POSITIVE Stroke Clinical Trial

NCT ID: NCT01852201

Last Updated: 2019-11-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-05-31

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.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Best medical therapy

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Endovascular treatment

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.

Group Type: EXPERIMENTAL

Endovascular Mechanical Thrombectomy

Intervention Type: 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.

Interventions

Endovascular Mechanical Thrombectomy

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.

Intervention Type: DEVICE

Other Intervention Names

mechanical revascularization

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)

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Lena, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Swedish/Colorado Neurological Institute

Englewood, Colorado, United States

Baptist Health

Jacksonville, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Univesity of Massachusetts-Worcester

Worcester, Massachusetts, United States

Saint Luke's Hospital

Kansas City, Missouri, United States

Captial Health

Trenton, New Jersey, United States

University of Buffalo Neurosurgery

Buffalo, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Stony Brook Medical Center

Stony Brook, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio Health

Columbus, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Tennessee Interventional Associates

Chattanooga, Tennessee, United States

Fort Sanders Regional Medical Center

Knoxville, Tennessee, United States

Methodist Healthcare - Memphis

Memphis, Tennessee, United States

Vanderbilt University

Nashville, Tennessee, United States

West Virginia University

Morgantown, West Virginia, United States

Wisconsin University

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34125952 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33632884 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO23329

Identifier Type: -

Identifier Source: org_study_id