Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease.

BACKGROUND: Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture. RESEARCH QUESTION: Can a nasal spray with Iota-Carrageenan be useful in the prophylaxis of COVID-19 in health care workers managing patients with COVID-19 disease? STUDY DESIGN AND METHODS: This is a pilot pragmatic multicenter, randomized, double-blind, placebo-controlled study assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients. Clinically healthy physicians, nurses, kinesiologists and other health care providers managing patients hospitalized for COVID-19 were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days. The primary end point was clinical COVID-19, as confirmed by reverse transcriptase polymerase chain reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322). RESULTS: A total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 differs significantly between subjects receiving the nasal spray with I-C (2 of 196 [1.0%]) and those receiving placebo (10 of 198 [5.0%]). Relative risk reduction: 79.8% (95% CI 5.3 to 95.4; p=0.03). Absolute risk reduction: 4% (95% CI 0.6 to 7.4). INTERPRETATION: In this pilot study a nasal spray with I-C showed significant efficacy in preventing COVID-19 in health care workers managing patients with COVID-19 disease. CLINICAL TRIALS REGISTRATION: NCT04521322.

A novel approach indirectly comparing benefit-risk balance across anti-thrombotic therapies in patients with atrial fibrillation.

BACKGROUND: Anti-thrombotic reduces thromboembolic events but increases bleeding in patients with atrial fibrillation (AF). We evaluated the benefit-risk of anti-platelet and anti-coagulant therapies, weighing these conflicting effects of treatment. METHODS: Randomized controlled trials in patients with AF were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through April 2014. We performed a stochastic multi-criteria acceptability analysis, which allowed us to compute a comprehensive benefit-risk profile. In the primary analysis, we used prior established rankings of mortality, intracranial haemorrhage, ischaemic stroke, myocardial infarction, major extracranial haemorrhage, and systemic embolism based on utility functions. In sensitivity analyses, we explored: (i) rankings based on costs, (ii) bleeding ranked higher than thromboembolism, and (iii) thromboembolism ranked higher than bleeding events. RESULTS: 100 913 patients (21 studies) were allocated to placebo/control, aspirin and/or clopidogrel, vitamin K antagonists (VKAs), or new oral anti-coagulants (NOACs). Based on utility, NOACs were better than VKA or anti-platelet therapy; dabigatran 150 mg was ranked highest (21% chance of being best). Ranked by cost, the 3 factor Xa inhibitors were very similar (16-18% chance of being best). When haemorrhagic events were weighted more than ischaemic events, edoxaban 30 mg was ranked higher (22%), while rivaroxaban (23%) was most preferred when ischaemic events were rated worse than haemorrhagic events. CONCLUSION: New oral anti-coagulants had a more favourable benefit-risk profile across a wide range of assumptions regarding the relative importance of clinical events. Differences between NOACs were modest and depended upon the order of ranking of clinical events.

Current and new oral antithrombotics in non-valvular atrial fibrillation: a network meta-analysis of 79 808 patients.

BACKGROUND: Antithrombotic therapy reduces stroke, embolism and mortality in patients with atrial fibrillation (AF); however, meta-analyses have focused on pairwise comparisons of treatments. OBJECTIVE: To synthesise the evidence from trials using a multiple treatment comparison methods thereby permitting a broader comparison across multiple therapies. DESIGN, SETTING, PATIENTS: Randomised controlled trials in patients with AF of antithrombotics were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through May 2012. We performed a random-effects model within a Bayesian framework using Markov Chain Monte Carlo simulation to calculate pooled OR and 95% credibility intervals (CrI). We also ranked therapies by their likelihood of leading to the best results for the outcomes. MAIN OUTCOME MEASURE: Multiple endpoints including stroke, embolism, death and bleeding. RESULTS: We identified 20 studies with 79 808 patients allocated to 8 treatments: ASA, ASA plus clopidogrel, vitamin K antagonists (VKAs), dabigatran 110 mg, dabigatran 150 mg, rivaroxaban, apixaban or placebo/control. Compared with placebo/control, dabigatran 150 mg was associated with the lowest risk of stroke (OR=0.25, 0.15-0.43), the composite of ischaemic stroke or systemic embolism (OR=0.26, 0.12-0.54) and mortality (OR=0.53, 0.28-0.88). ASA plus clopidogrel was associated with the highest risk of major bleeding (OR=3.65, 1.22-13.56). In simulated comparisons, the novel oral anticoagulants ranked better than VKA or antiplatelet therapies for prevention of stroke, ischaemic stroke or systemic embolism and mortality. CONCLUSIONS: In this network meta-analysis, novel oral anticoagulants were the most promising treatments to reduce stroke, stroke or systemic embolism, and all-cause mortality in patients with AF.

Novel oral anticoagulants in atrial fibrillation: a meta-analysis of large, randomized, controlled trials vs warfarin.

BACKGROUND: Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings. HYPOTHESIS: Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism. METHODS: Phase III randomized warfarin-controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all-cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel-Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed-effects (if homogenous) or random-effects models (if heterogeneous). RESULTS: In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.69-0.98; P = 0.03) and all-cause mortality (RR: 0.91; 95% CI: 0.85-0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74-0.94; P = 0.004) and all-cause mortality (RR: 0.91; 95% CI: 0.84 - 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta-analysis (drug class-outcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41-0.64; P < 0.0001). CONCLUSIONS: Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all-cause mortality. The benefit is largely due to fewer hemorrhagic strokes.