Trial Results Prove Potential Benefit From Treating Select Stroke Patients With Minimally Invasive Therapy

Data Fills Significant Gap in Stroke Studies to Date

MIAMI, Aug. 1, 2013 /PRNewswire-USNewswire/ -- Multiple studies have been conducted over the past five to ten years to assess the effectiveness of an evolving trend in acute ischemic stroke treatment - performing Intra-Arterial (IA) treatment or a minimally invasive surgery utilizing specialty devices to snare or dissolve clots that are blocking blood flow within a vessel of the brain. However, because the clinical outcomes from these treatments have never been compared to the outcomes of patients who were IA-eligible but not treated, the long term benefits of these therapies have remained unclear.

With the introduction of  the FIRST Trial¹, a prospective, multi-center study sponsored by Penumbra, Inc. (Alameda, CA), the neuroscience community has the opportunity to assess the natural history of stroke in a population of patients who, circumstances notwithstanding, would have otherwise been treated with IA therapy.  According to Don Frei MD, a neurointerventionist who specializes in IA treatment and co-chair of the Society of Neurointerventional Surgery (SNIS) 10^th Annual Meeting where the study results were reported this week, the trial provides an invaluable opportunity to gather real-world data that clearly shows the natural evolution of ischemic stroke in patients who are not treated. "As all of our IA research to date has focused on single study evaluation, or has compared treatments utilizing various devices, we have not had a valid control group comprised of ideal IA-eligible, but untreated, patients to provide the proper context for our work.  FIRST fills that gap with meaningful data in our field's continuing assessment of IA stroke treatment and its impact."

The FIRST Trial includes 62 patients to date, all of whom met the criteria for IA therapy including presenting with large vessel blockages in both the middle cerebral artery (MCA) and internal cerebral artery (ICA) within the standard eight-hour time window from the onset of stroke symptoms, but were not treated due to various reasons including lack of access to a comprehensive stroke center. Results showed that only 10 percent of patients experienced a restoration of blood flow in the affected brain vessel and only 20.7 percent of patients were functionally independent at 90 days after their stroke event. The remaining patients either died or were permanently disabled, suffering a signficant loss of quality of life.

"We have learned over the years that blocked blood vessels that result in heart attacks need to be re-opened for patients to experience good outcomes from treatment," said Vallabh Janardhan, MD, Director of the Texas Stroke Institute, a regional brain attack network of hospitals in North Texas, and a Principal Investigator of the FIRST trial.

"Our initial results show that blocked blood vessels that result in 'brain attacks' can have devastating outcomes, with close to 80 percent of patients either dying or becoming severely disabled, if IA treatment options are not available within the required timeframe."

When comparing FIRST results with previous studies designed to assess the effectiveness of IA therapy utilizing devices^1-3, the differences in patient outcome are notable.  Blood flow was restored in over 82-85 percent of patients treated with IA therapy as compared to 10 percent of the untreated patients in the First Trial.  Additionally, the proportion of patients who achieved functional independence ranged from 37 to 44.7 percent in IA studies as compared to only 20.7 percent of FIRST Trial patients.   Treated patients also tended to have a much lower rate of mortality than the untreated patients, with a range of 23.6 to 25.3 compared with 41.9 percent, respectively.

In providing a viable control population, the FIRST Trial, Frei says "may very well serve as a benchmark stroke study against which to compare current and future device trials."  Traditionally, many practitioners in the neurointerventional field have looked to the Intra-arterial Prourokinase for Acute Ischemic Stroke Trial (PROACT II), a study comparing  IA/prourokinase plus heparin versus heparin alone, to fill that role.  Published in the Journal of the American Medical Association in 1999,  PROACTII included a control group (heparin alone patients) that is not reflective of the current patient population that would be treated with IA therapy today, says Frei.

When assessing FIRST and PROACT II side by side, differences in entry criteria are notable.  FIRST patients presented to the hospital with MCA or ICA strokes within eight hours as opposed to PROACT II which included only those patients with MCA strokes who arrived at the hospital within six hours.  Following treatment, when comparing only outcomes of MCA strokes, FIRST patients reflected notably worse results with restoration of blood flow in 8 percent of cases and a mortality rate of 36.6 percent as compared to 18 percent  and 27.1 percent, respectively, in PROACT II.  Additionally, when measuring what percentage of patients improved their follow-up National Institute of Health Stroke Scale (NIHSS) score by 50 percent or more, FIRST patients recorded 21.4 percent at seven-day follow-up while 44 percent of PROACT II patients achieved this measure at 90 days. 

"As FIRST patients are representative of the stroke population that we consider for IA therapy today, and their results are considerably worse than those patients in PROACT II, the case can be more clearly made that eligible patients can indeed benefit from advanced therapy," says Janardhan. "With the addition of FIRST data to the growing research portfolio on IA therapy, the scientific community will benefit from the ability to measure future device trials against a viable control population."

Study Background:

The FIRST Trial, a prospective, multi-center, single arm natural history study specified inclusion criteria as large vessel occlusion in the anterior circulation, presentation to hospital within eight hours of symptom onset, a baseline NIHSS score equal to or over 10, patient ineligibility or refractory to lytic therapy and eligibility for but untreated by intra-arterial therapy.  Of 62 study participants,  the mean age was 68 years (+/- 15.6); the median NIHSS score was 18; the percentage of  patients with TIMI (0–1) on presentation was 100 percent; the percentage of patients with TICI (0–1) on presentation was 98.4 percent; and the percentage of patients refractory to IV rtPA was 52 percent.  Of the total study population, 59.7 percent were female; 66 percent suffered MCA strokes; 31 percent suffered from ICA strokes; and 3 percent suffered strokes in other locations.  Results showed that 20.7 percent of patients met the primary endpoint defined as a good functional outcome (modified Rankin Scale of 0–2) at 90 days, and 14.5 percent of patients met the secondary endpoint defined as a NIHSS score of 0-1 at discharge, or an improvement of ten plus points. The study reflected a 41.9 percent mortality rate and an additional 37.4 percent of patients were permanently disabled with significant loss of quality of life. Adverse events occurred in 33.9 percent of patients, and symptomatic and asymptomatic intracranial hemmorhage occurred in 8.1 and 9.7 percent respectively.  Participating study sites under the Texas Stroke Institute (www.texasstrokeinstitute.com) are the Medical Center of Plano, Texas, Plaza Medical Center of Fort Worth, Texas  and Medical City Dallas Hospital, Texas.  Other participating sites are Queen Mary Hospital, The University of Hong Kong, China and the Prince of Wales Hospital, The Chinese University of Hong Kong, China.

About SNIS:

Founded in 1992, the Society of NeuroInterventional Surgery (SNIS) is represented by physicians who specialize in minimally invasive techniques to treat neurovascular conditions, including stroke, aneurysms, carotid stenosis and spinal abnormalities.  Drawing on diverse backgrounds and expertise including interventional neuroradiology, neurosurgery and neurology, these physicians are continuing to forge new pathways in the development of the distinct specialty of neurointervention.  Over the past two decades, practitioners of this field have paved the way for the scientific research and study that has resulted in new technology and revolutionary treatment approaches that have transformed the neurosciences.  In keeping with the mission of SNIS, the society remains committed to working in partnership to advance the science and medical environment that will result in enhanced quality of care for patients across the globe.  www.snisonline.org. Follow us on Twitter @SNISinfo.

1) A Clinical Trial to Assess the Acute Safety and Functional Outcome and Recovery After STROKE: The FIRST Trial (NCT01092819)

2) Evaluation of the Penumbra™ Stroke System in the Revascularization of Patients With Acute Ischemic Stroke Secondary to Intracranial Large Vessel Occlusive Disease (NCT00334061)

3) Penumbra Imaging Collaborative Study (PICS): A Multicenter Trial to Assess Outcome of Patients Revascularized by the Penumbra™ System (NCT00785161)

SOURCE Society of NeuroInterventional Surgery