Clinical trial NCT01852201: POSITIVE Stroke Clinical Trial
Official title: POSITIVE: PerfusiOn Imaging Selection of Ischemic STroke PatIents for EndoVascular ThErapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ischemic Stroke
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Vanderbilt University
First posted: 2013-05-13
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Primary Endpoint:

The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, with appropriate image selection, treated with mechanical thrombectomy within 6-12 hours of symptom onset have less stroke related disability and improved good functional outcomes as compared to those treated with best MT with respect to endpoint defined as:

• 90-day global disability assessed via the modified Rankin score (mRS), analyzed using raw mRS scores. Statistical details can be found in section 7.2.

Secondary Endpoints:

* 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS
* Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days
* Mortality at 30 and 90 days
* Intracranial hemorrhage with neurological deterioration (NIHSS worsening \>4) within 24 hours of randomization
* Procedure related serious adverse events (SAE's)
* Arterial revascularization measured by TICI 2b or 3 following device use

Detailed description: Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has shown potential benefit out to 4.5 hours. Mechanical thrombectomy for AIS patients has been shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression of thrombectomy devices over the last several years has resulted in faster recanalization times while maintaining a high degree of safety. This has resulted in improved patient outcomes, similar to prior randomized trial data showing improved outcomes over medical therapy or earlier devices. Data from the MERCI trial suggests that patients \> 85 as well as those with a baseline NIHSS score \> 30 are unlikely to benefit from thrombectomy. Patients with rapidly improving neurologic deficits likely will have an excellent recovery with conventional care, precluding the ability to detect a beneficial treatment effect of thrombectomy.

Pilot data incorporating physiologic imaging has shown that appropriate patients can be selected for thrombectomy. This selection methodology has shown the ability to maintain the same level of safety and efficacy as those patients treated in the highly selective environment of a clinical trial, despite presenting far beyond accepted time based standards. Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population, particularly since no data currently is available addressing the comparability of imaging penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be reproducible at multiple centers and with different imaging modalities. However, all prospective interventional stroke studies performed to date have been restricted by the 8-hour time window.

Eligibility criteria: Inclusion Criteria:

1. Age 18 and older (i.e., candidates must have had their 18th birthday)
2. NIHSS ≥8 at the time of neuroimaging
3. Presenting or persistent symptoms within 6-12 hours of when groin puncture can be obtained
4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1 bifurcation)
5. The operator feels that the stroke can be appropriately treated with traditional endovascular techniques (endovascular mechanical thrombectomy without adjunctive devices such as stents)
6. Pts are within 6-12 hours of symptom onset, that have received IV-tPA without improvement in symptoms are eligible for this study. Patients presenting earlier than 6 hours should be treated according to local standard of care.
7. Pre-event Modified Rankin Scale score 0-1
8. Consenting requirements met according to local IRB

Exclusion Criteria:

1. Patient is less than 6-hours from symptom onset
2. Rapidly improving neurologic examination
3. Absence of large vessel occlusion on non-invasive imaging
4. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory
5. Absence of an associated large penumbra as defined by physiologic imaging according to standard of practice at the participating institution
6. Any intracranial hemorrhage in the last 90 days
7. Known irreversible bleeding disorder
8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \> 2.5 or institutionally equivalent prothrombin time of 2.5 times normal
9. Platelet count \< 100 x 103 cells/mm3 or known platelet dysfunction
10. Inability to tolerate, clinically documented evidence in medical history of adverse reaction to, or contraindication to medications used in treatment of the stroke
11. Contraindication to CT and MRI (i.e., iodine contrast allergy or other condition that prohibits imaging from either CT or MRI)
12. Known allergy to contrast used in angiography that cannot be medically controlled
13. Relative contraindication to angiography (e.g., serum creatinine \> 2.5 mg/dL)
14. Women who are currently pregnant or breast-feeding (Women of child-bearing potential must have a negative pregnancy test prior to the study procedure (either serum or urine)
15. Evidence of active infection (indicated by fever at or over 99.9 °F and/or open draining wound) at the time of randomization
16. Current use of cocaine or other vasoactive substance
17. Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 90 days
18. Patients who lack the necessary mental capacity to participate or are unwilling or unable to comply with the protocol's follow up appointment schedule (based on the investigator's judgment)

Head CT or MRI Scan Exclusion Criteria

* Presence of blood on imaging (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.)
* High density lesion consistent with hemorrhage of any degree
* Significant mass effect with midline shift
* Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan or ASPECTS of \< 7; Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment

Primary outcomes:
measure: Rate of Good Functional Outcomes Measured by Modified Rankin Score (mRS)
timeFrame: 90 days
Secondary outcomes:
measure: Percentage of Participants in the 6-12 hr Cohort With Global Disability as Assessed by the Modified Rankin Score (mRS)
timeFrame: 90 day
measure: Percentage of Participants in the 6-12hr Cohort With Good Functional Recovery as Assessed by the Modified Rankin Scale (mRS)
timeFrame: 90 days
measure: Percentage of Participants Mortality at 30 Days
timeFrame: 30 days
measure: Percentage of Participants Mortality at 90 Days
timeFrame: 90 days
measure: Percentage of Participants With ICH (Intracranial Hemorrhage) With Neurological Deterioration (NIHSS Worsening >4).
timeFrame: 90 days
measure: Percentage of Participants With SAE's Related to a Thrombectomy Procedure
timeFrame: 90 days
measure: Arterial Revascularization Measured by TICI 2b or 3 Following Device Use
timeFrame: 90 days
measure: Percentage of Patients With Serious Adverse Events (SAEs) Related to Thrombectomy Device.
timeFrame: 90 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Englewood
country: United States
facility: Swedish/Colorado Neurological Institute
state: Colorado
city: Jacksonville
country: United States
facility: Baptist Health
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Worcester
country: United States
facility: Univesity of Massachusetts-Worcester
state: Massachusetts
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Trenton
country: United States
facility: Captial Health
state: New Jersey
city: Buffalo
country: United States
facility: University of Buffalo Neurosurgery
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Interventional Associates
state: Tennessee
city: Knoxville
country: United States
facility: Fort Sanders Regional Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Methodist Healthcare - Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: Wisconsin University
state: Wisconsin
Study officials:
affiliation: Medical University of South Carolina
name: Jonathan Lena, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roaldsen MB, Jusufovic M, Berge E, Lindekleiv H. Endovascular thrombectomy and intra-arterial interventions for acute ischaemic stroke. Cochrane Database Syst Rev. 2021 Jun 14;6(6):CD007574. doi: 10.1002/14651858.CD007574.pub3.
citation: Mocco J, Siddiqui AH, Fiorella D, Alexander MJ, Arthur AS, Baxter BW, Budzik RF, Froehler MT, Hanel RA, Lena J, Persaud S, Puri AS, Rai AT, Wintermark M, Woodward K, Zhang X, Turk A. POSITIVE: Perfusion imaging selection of ischemic stroke patients for endovascular therapy. J Neurointerv Surg. 2022 Feb;14(2):126-132. doi: 10.1136/neurintsurg-2021-017315. Epub 2021 Feb 25.