IV.

Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

Level III, retrospective comparative study.

Objective: Transcarotid artery revascularization (TCAR) is a novel approach to carotid intervention that uses a direct carotid cut-down approach coupled with cerebral blood flow reversal to minimize embolic potential. The initial positive data with TCAR indicates that it may be an attractive alternative to trans-femoral carotid artery stenting and possibly carotid endarterectomy (CEA) for high-risk patients. The purpose of this study was to present 30-day and 1-year outcomes after treatment by TCAR and to compare these outcomes against a matched control group undergoing CEA at the same institutions.Methods: A retrospective review of all patients who underwent TCAR at four institutions between 2013 and 2017 was performed to evaluate the use of the ENROUTE Transcarotid Neuroprotection System (Silk Road Medical, Inc, Sunnyvale, Calif). TCAR patients had high-risk factors and were either enrolled in prospective trials or treated with a commercially available TCAR device after US Food and Drug Administration approval. Contemporaneous patients undergoing CEA at each institution were also reviewed. Patients were propensity matched in a 1:1 (CEA:TCAR) fashion with respect to preoperative comorbidities. Data were analyzed using statistical models with a P value of less than .05 considered significant. Individual and composite stroke, myocardial infarction, and death at 30 days and 1 year postoperatively were assessed.Results: Consecutive patients undergoing TCAR or CEA were identified (n ¼ 663) and compared. Patients undergoing the TCAR procedure (n ¼ 292) had higher rates of diabetes (P ¼ .01), hyperlipidemia (P ¼ .02), coronary artery disease (P < .01), and renal insufficiency (P < .01) compared with unmatched CEA patients (n ¼ 371). Stroke rates were similar at 30 days (1.0% TCAR vs 1.1% CEA) and 1 year (2.8% TCAR vs 3.0% CEA) in the unmatched groups. After propensity matching by baseline characteristics including gender, age, symptom status (36.3%, 35.3%) and diabetes, 292 TCAR patients were compared with 292 CEA patients. TCAR patients were more likely to be treated preoperative and postoperatively with clopidogrel (preoperatively, 82.2% vs 39.4% [P < .01]; postoperatively, 98.3% vs 36.0% [P < .01]) and statins (preoperatively, 88.0% vs 75.0% [P < .01]; postoperatively, 97.8% vs 78.8% [P < .01]). Stroke (1.0% TCAR vs 0.3% CEA; P ¼ .62) and death (0.3% TCAR vs 0.7% CEA; P ¼ NS) rates were similar at 30 days and comparable at 1 year (stroke, 2.8% vs 2.2% [P ¼ .79]; death 1.8% vs 4.5% [P ¼ .09]). The composite end point of stroke/death/myocardial infarction at 1 month postoperatively was 2.1% vs 1.7% (P ¼ NS). TCAR was associated with a decreased rate of cranial nerve injury (0.3% vs 3.8%; P ¼ .01).Conclusions: These early data suggest that patients undergoing TCAR, even those with high-risk comorbidities, achieve broadly similar outcomes compared with patients undergoing CEA while mitigating cranial nerve injury. Further comparative studies are warranted.