- 1 Clinical Question
- 2 Bottom Line
- 3 Major Points
- 4 Guidelines
- 5 Design
- 6 Population
- 7 Interventions
- 8 Outcomes
- 9 Criticisms
- 10 Funding
- 11 Further Reading
In patients with acute ischemic stroke due to large vessel occlusion, does combined IV t-PA and Solitaire FR within 6 hours of symptom onset lead to less stroke-related disability (mRS) than those subjects treated with IV t-PA alone?
- In patients with acute ischemic stroke with confirmed large-vessel occlusions of the anterior circulation who were treated with intravenous t-PA, additional treatment with the stent retriever within 6 hours after symptom onset improved functional outcomes at 90 days.
- For every 2.6 patients who were treated, 1 additional patient had an improved disability outcome; for every 4.0 patients who were treated, 1 additional patient was functionally independent at 90-day follow-up.
As of May 2015, no guidelines have been published that reflect the results of this trial.
- Multicenter, global, two-arm, prospective, randomized, open, blinded endpoint (PROBE) IDE study
- N=196 (stopped early)
- tPA only (n=98)
- Stent retriever+tPA (n=98)
- Expected randomized sample size 522
- 60 total centers (40 centers in US)
- Enrollment: approximately 49 months
- Follow-up period: 90 days ± 15 days
- Total Study Duration: 52 months
- Primary End Point - 90-day global disability assessed via the blinded evaluation of modified Rankin score (mRS).
- Age 18 – 85
- Clinical signs consistent with acute ischemic stroke
- No prestroke functional dependence (prestroke Modified Rankin Score ≤ 1)
- NIHSS ≥ 8 and < 30 at the time of randomization
- Initiation of IV t-PA within 4.5 hours of onset of stroke symptoms (onset time is defined as the last time when the patient was witnessed to be at baseline), with investigator verification that the subject has received / is receiving the correct IV t-PA dose for the estimated weight prior to randomization.
- Thrombolysis in Cerebral Infarction (TICI) 0-1 flow in the intracranial internal carotid artery, M1 segment of the MCA, or carotid terminus confirmed by CT or MR angiography that is accessible to the Solitaire™ FR Device.
- Subject is able to be treated (with minimum 1 deployment of Solitaire™ FR Device) within 1.5 hours of CTA/PCT or PWI/MRA MRI.
- Subject is willing to conduct protocol-required follow-up visits.
- Subject or subject’s legally authorized representative has signed and dated an Informed Consent Form according to country regulations, ethics committee, and/or IRB requirements.
- History of stroke in the past 3 months.
- Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
- Rapid neurological improvement prior to study randomization suggesting resolution of signs/symptoms of stroke.
- Known serious sensitivity to radiographic contrast agents.
- Current participation in another investigational drug or device treatment study.
- Uncontrolled hypertension defined as systolic blood pressure > 185 or diastolic BP>110 that cannot be controlled except with continuous parenteral antihypertensive medication.
- Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency. (Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment.)
- Warfarin therapy with INR greater than 1.7.
- LMWH as DVT prophylaxis or in full dose within the last 24 hours from screening.
- Subject who has received heparin or a direct thrombin inhibitor within the last 48 hours must have a normal PTT to be eligible.
- Subject who has received factor Xa inhibitor therapy within the past 24 hours must have a normal ecarin clotting time to be eligible. Subject who has received factor Xa inhibitor therapy > 24 hrs ago but < 48 hrs ago must have a normal PTT to be eligible.
- Baseline lab values: glucose <50mg/dl or >400mg/dl, platelets<100,000, or Hct<25
- Renal Failure as defined by a serum Cr>2.0 or GFR<30.
- Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason.
- Life expectancy of less than 90 days.
- Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, cerebral aneurysm, or AV malformation
- Clinical presentation suggests a SAH, even if initial CT or MRI scan is normal.
- Presumed septic embolus, or suspicion of bacterial endocarditis.
- Presumed pericarditis including pericarditis after acute myocardial infarction.
- Suspicion of aortic dissection.
- Surgery or biopsy of parenchymal organ within 30 days.
- Trauma with internal injuries or ulcerative wounds within 30 days.
- Severe head trauma or head trauma with loss of consciousness within 90 days.
- Any active or recent hemorrhage within 30 days.
- Cerebral vasculitis
- Subject with a pre-existing neurological or psychiatric disease that would confound the neurological and functional evaluations.
Imaging Exclusion Criteria:
- CT or MRI evidence of hemorrhage on presentation
- CT showing hypodensity or MRI showing hyperintensity involving greater than 1/3 of the MCA territory (or in other territories, >100 cc of tissue) on presentation
- CT or MRI evidence of mass effect or intra-cranial tumor (except small meningioma)
- Core Infarct and hypoperfusion:
- a. MRI-assessed core infarct lesion greater than:
- • 50 cc for subjects age 18-79 years;
- • 20 cc for subjects age 80-85 years;
- b. CT-assessed core infarct lesion greater than:
- • 40 cc for subjects age 18-79 years;
- • 15 cc for subjects age 80-85 years;
- c. All subjects, severe hypoperfusion lesion (10 sec or more Tmax lesion larger than 100 cc);
- d. All subjects, ischemic penumbra ≥ 15 cc and mismatch ratio >1.8.
- Angiographic evidence of carotid dissection or complete cervical carotid occlusion
- Arterial tortuosity, calcification, pre-existing stent, and/or stenosis which would prevent the device from reaching the target vessel and/or preclude safe recovery of the device
- Enrollment duration - Dec 2012 through Nov 2014
- 196 patients underwent randomization (98 in each group)
- 39 centers in the US and Europe
- Prescreening log data were received on 1470 patients from 33 sites.
- Postconsent screening phase data were collected on 77 patients at 15 sites.
- Among the 77 postconsent screened but not enrolled patients, 6 serious adverse events and 36 nonserious adverse events occurred in the first 72 hours
- Prestroke mRS of zero in 83.0% pts in tPA alone group vs. 82.7% pts in tPA+Solitaire group
- Malignant profile (defined as MRI or CT-assessed core infarct >50cc and/or Tmax>10s lesion more than 100cc) 12.0% in tPA alone group vs. 15.7% in tPA+Solitaire group
- 196 pts randomized (98 in each grp - IV tPA alone vs. IV tPA+Solitaire)
- 87 pts received Solitaire (11 did not)
Comparisons are IV tPA vs. IV tPA+Solitaire.
- Score on mRS at 90 days
- Median score 3 (for IV tPA alone) vs. 2 (for IV tPA+Solitaire) (p<0.001)
- Clinical efficacy outcome
- Functional independence at 90 days
- 35% for IV tPA alone vs. 60% for IV tPA+Solitaire (Risk Ratio 1.70) (95% CI 1.23-2.33) (p<0.001)
- Change in NIHSS score at 27 hours
- IV tPA group (- 3.9 +/- 6.2) vs. IV tPA+Solitaire (-8.5 +/- 7.1) (p<0.001)
- Death at 90 days
- IV tPA (12%) vs. IV tPA+Solitaire (9%) (Risk Ratio 0.74 (0.33-1.68) (p=0.50)
- Successful reperfusion at 27 hrs
- IV tPA group (40%) vs. IV tPA+Solitaire group (83%) [Risk Ratio 2.05 (1.45-2.91)] (p<0.001)
- Within the constraints of the study sample size, no evidence of heterogeneity of treatment effect was detected in any of the 8 prespecified subgroups
- Occlusion location
- Geographic location
- Site of initial administration of tPA
- Time from onset to randomization
- No significant difference in adverse events between the study groups overall or within major organ categories
- No device-specific serious adverse events were observed
- The most common nonserious device-specific adverse event was transient, intraprocedural vasospasm without clinical sequelae
- No significant difference in rates of symptomatic hemorrhage between the two treatment groups
- SAH and ICH (assessed radiologically) were also uncommon
- A homogeneous cohort of patients were treated with intravenous t-PA + Solitaire
- Additional trials needed to delineate the effects of stent-retriever therapy in other populations of patients with acute ischemic stroke (including those ineligible for IV t-PA, those who present > 6 hrs after symptom onset (including wake-up stroke pts), and those with M2 occlusions of MCA or posterior circulation
- Study included a continuous quality-improvement program to improve endovascular workflow efficiency at the participating sites. This would need to be implemented in routine care settings
- All the enrolling sites were tertiary care centers with established stroke-intervention programs staffed by experienced neurointerventionalists. Thus, these results may not be generalizable to clinical sites without requisite neurointerventional expertise