RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

AIMS: To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS). METHODS: In a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia. RESULTS: Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95% CI: 1.13–4.60, P = 0.022). Using placebo as reference (bleeding rate 3.1%), there was a dose–response relationship (P = 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3% for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P = 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity. CONCLUSIONS: Darexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial. ClinicalTrials.gov Identifier: NCT0099429

Developing a holistic risk management plan in mitigating flooding risks for buildings adjacent to the Swan River in Perth, Western Australia

AbstractClimate change as a major issue in the 21st century has seen the rise of the sea level and worse storm surges. This has impacted on the further distribution of salinity and flooding of low laying areas even in further inland areas. As the consequence, buildings in the proximity of riverbanks are left susceptible to potential damages and shortened life cycles. Thus, there is a real need to change the way buildings in these areas to be designed and how risk of damages can be mitigated and managed. The city of Perth in Western Australia, like many other cities around the world, is laying on the riverbank of a large river, the Swan River. As the population of Perth increases dramatically, it will become important to ensure sustainability of its buildings to support the ever growing populations and hence its needs. There are myriads of approaches in mitigating and managing these risks. This research project aims to investigate the contemporary risk management practices in mitigating flooding risk in buildings adjacent to the Swan River and bring them together as a holistic risk management approach. The findings of this research can be proposed to the Western Australian government to assist them in developing further policies in ensuring sustainable buildings fit for the future. At this point of writing, the research project is on its early stage of conducting literature review and designing the research methodology. It is intended to conduct a pilot survey, followed by case study approach of contemporary buildings adjacent to the Swan River to contextualize the research. This paper presents the current progress of this research