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Trial record 1 of 1 for:    NCT01852201
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POSITIVE Stroke Clinical Trial

This study is currently recruiting participants.
See Contacts and Locations
Verified September 2015 by Medical University of South Carolina
Sponsor:
Collaborator:
Vanderbilt University
Information provided by (Responsible Party):
Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01852201
First received: April 23, 2013
Last updated: October 1, 2015
Last verified: September 2015
  Purpose

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

Condition Intervention
Ischemic Stroke Device: Endovascular Mechanical Thrombectomy

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: POSITIVE: PerfusiOn Imaging Selection of Ischemic STroke PatIents for EndoVascular ThErapy

Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • rates of good functional outcomes compared to best medical therapy (MT) - measured by Modified rankin score (mRS) [ Time Frame: 90 days ]
    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.


Secondary Outcome Measures:
  • • 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS [ Time Frame: 90 day ]
    mRS at 90 day will be compared to baseline mRS and data analyzed to analyze any relationship within the 6-12 hr cohort and their treatment arm

  • • Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days [ Time Frame: 90 days ]

    within in the 6-12 cohort, an analysis will be performed comparing study arms for good functional outcomes by mRS at 90 days.

    Secondary outcome endpoints will be compared between randomized groups in an ITT fashion; with overall Type I error controlled using hierarchical testing. That is, if statistical significance is observed on the primary effectiveness endpoint, the secondary clinical efficacy endpoints will then be tested in sequential fashion each at a two-sided alpha level of 0.05, with testing ceasing once a null hypothesis cannot be rejected. The statistical tests will be performed in the order specified above


  • • Mortality at 30 and 90 days [ Time Frame: 30 and 90 days ]
    • Mortality at 30 and 90 days will be compared between randomized groups in an ITT fashion; with overall Type I error controlled using hierarchical testing. That is, if statistical significance is observed on the primary effectiveness endpoint, the secondary clinical efficacy endpoints will then be tested in sequential fashion each at a two-sided alpha level of 0.05, with testing ceasing once a null hypothesis cannot be rejected.

  • • Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days [ Time Frame: 90 days ]
    • Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days will be compared between randomized groups in an ITT fashion; with overall Type I error controlled using hierarchical testing. That is, if statistical significance is observed on the primary effectiveness endpoint, the secondary clinical efficacy endpoints will then be tested in sequential fashion each at a two-sided alpha level of 0.05, with testing ceasing once a null hypothesis cannot be rejected.

  • • ICH with neurological deterioration (NIHSS worsening >4). [ Time Frame: 90 days ]
    • ICH with neurological deterioration (NIHSS worsening >4) will be compared between randomized groups in an ITT fashion; with overall Type I error controlled using hierarchical testing. That is, if statistical significance is observed on the primary effectiveness endpoint, the secondary clinical efficacy endpoints will then be tested in sequential fashion each at a two-sided alpha level of 0.05, with testing ceasing once a null hypothesis cannot be rejected.

  • • Procedure related SAE's [ Time Frame: 90 days ]
    • Procedure related SAE's will be compared between randomized groups in an ITT fashion; with overall Type I error controlled using hierarchical testing. That is, if statistical significance is observed on the primary effectiveness endpoint, the secondary clinical efficacy endpoints will then be tested in sequential fashion each at a two-sided alpha level of 0.05, with testing ceasing once a null hypothesis cannot be rejected.

  • • Arterial revascularization measured by TICI 2b or 3 following device use [ Time Frame: 90 days ]
    • Arterial revascularization measured by TICI 2b or 3 following device use will be compared between randomized groups in an ITT fashion; with overall Type I error controlled using hierarchical testing. That is, if statistical significance is observed on the primary effectiveness endpoint, the secondary clinical efficacy endpoints will then be tested in sequential fashion each at a two-sided alpha level of 0.05, with testing ceasing once a null hypothesis cannot be rejected.


Estimated Enrollment: 750
Study Start Date: September 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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
Experimental: 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.
Device: 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.
Other Name: mechanical revascularization

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

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852201

Contacts
Contact: Adrian Parker 843-792-3164 parkerad@musc.edu

Locations
United States, Florida
Baptist Health Recruiting
Jacksonville, Florida, United States, 32207
Contact: Ricardo Hanel, MD         
Principal Investigator: Ricardo Hanel, MD         
United States, Massachusetts
Univesity of Massachusetts-Worcester Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Ajit Puri, MD         
Principal Investigator: Ajit Puri, MD         
United States, New Jersey
Captial Health Recruiting
Trenton, New Jersey, United States, 08638
Contact: Erol Veznedaroglu, MD         
Principal Investigator: Erol Veznedaroglu, MD         
United States, New York
Albany Medical Center Not yet recruiting
Albany, New York, United States, 12208-3412
Contact: Alan Boulos, MD    518-262-5088      
Principal Investigator: Alan Boulos, MD         
University of Buffalo Neurosurgery Recruiting
Buffalo, New York, United States, 14203
Contact: Adnan Siddiqui, MD         
Principal Investigator: Adnan Siddiqui, MD         
Stony Brook Medical Center Recruiting
Stony Brook, New York, United States, 11764
Contact: David Fiorella         
Principal Investigator: David Fiorella, MS         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Gabor Toth, MD         
Principal Investigator: Gabor Toth, MD         
Ohio Health Recruiting
Columbus, Ohio, United States, 43214
Contact: Ronald Budzik, MD         
Principal Investigator: Ronald Budzik, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29461
Contact: Adrian Parker    843-792-3164    parkerad@musc.edu   
Principal Investigator: Aquilla Turk, DO         
Sub-Investigator: Raymond Turner, MD         
Sub-Investigator: M. Imran Chaudry, MD         
Sub-Investigator: Alejandro Spiotta, MD         
United States, Tennessee
Tennessee Interventional Associates Recruiting
Chattanooga, Tennessee, United States, 37403
Contact: Blaise Baxter, MD         
Principal Investigator: Blaise Baxter, MD         
Methodist Healthcare - Memphis Recruiting
Memphis, Tennessee, United States, 38104
Contact: Adam Arthur, MD         
Principal Investigator: Adam Arthur, MD         
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: J Mocco, MD         
Principal Investigator: J Mocco, MD         
United States, West Virginia
West Virginia University Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Ansaar Rai, MD         
Principal Investigator: Ansaar Rai, MD         
United States, Wisconsin
Wisconsin University Recruiting
Madison, Wisconsin, United States, 98374
Contact: Beverly Aagaard-Kienitz, MD         
Principal Investigator: Beverly Aagaard-Kienitz, MD         
Sponsors and Collaborators
Medical University of South Carolina
Vanderbilt University
Investigators
Principal Investigator: Aquilla Turk, DO Medical University of South Carolina
  More Information

Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01852201     History of Changes
Other Study ID Numbers: PRO23329
Study First Received: April 23, 2013
Last Updated: October 1, 2015

Additional relevant MeSH terms:
Stroke
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on June 23, 2017