POSITIVE Stroke Clinical Trial

Ischemic Stroke Clinical Trial

Official title:

POSITIVE: PerfusiOn Imaging Selection of Ischemic STroke PatIents for EndoVascular ThErapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01852201
• Other study ID #: PRO23329
• Status: Terminated
• Phase: N/A
• Start date: September 2013
• Est. completion date: May 31, 2017

Study information

• Verified date: November 2019
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. completion date: May 31, 2017
• Est. primary completion date: May 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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.

Locations

Country	Name	City	State
United States	University of Buffalo Neurosurgery	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Tennessee Interventional Associates	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio Health	Columbus	Ohio
United States	Swedish/Colorado Neurological Institute	Englewood	Colorado
United States	Baptist Health	Jacksonville	Florida
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	Fort Sanders Regional Medical Center	Knoxville	Tennessee
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Wisconsin University	Madison	Wisconsin
United States	Methodist Healthcare - Memphis	Memphis	Tennessee
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt University	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Stony Brook Medical Center	Stony Brook	New York
United States	Captial Health	Trenton	New Jersey
United States	Univesity of Massachusetts-Worcester	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants in the 6-12 hr Cohort With Global Disability as Assessed by the Modified Rankin Score (mRS)	The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. A score of 3-6 represents global disability are defined as follows: (3) moderate disability (requiring some help, but able to walk without assistance); (4) moderate severe disability (unable to walk without assistance and unable to attend to own bodily needs without assistance); (5) severe disability (bedridden, incontinent and requiring constant nursing care and attention; and (6) dead.	90 day
Secondary	Percentage of Participants in the 6-12hr Cohort With Good Functional Recovery as Assessed by the Modified Rankin Scale (mRS)	The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. A score of 0-2 represents good functional recovery. The scores are defined as follows: (0) No symptoms at all; (1) No significant disability despite symptoms, able to carry out all usual duties and activities; (2) Slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance.	90 days
Secondary	Percentage of Participants Mortality at 30 Days	Mortality at 30 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.	30 days
Secondary	Percentage of Participants Mortality at 90 Days	Mortality 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.	90 days
Secondary	Percentage of Participants With ICH (Intracranial Hemorrhage) With Neurological Deterioration (NIHSS Worsening >4).	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.	90 days
Secondary	Percentage of Participants With SAE's Related to a Thrombectomy Procedure	A Thrombectomy is an interventional procedure to remove a blood clot (thrombus) from a blood vessel in the brain.; 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.	90 days
Secondary	Arterial Revascularization Measured by TICI 2b or 3 Following Device Use	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.	90 days
Secondary	Percentage of Patients With Serious Adverse Events (SAEs) Related to Thrombectomy Device.	A Thrombectomy device is a device intended to restore blood flow in a vessel in the brain by removing a blood clot (thrombus).	90 days