not eligible for IV-tPA treatment.

Patients who meet the inclusion criteria will be randomized to one of the following two treatment arms:

best medical care alone or
best medical care plus endovascular thrombectomy with stent retriever (referred to as thrombectomy).

Endpoints in this prospective open label study will be assessed blinded to the treatment assignment of the patient (PROBE design). This study will be conducted in up to 20 centers in Germany and Austria. This is an adaptive design study, in which there are prospectively stated interim analyses with specified stopping rules, which allow for the possibility of the study to terminate early based on either a determination of study success or of the futility to continue further enrollment.

Up to six hundred (600) subjects, 300 per treatment group, will be enrolled and randomized in the study for the Intent to Treat (ITT) analysis set. The randomization will be stratified by time from symptom onset and stroke severity (NIHSS). The expected duration of each subject"s enrollment is approximately 90 days. Subjects will be followed with assessments at 30 (+/-6) hours, hospital discharge, and 90 (+/-14) days post stroke.

A blinded core laboratory will assess baseline imaging to confirm vessel occlusion and determine ASPECT score, 30 (+/- 6) hours post treatment imaging to assess presence of ICH, and to measure core infarct volume.

The primary effectiveness endpoint for a subject is the blinded evaluation of the ordinal mRS outcome at 90 days post-stroke. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in mRS outcomes at 90 days post-stroke between treatment groups ("mRS shift analysis").

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Best medical care	Active Comparator	Best clinical care in dedicated stroke unit	Other: Best medical care
Thrombectomy	Active Comparator	All subjects randomly assigned to the thrombectomy arm, except those with rapidly improving neurologic symptoms or no angiographic evidence of occlusion, will be treated with the endorsed study devices (stent retriever).	Device: Thrombectomy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Thrombectomy	Device	Stent retriever are intended to restore blood flow in patients with acute ischemic stroke secondary to intracranial occlusive vessel disease by providing temporary bypass across the occlusion and/or by the non-surgical removal of emboli and thrombi. They may be used with aspiration and with the injection or infusion of contrast media and/or other fluids. For subjects enrolled in this protocol who are randomly assigned to undergo the thrombectomy procedure, the device will be used according to the Instructions-for-Use (IFU) that is packaged with the device.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
mRS Shift	The primary endpoint of the trial is the modified Rankin Scale (mRS) outcome at 90 days poststroke. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in ordinal mRS outcomes at 90 days postprocedure between treatment groups ("mRS shift analysis"). The null and alternative hypotheses are β ≥ 0 and β < 0, respectively, where β is the treatment arm parameter in a proportional-odds logistic model with mRS category as response variable.	90 (+/-14) days after treatment

Secondary Outcomes

Measure	Description	Time Frame
Neurological outcome	Good neurological outcome with 90-day modified rankin Scale (mRS) ≤2 Good neurological outcome with 90-day NIHSS (National Institutes of Health Stroke Scale) improvement ≥10 from baseline Excellent neurological outcomes with 90-day mRS≤1	90 (+/- 14) days after treatment
Health Status

Other Outcomes

Measure	Description	Time Frame
Safety endpoints	Number of patients with any of the following: Death or dependency (mRS 5-6) Symptomatic intracranial haemorrhage (sICH) at 30 (-/+ 6) hours (CT or MRI) as defined in Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), European Cooperative Acute Stroke Study (ECASS) II, National Institute of Neurological Disorders and Stroke (NINDS); Parenchymal hemorrhage type 2 (PH-2) Neurological deterioration within 7 days defined as an increase in NIHSS score by 4 or more points from baseline Adverse Events (AEs) Serious AEs (SAEs), Adverse Device Effects (ADEs), and Serious Adverse Device Effects (SADEs) including Unanticipated Adverse Device Effects (UADEs attributed to the stent retriever, reported in the interventional treatment arm Mortality rates at discharge and 90 days post-stroke Overall (all-cause mortality) death and stroke-related death Space-occupying infarction (malignant brain edema) New ischemic stroke

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patient is ineligible for treatment with IV tPA according to licensing criteria (e.g.

anticoagulation, previous surgery, or beyond 4.5 hours after symptom onset).

Randomization within 7 hours after stroke onset.
Endovascular treatment is expected to be finished within 8 hours after symptom onset by judgment of the interventional Neuroradiologist in charge.
Patient must demonstrate clinical signs and symptoms attributable to target area of occlusion consistent with the diagnosis of ischemic stroke, including impairment of the following: language, motor function, sensation, cognition, gaze, and/or vision for at least 30 minutes without relevant improvement.
Female and male patient between 18-80 years of age
NIHSS Score of >7 and <25
Patient signed informed consent (IC) form by patient, legal representative, or by an independent physician who is familiar with this types of illness if the other options are not possible.
A new focal occlusion confirmed by imaging (MRA/CTA) to be accessible to the thrombectomy device, and located in the M1 of the middle cerebral artery (MCA) and/or the intracranial segment of the distal internal carotid artery (ICA).
Prior to new focal neurological deficit, mRS score was ≤1.

Exclusion Criteria:

Patient is eligible for and receives IV tPA according to licensing criteria
Patient with an international normalized ratio (INR) of >3
Patient is an active participant in another drug or device treatment trial for any disease state, or patient is expected to start participation in another drug or device treatment trial while enrolled in this protocol, unless approved by Sponsor.
Patient has pre-existing neurological or psychiatric disease that could impede the study results or would confound the neurological or functional evaluations.
Patient has carotid dissection, high grade stenosis ≥ 70% proximal to occlusion that requires stenting, or excessive tortuosity to gain access to occlusion, as determined by MRA/ CTA of neck and head.
Patient has vascular disease preventing endovascular treatment (e.g. aortic dissection or aneurysm, no arterial transfemoral access)
Patient has history of contraindication for contrast medium.
Patient is known to have infective endocarditis
CT scan or MRI with evidence of: Mass effect or intracranial tumor, or hypodensity on unenhanced CT and cerebral blood volume (CBV) drop on CBV maps on Computed Tomography Perfusion (CTP), or, alternatively as per institutional standard, restricted diffusion on Diffusion weighted imaging (DWI) with an Alberta Stroke Program Early CT score (ASPECTs) of 6 or less
Female of childbearing potential who is known to be pregnant and/or lactating or who has a positive pregnancy test on admission.
Patient"s anticipated life expectancy is less than 6 Months.

Name	Affiliation	Role
Martin Bendszus, MD	University Hospital Heidelberg	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg		Linz		4020	Austria

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
18388338	Background	Kelly ME, Furlan AJ, Fiorella D. Recanalization of an acute middle cerebral artery occlusion using a self-expanding, reconstrainable, intracranial microstent as a temporary endovascular bypass. Stroke. 2008 Jun;39(6):1770-3. doi: 10.1161/STROKEAHA.107.506212. Epub 2008 Apr 3.
22932714	Background	Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, Liebeskind DS, Smith WS; TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012 Oct 6;380(9849):1231-40. doi: 10.1016/S0140-6736(12)61299-9. Epub 2012 Aug 26.

ID	Term
D000083242	Ischemic Stroke
D020521	Stroke
D020520	Brain Infarction

ID	Term
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D017131	Thrombectomy
D000072700	Conservative Treatment

ID	Term
D014656	Vascular Surgical Procedures
D013504	Cardiovascular Surgical Procedures
D013514	Surgical Procedures, Operative
D013812	Therapeutics