Update on the TACIT Trial
New endpoints and new data have made TACIT even more critical.
Endovascular Today: How has the Transatlantic Asymptomatic Carotid Intervention Trial (TACIT) changed in the past year?
Dr. Rundback: We have submitted to the National Institute of Neurological Disorders and Stroke, and feedback from council review indicated that we need to make revisions to the protocol. We are undertaking those revisions with the intention to resubmit for the October NIH deadline, either as an RO1 application, or possibly as a planning grant. In the interim, we are pursuing meetings with pharmaceutical partners for additional support as well as some device companies.
The executive committee has made some changes to the protocol and is redefining TACIT as a two-arm trial (Table 1). This change is based on the fact that early data from CREST and other studies suggest that there is no difference between endarterectomy and stenting in asymptomatic patients. Given the high cost and burden of enrolling an additional cohort of surgical patients, the executive committee has decided that this will be a two-arm trial comparing stenting using distal protection (with commercially available devices) versus best medical therapy alone with a regimented, rigorously defined and targeted medical therapeutic plan in both arms of the study.
Endovascular Today: How has the primary outcome measure changed?
Dr. Rundback: We have come to better understand some of the clinically relevant measures of carotid interventions so that the new outcome will reflect these new insights. The primary TACIT outcome is now a composite of 30-day mortality, all strokes within the 5-year study period, and a component of neurocognitive function measuring a reduction in neurocognitive decline–what we are calling vascular dementia or vascular depression using predominantly depression scales.
Endovascular Today: Is CASPR a component of TACIT? Or, is TACIT including a neurocognitive section because of the CASPR results?
Dr. Rundback: The CASPR trial unequivocally demonstrated in approximately 50 patients that there is neurocognitive improvement after stenting, so we are using those preliminary data as supportive material for the new TACIT application. Rodney Raabe, MD, is heading up the neurocognitive group for TACIT, and he is working closely with his committee to structure a battery of tests that will be used to develop the neurocognitive outcome measure.
Endovascular Today: How will this affect the primary and secondary endpoints?
Dr. Rundback: TACIT will now have a neurocognitive component–vascular depression–within the primary endpoint and a detailed neurocognitive battery as a secondary endpoint. In fact, within the secondary endpoints, one of the most exciting aspects is a detailed and comprehensive analysis of each of the components of neurocognitive function. Neuropsychological assessments will include a battery of tests that look at cognitive speed, depression, dementia scales, verbal function, and memory. Each of these components will be independently and collectively examined. The secondary endpoints will also include a detailed quality-of-life and cost-effectiveness analysis, which is important because this has not been done at all in patients being considered for revascularization of asymptomatic disease.
Another unique secondary endpoint in TACIT is plaque characterization. Michael Jaff, DO, an executive committee member (Table 2), will be working with Dr. Giorgio Biasi in Milan, Italy, to lead a group doing detailed core lab assessments of ultrasound plaque features. As you may know, the ICAROS trial in Europe suggested that there are plaque features that are predictive of stroke. We are going to look at a detailed subset evaluation of plaque characteristics as a predictor of procedural stroke, as well as de novo stroke risk in patients who do not undergo revascularization, to optimally determine the best candidates for treatment.
Endovascular Today: How many sites are currently enrolled, and how many do you anticipate?
Dr. Rundback: We already have 130 sites that have completed primary surveys for participation in the trial, more or less equally divided between the US and the EU. Altogether, approximately 2,400 patients will be enrolled in TACIT.
Endovascular Today: Was there a controversy regarding TACIT at Charing Cross this year?
Dr. Rundback: Dr. Barry Katzen had a debate with Alison Halliday, MD. Dr. Halliday is pursuing a very CREST-like trial, ACST 2, which is looking at stenting versus endarterectomy. The ACST group does not believe that there is clinical equipoise between medical therapy and revascularization in asymptomatic patients with high-grade stenoses, but the reality is that recent data suggest that statins improve the results of medical therapy alone and may have a large impact on primary stroke prevention, as well as reduce the occurrence of strokes after revascularization.1 Rigorous medical therapy has not been evaluated in other trials, including ACST 1, which overall had a 70% compliance with the recommended medical regimen, but with less than half of the patients receiving statins during the conduct of the trial. This is a critically important point that is reflected in the fact that the neurology community has not embraced stenting in asymptomatic patients and largely does not refer patients with asymptomatic CAS for revascularization. Since asymptomatic patients comprise the largest population with carotid disease, there is a huge clinical gap that needs to be overcome to finally define the role of stenting in these patients.
John H. Rundback, MD, is Medical Director, Interventional Institute, Holy Name Hospital, in Teaneck, New Jersey, and Associate Professor of Clinical Radiology, Columbia University College of Physicians and Surgeons, in New York. Dr. Rundback may be reached at email@example.com.