POSITIVE Stroke Clinical Trial

Medical University of South Carolina (MUSC)

Status: Terminated

Conditions: Ischemic Stroke

Treatments: Device: Endovascular Mechanical Thrombectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT01852201

PRO23329

Details and patient eligibility

About

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

Full 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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Best medical therapy

No Intervention group

Description:

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 group

Description:

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.

Treatment:

Device: Endovascular Mechanical Thrombectomy