Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Clinical handover within the emergency care pathway and the potential risks of clinical handover failure (ECHO): primary research

Background and objectives: Handover and communication failures are a recognised threat to patient safety. Handover in emergency care is a particularly vulnerable activity owing to the high-risk context and overcrowded conditions. In addition, handover frequently takes place across the boundaries of organisations that have different goals and motivations, and that exhibit different local cultures and behaviours. This study aimed to explore the risks associated with handover failure in the emergency care pathway, and to identify organisational factors that impact on the quality of handover. Methods: Three NHS emergency care pathways were studied. The study used a qualitative design. Risks were explored in nine focus group-based risk analysis sessions using failure mode and effects analysis (FMEA). A total of 270 handovers between ambulance and the emergency department (ED), and the ED and acute medicine were audio-recorded, transcribed and analysed using conversation analysis. Organisational factors were explored through thematic analysis of semistructured interviews with a purposive convenience sample of 39 staff across the three pathways. Results: Handover can serve different functions, such as management of capacity and demand, transfer of responsibility and delegation of aspects of care, communication of different types of information, and the prioritisation of patients or highlighting of specific aspects of their care. Many of the identified handover failure modes are linked causally to capacity and patient flow issues. Across the sites, resuscitation handovers lasted between 38 seconds and 4 minutes, handovers for patients with major injuries lasted between 30 seconds and 6 minutes, and referrals to acute medicine lasted between 1 minute and approximately 7 minutes. Only between 1.5% and 5% of handover communication content related to the communication of social issues. Interview participants described a range of tensions inherent in handover that require dynamic trade-offs. These are related to documentation, the verbal communication, the transfer of responsibility and the different goals and motivations that a handover may serve. Participants also described the management of flow of patients and of information across organisational boundaries as one of the most important factors influencing the quality of handover. This includes management of patient flows in and out of departments, the influence of time-related performance targets, and the collaboration between organisations and departments. The two themes are related. The management of patient flow influences the way trade-offs around inner tensions are made, and, on the other hand, one of the goals of handover is ensuring adequate management of patient flows. Conclusions: The research findings suggest that handover should be understood as a sociotechnical activity embedded in clinical and organisational practice. Capacity, patient flow and national targets, and the quality of handover are intricately related, and should be addressed together. Improvement efforts should focus on providing practitioners with flexibility to make trade-offs in order to resolve tensions inherent in handover. Collaborative holistic system analysis and greater cultural awareness and collaboration across organisations should be pursued. Funding: The National Institute for Health Research Health Services and Delivery Research programme