POSITIVE Stroke Clinical Trial

NCT01852201 | Terminated Results DMC

• 1 other identifier: PRO23329
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 20

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

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Rate of Good Functional Outcomes Measured by Modified Rankin Score (mRS)

  Modified rankin score measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The range is 0-6 (0 is highest function with no symptoms and 6 is death). This outcome measured percentage of subjects with a "good" functional outcome with a score ranging from 0-2. The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, (patients seen within 6 hours of symptom onset will be immediately considered for endovascular therapy according to the site's standard of care. Likewise, patients presenting beyond 12 hours will be treated according to the site's standard of care), 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.

  90 days

Secondary Outcomes (8)

• Percentage of Participants in the 6-12 hr Cohort With Global Disability as Assessed by the Modified Rankin Score (mRS)

  90 day

• Percentage of Participants in the 6-12hr Cohort With Good Functional Recovery as Assessed by the Modified Rankin Scale (mRS)

  90 days

• Percentage of Participants Mortality at 30 Days

  30 days

• Percentage of Participants Mortality at 90 Days

  90 days

• Percentage of Participants With ICH (Intracranial Hemorrhage) With Neurological Deterioration (NIHSS Worsening >4).

  90 days

Study Arms (2)

Best medical therapy

NO INTERVENTION

Patients randomized to the control group will receive best conventional MT for acute ischemic stroke as determined by the attending stroke physician. Standardization of medical management in both arms will occur according to the following: * General medical management according to AHA/ASA guidelines * Admission to monitored or intensive care unit for at least 24 hours * Aggressive hypertensive-hypervolemic therapy should be used only in the case of symptomatic blood pressure fluctuations or if blood pressure drops below the normal range for the patient * Antithrombotics: ASA 325 mg PO qd for 7 days (clopidogrel may be used as adjunctive therapy if indicated for cardiac disease) then per discretion of treating physician * Close monitoring of BP and glucose with treatment according to AHA/ASA guidelines * Follow-up imaging study required in any patient with neurologic deterioration

Endovascular treatment

EXPERIMENTAL

Endovascular intervention can be performed under either general anesthesia or conscious sedation based on best practices as determined by treating physician. Attempt should be made to expedite the transition from imaging to treatment in as rapid a fashion as possible. The subject should be prepared for the planned interventional procedure according to standard hospital procedures. Mechanical revascularization should be performed with the operators standard thrombectomy technique using aspiration or a stent retriever, separately or in combination.

Device: Endovascular Mechanical Thrombectomy

Interventions

Endovascular Mechanical Thrombectomy DEVICE

Endovascular intervention can be performed under either general anesthesia or conscious sedation based on best practices as determined by treating physician. Attempt should be made to expedite the transition from imaging to treatment in as rapid a fashion as possible. The subject should be prepared for the planned interventional procedure according to standard hospital procedures. Mechanical revascularization should be performed with the operators standard thrombectomy technique using aspiration or a stent retriever, separately or in combination.

Also known as: mechanical revascularization

Endovascular treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 and older (i.e., candidates must have had their 18th birthday)
• NIHSS ≥8 at the time of neuroimaging
• Presenting or persistent symptoms within 6-12 hours of when groin puncture can be obtained
• Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1 bifurcation)
• The operator feels that the stroke can be appropriately treated with traditional endovascular techniques (endovascular mechanical thrombectomy without adjunctive devices such as stents)
• 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.
• Pre-event Modified Rankin Scale score 0-1
• Consenting requirements met according to local IRB

You may not qualify if:

• Patient is less than 6-hours from symptom onset
• Rapidly improving neurologic examination
• Absence of large vessel occlusion on non-invasive imaging
• Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory
• Absence of an associated large penumbra as defined by physiologic imaging according to standard of practice at the participating institution
• Any intracranial hemorrhage in the last 90 days
• Known irreversible bleeding disorder
• 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
• Platelet count \< 100 x 103 cells/mm3 or known platelet dysfunction
• Inability to tolerate, clinically documented evidence in medical history of adverse reaction to, or contraindication to medications used in treatment of the stroke
• Contraindication to CT and MRI (i.e., iodine contrast allergy or other condition that prohibits imaging from either CT or MRI)
• Known allergy to contrast used in angiography that cannot be medically controlled
• Relative contraindication to angiography (e.g., serum creatinine \> 2.5 mg/dL)
• 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)
• Evidence of active infection (indicated by fever at or over 99.9 °F and/or open draining wound) at the time of randomization

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Vanderbilt University: collaborator

Study Sites (20)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Swedish/Colorado Neurological Institute

Englewood, Colorado, 80113, United States

Location

Baptist Health

Jacksonville, Florida, 32207, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Univesity of Massachusetts-Worcester

Worcester, Massachusetts, 01655, United States

Location

Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

Captial Health

Trenton, New Jersey, 08638, United States

Location

University of Buffalo Neurosurgery

Buffalo, New York, 14203, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Stony Brook Medical Center

Stony Brook, New York, 11764, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio Health

Columbus, Ohio, 43214, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29461, United States

Location

Tennessee Interventional Associates

Chattanooga, Tennessee, 37403, United States

Location

Fort Sanders Regional Medical Center

Knoxville, Tennessee, 37916, United States

Location

Methodist Healthcare - Memphis

Memphis, Tennessee, 38104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Wisconsin University

Madison, Wisconsin, 98374, United States

Location

Related Publications (2)

• 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.

  PMID: 34125952 DERIVED

• 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.

  PMID: 33632884 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Jonathan Lena, MD
• Organization: Medical University of SC

lena@musc.edu

843-792-9226

Study Officials

• Jonathan Lena, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: May 13, 2013
• Study Start: September 1, 2013
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: November 13, 2019
• Results First Posted: November 13, 2019

Record last verified: 2019-11

Locations

US (20)