Interim results from the START trial, presented at Society of NeuroInterventional Surgery (SNIS, San Diego, USA) 9th Annual Meeting, show advancement in predicting which patients suffering from ischaemic stroke will benefit from endovascular therapy.
The START (Stroke Treatment and Revascularization Therapy) trial results, sponsored by Penumbra, is one of the first prospective, core-lab adjudicated, multicentre studies to show a correlation between an image of the patient’s brain before treatment and their recovery after clot aspiration. Specifically, the study evaluated information from a brain scan about the amount of tissue affected by a stroke prior to treatment, and showed that it can be used to predict outcomes in patients undergoing endovascular care with the Penumbra System, an aspiration thrombectomy device used to remove clots from large vessels of the brain. These preliminary results show that higher pre-treatment ASPECTS on CTA source images are associated with better outcomes following endovascular therapy. Comparative studies versus NCCT ASPECTS are necessary to determine their relative accuracy for outcome prediction, noted the investigators.
Currently, there is no standard imaging technique to suggest which patients suffering from acute ischaemic stroke should receive endovascular therapy. The CAT Scan (CT) remains the most widely used modality for stroke evaluation, but is primarily used to rule out bleeding. Changes on a non-contrast CT as measured by the ASPECTS score, a way of evaluating early effects of a stroke, have been shown to predict response to endovascular therapy. To date, however, definitive studies proving the value of CT-Angiography Source Images (CTA-SI) in assessing stroke treatment outcomes are lacking. The START trial provides initial answers to fill that void, especially considering the often complicated process involved in evaluating stroke patients beyond the traditional 3 to 4.5 hour window when clot-busting drugs cannot be used and treatment utilising devices may be optimal.
“Aside from the value of this study to the individual practitioner, these results have significant implications for the collective neurointerventional community,” said Donald F Frei, director of Neurointerventional Surgery, Radiology Imaging Associates/Swedish Medical Center in Denver, Colorado, and a principal investigator of the START trial.
A total of 77 patients at 15 centres met study criteria, which required patients to show evidence of large vessel occlusion within eight hours of symptom onset and a NIH Stroke Scale (NIHSS) score >10. Those who presented within three hours must have been ineligible or not responsive to intravenous drug therapy. The imaging method included in the study was at each centre’s discretion and included non-contrast CT, CTA-SI, CT perfusion, or MRI diffusion imaging. This analysis focused on the preliminary CTA-SI results. Overall results showed a positive neurological outcome rate (modified Rankin Score ≤2 at 90 days) of 48.1% (37/77). This is the highest rate of positive neurological outcomes in any prospective, multicentre, core-lab adjudicated study of interventional stroke treatment with any device to date.
Moreover, when the pre-specified ASPECTS classifications, 0–4 (large infarct), 5–7 (medium infarct), and 8–10 (small infarct) are used, the outcomes become differentiated. The rate of good outcomes is only 20% for patients with ASPECTS 0–4, but 55.8% for 5–7, and 64.3% for 8–10 (p=0.08). Adjusting for age and stroke severity and comparing ASPECTS 0–4 with the ASPECTS 5–10 group, pre-ASPECTS 5–10 was an independent predictor of good outcome (Odds Ratio 6.8, p=0.006).
NeuroNews talked to Frei about the study
The START trial interim results have shown that pre-ASPECTS 5–10 score was an independent predictor of good outcome with endovascular therapy. Based on these results, what is your key message to members of the neurointerventional community?
“While endovascular therapy is an accepted approach to treating stroke, only a small percentage are actually treated interventionally since it is not available in all stroke centres as a standard of care and there is not standard protocol for patient selection as yet.
“The pre-ASPECTS reading from this study suggests the ability for surgeons to conduct a fast, easy-to-obtain CTA source image that can guide patient selection for endovascular therapy, particularly those most likely to benefit from the Penumbra System, beyond the 3–4.5 hour window associated with current intravenous therapy.
“Generally stroke requires a quick but accurate assessment of the best treatment options for the patient. Aside from the value of this study to the individual practitioner, these results have significant implications for the collective neurointerventional community because this information can more rigorously define techniques to help ensure stroke patients receive the best possible treatment as fast as possible.”
What were some of the limitations of the study…how much caution should be utilised when applying its results to clinical practice?
“These are results from a preliminary analysis of the START trial, so the results are not yet final, but they point in a very promising direction for endovascular therapy. Overall results from the START trial showed a positive clinical outcome rate of 48.1% with the Penumbra System, which is the only endovascular therapy on the market today that uses aspiration at the point of the clot to restore blood flow. This is the highest rate of positive neurological outcomes in any prospective, multicentre, core-lab adjudicated study of interventional stroke treatment with any device to date, and a very promising indicator for the future of endovascular stroke treatment.”
Joshua Hirsch, director of the Neuroendovascular Program, chief of Minimally Invasive Spine Surgery and associate vice chair of Interventional Care, Massachussetts General, Boston, USA and the president of SNIS told NeuroNews: “As we continue to examine the value of endovascular therapy for acute ischaemic stroke, perhaps the most important contributory factor to this treatment’s success is patient selection. In the emergency room, imaging is fundamental to helping us understand the status of a patient’s brain following stroke, but, to date, there is no uniformly agreed-upon imaging technique to indicate which patients suffering from acute ischaemic stroke should receive endovascular therapy.
CT scans are used mostly to rule out bleeding and are thought to be relatively insensitive to changes resulting from acute ischaemia. The START trial is significant in that it is one of the first prospective, core-lab adjudicated, multicentre studies to prove that imaging can be used to quantify the amount of brain tissue affected by a stroke. In this study, that information proved useful in predicting which patients would benefit most from therapy. START should be followed up with larger studies that can produce additional data to validate these results.”