TY - JOUR A1 - Rosenstock, Julio A1 - Perkovic, Vlado A1 - Alexander, John H. A1 - Cooper, Mark E. A1 - Marx, Nikolaus A1 - Pencina, Michael J. A1 - Toto, Robert D. A1 - Wanner, Christoph A1 - Zinman, Bernard A1 - Baanstra, David A1 - Pfarr, Egon A1 - Mattheus, Michaela A1 - Broedl, Uli C. A1 - Woerle, Hans-Jürgen A1 - George, Jyothis T. A1 - von Eynatten, Maximilian A1 - McGuire, Darren K. T1 - Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin - (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk JF - Cardiovascular Diabetology N2 - Background: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA (R) trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. Methods: CARMELINA (R) is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5-10.0% (48-86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, >= 40% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA (R) was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided a-level of 2.5%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure. Results: Between July 2013 and August 2016, 6980 patients were randomized and took >= 1 dose of study drug (40.6, 33.1, 16.9, and 9.4% from Europe, South America, North America, and Asia, respectively). At baseline, mean +/- SD age was 65.8 +/- 9.1 years, HbA1c 7.9 +/- 1.0%, BMI 31.3 +/- 5.3 kg/m(2), and eGFR 55 +/- 25 mL/min/1.73 m(2). A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m(2) or macroalbuminuria [albumin-to-creatinine ratio > 300 mg/g]) and 3990 patients (57.2%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5%]) and macroalbuminuria (n = 2691 [38.6%]) were common. Conclusions: CARMELINA (R) will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk. KW - Diabetes mellitus KW - type 2 KW - Cardiovascular diseases KW - Diabetic nephropathies KW - Dipeptidyl-peptidase IV inhibitors KW - Linagliptin KW - Clinical trial KW - phase IV KW - Research design KW - Treatment outcome Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226996 VL - 17 ER - TY - JOUR A1 - Perkovic, Vlado A1 - Agarwal, Rajiv A1 - Fioretto, Paola A1 - Hemmelgarn, Brenda R. A1 - Levin, Adeera A1 - Thomas, Merlin C. A1 - Wanner, Christoph A1 - Kasiske, Bertram L. A1 - Wheeler, David C. A1 - Groop, Per-Henrik T1 - Management of patients with diabetes and CKD: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) controversies conference JF - Kidney International N2 - The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population. KW - stage renal-disease KW - converting enzyme-inhibition KW - dietary sodium restriction KW - intensive glucose control KW - albumin excretion rate KW - blood pressure KW - cardiovascular outcomes KW - randomized trial KW - glycemic control KW - receptor KW - antidiabetic agents KW - cardiovascular disease KW - chronic kidney disease KW - diabetes KW - renoprotection KW - antagonist Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186599 VL - 90 IS - 6 ER -