D-JRA2.3 Smart Grid Simulation Environment

This report summarizes the work conducted within ERIGrid related to an integrated simulation environment for large-scale systems.The main goal of the JRA2 is to develop advanced simulation-based tools and methods to validate Smart Grid scenarios, configurations and applications in con-text of co-simulation. The work done in D-JRA2.1 involved assessment of specialized simulation packages for Smart Grids and to develop tools to couple these simulation packages for co-simulation. New tools and models were also developed as some of the existing tools were not sufficient enough to achieve the appropriate couplings. In D-JRA2.2 co-simulation-based assessment methods were developed to compare the performance between monolithic and co-simulations. In D-JRA2.3 we aim to combine all the work done under WP JRA2 to present an integrated simulation package that can be applied to Large Scale systems. The assessment methods developed in D-JRA2.2 have been tested initially in small systems to measure the performance and identify possible flaws. How-ever, the complexity increases significantly in large scale realistic systems. This report documents the challenges faced when the systems and their models grow larger (i.e., upscaled) and how different large scale specific phenomena and issues were identified. After the identification of the challenges, the assessment methods were modified and packaged into an in-tegrated simulation environment which can be used for scaled out systems. The simulation pack-ages are provided as an addendum along with this report while their details are concisely docu-mented in this report.Intelligent Electrical Power Grid

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics