Dual-Layer Detector Cone-Beam CT Angiography for Stroke Assessment: First-in-Human Results (the Next Generation X-ray Imaging System Trial).

BACKGROUND AND PURPOSE: In patients with stroke, IV cone-beam CTA in the angiography suite could be an alternative to CTA to shorten the door-to-thrombectomy time. However, image quality in cone-beam CTA is typically limited by artifacts. This study evaluated a prototype dual-layer detector cone-beam CT angiography versus CTA in patients with stroke. MATERIALS AND METHODS: A prospective, single-center trial enrolled consecutive patients with ischemic or hemorrhagic stroke on initial CT. Intracranial arterial segment vessel conspicuity and artifact presence were evaluated on dual-layer cone-beam CTA 70-keV virtual monoenergetic images and CTA. Eleven predetermined vessel segments were matched for every patient. Twelve patients were necessary to show noninferiority to CTA. Noninferiority was determined by the exact binomial test; the 1-sided lower performance boundary was prospectively set to 80% (98.75% CI). RESULTS: Twenty-one patients had matched image sets (mean age, 72 years). After excluding examinations with movement or contrast media injection issues, all readers individually considered dual-layer cone-beam CT angiography noninferior to CTA (CI boundary, 93%, 84%, 80%, respectively) when evaluating arteries relevant in candidates for intracranial thrombectomy. Artifacts were more prevalent compared with CTA. The majority assessment rated each individual segment except M1 as having noninferior conspicuity compared with CTA. CONCLUSIONS: In a single-center stroke setting, dual-layer detector cone-beam CTA virtual monoenergetic images are noninferior to CTA under certain conditions. Notably, the prototype is hampered by a long scan time and is not capable of contrast media bolus tracking. After excluding examinations with such scan issues, readers considered dual-layer detector cone-beam CTA noninferior to CTA, despite more artifacts.

Key design elements of successful acute ischemic stroke treatment trials.

PURPOSE: We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics. METHOD: We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review. FINDINGS: Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11). DISCUSSION: Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden. CONCLUSION: The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.

Intravenous thrombolysis in stroke mimics: results from the SITS International Stroke Thrombolysis Register.

BACKGROUND AND PURPOSE: Patients with stroke mimics (SM), i.e. conditions with stroke-like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions. METHODS: We included IVT-treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003-2017, examined with magnetic resonance imaging 22-36 h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST), Second European Co-operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3 months. RESULTS: Of 10 436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5-10) vs. 8 (5-14), P < 0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% (P < 0.001), SICH NINDS in 0.5% vs. 3.9% (P < 0.001), SICH ECASS II in 0.2% vs. 2.1% (P = 0.007) and SICH SITS-MOST in 0% vs. 0.5% (P = 0.28). Modified Rankin Scale score 0-1 at 3 months was present in 84.1% vs. 57.7% (P < 0.001) and death within 3 months in 2.6% vs. 5.4% (P = 0.028) of mimics and stroke patients, respectively. CONCLUSIONS: This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.