Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

Structured transition is associated with improved outcomes in diabetes

This study aimed to assess the effectiveness of a structured transition tool for the successful transitioning of young people (YP) with type 1 diabetes from paediatric to adult diabetic services. In a single-centre retrospective observational study, case notes were reviewed for YP with type 1 diabetes transitioning between paediatric and adult services between 2011–2014. YP were split into those who had participated in the ‘Ready Steady Go’ (RSG) structured transition programme as part of their routine care, and those who had not (RSG versus non-RSG). Between group comparisons were made for changes in objective measures before and after transfer to adult services including: glycated haemoglobin (HbA1c), non-high density lipoprotein (HDL) cholesterol concentrations and non-elective diabetes-related hospital admissions. Case note documentation of advice given during consultations was also reviewed. Data were available for 106 YP. Of these, 71 had participated in the RSG transition programme. Programme use was associated with lower non-elective, diabetes-related hospital admissions and lower non-HDL cholesterol concentrations compared with historical controls. The rise in HbA1c typically observed in YP during early adult life did not occur in the intervention group. No differences were observed in total cholesterol concentrations and body mass index. Trends towards higher rates of documentation of key topic discussions in the RSG group were significant for contraception and pregnancy. Due to the observed improvements in markers of metabolic and diabetes control, this study supports the role of a structured transition tool such as the ‘Ready Steady Go’ programme for YP with type 1 diabetes.</p

Tolvaptan treatment for severe neonatal autosomal-dominant polycystic kidney disease

Severe neonatal autosomal-dominant polycystic kidney disease (ADPKD) is rare and easily confused with recessive PKD. Managing such infants is difficult and often unsuccessful

COVID-19: experiences of lockdown and support needs in children and young adults with kidney conditions.

BACKGROUND During the initial COVID-19 pandemic, young United Kingdom (UK) kidney patients underwent lockdown and those with increased vulnerabilities socially isolated or 'shielded' at home. The experiences, information needs, decision-making and support needs of children and young adult (CYA) patients or their parents during this period is not well known. METHODS A UK-wide online survey co-produced with patients was conducted in May 2020 amongst CYA aged 12-30, or parents of children aged < 18 years with any long-term kidney condition. Participants answered qualitative open text alongside quantitative closed questions. Thematic content analysis using a three-stage coding process was conducted. RESULTS One-hundred and eighteen CYA (median age 21) and 197 parents of children (median age 10) responded. Predominant concerns from CYA were heightened vigilance about viral (68%) and kidney symptoms (77%) and detrimental impact on education or work opportunities (70%). Parents feared the virus more than CYA (71% vs. 40%), and had concerns that their child would catch the virus from them (64%) and would have an adverse impact on other children at home (65%). CYA thematic analysis revealed strong belief of becoming seriously ill if they contracted COVID-19; lost educational opportunities, socialisation and career development; and frustration with the public for not following social distancing rules. Positive outcomes included improved family relationships and community cohesion. Only a minority (14-21% CYA and 20-31% parents, merged questions) desired more support. Subgroup analysis identified greater negative psychological impact in the shielded group. CONCLUSIONS This survey demonstrates substantial concern and need for accurate tailored advice for CYA based on individualised risks to improve shared decision making