KK, to download free article PDFs, Tradjenta (linagliptin) tablets prescribing information. Death from any cause was not significantly different between participants in the linagliptin (308 of 3023 [10.2%]) and glimepiride (336 of 3010 [11.2%]) groups (HR, 0.91 [95% CI, 0.78-1.06]; Figure 2B), with an HR for cardiovascular death of 1.00 (95% CI, 0.81-1.24; Figure 2C) and an HR for noncardiovascular death of 0.82 (95% CI, 0.66-1.03; Figure 2D; eAppendix 9 in Supplement 3). The top-line results of the CAROLINA trial indicate that linagliptin is non-inferior to glimepiride. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01243424. Objective/Methods Dr. Rosenstock: CAROLINA is a randomized, double-blind, active-controlled, multicenter clinical trial designed to test the cardiovascular safety of a DDP-4 inhibitor (linagliptin) versus a sulfonylurea (glimepiride). north carolina civil trial practice Oct 13, 2020 Posted By Kyotaro Nishimura Publishing TEXT ID 935c6e5b Online PDF Ebook Epub Library page calendar with 10 cases on each page and see notes by the trial court administrator such Center for Drug Evaluation and Research. CAROLINA is the longest cardiovascular safety outcomes trial to date, and it’s the only one with a head-to-head a… List of predefined endpoints beyond those listed in the trial statistical analysis plan. The median duration of follow-up was 6.3 years. The current study reaffirms clinical recommendations to choose an oral agent after metformin based on proven cardiovascular benefit,1,2 which none of the agents studied provide. Occurrence of accelerated cognitive decline based on regression based index (RBI) score at end of follow-up (a dichotomous outcome measure; presence or absence of accelerated cognitive decline) is Cognition sub-study endpoint. Talk with your doctor and family members or friends about deciding to join a study. Home Archives Profile Subscribe Medicare will no longer cover hospital mapractice costs and could eliminate liens Percent disease incidence (%) of black shank assed in the fungicide rotation trial in Wilson Co. Higher the number (%) means more disease, in this case treatment 2 compound by Orondis Gold at transplant water (10 fl oz/A), Ridomil Gold at first cultivation (16 Diamed Clinical Research Services Pvt. Change from baseline to final visit in creatinine is presented as secondary diabetes-related endpoint. In this long-term, multicenter, double-blind, randomized, active comparator trial of individuals with relatively early type 2 diabetes at elevated cardiovascular risk, linagliptin was noninferior to glimepiride for the combined 3P-MACE end point. Materials and Methods: People aged 40 to 85 years with relatively early type 2 dia-betes, inadequate glycaemic control and elevated CV risk were randomly assigned to linagliptin 5 mg or glimepiride 1 to 4 mg. O’Brien TR. Call Number: KFS2328 .A52 2008 Publication Date: 2008 Participants who prematurely discontinued the study medication were followed up for ascertainment of cardiovascular events, mortality, adverse events, and other end points. Change from baseline to final visit in HbA1c is presented as secondary diabetes-related endpoint. This cohort study uses data from the National Veterans Health Administration, Medicare, Medicaid, and National Death Index to compare major adverse cardiovascular events among patients with diabetes and reduced kidney function who continued treatment with metformin or sulfonylurea. The trial design has been previously published. Accepted for Publication: August 15, 2019. 2019 Jan;42(1):e1-e3. design and baseline characteristics of the cardiovascular outcome trial of linagliptin versus glimepiride in type 2 diabetes (CAROLINA). EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes: II: mortality results. Appellate Procedure North Carolina Rules of Appellate Procedure Forms Trial Procedure General Rules of Practice for the Superior and In addition, we prespecified several tertiary cardiovascular end points (ie, occurrence of and time to first occurrence of each of the confirmed adjudicated end points), tertiary diabetes-related end points (eg, change of laboratory parameters from baseline to each planned week, hypoglycemia occurrence, change in weight and rescue medication use), and other end points (including noncardiovascular death and adverse events). Rationale and design of the CAROLINA® - cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus. Introduction of additional glucose-lowering therapies occurred in similar proportions across study groups, with a pattern of shorter time to introduction in the linagliptin group compared with the glimepiride group (eAppendix 12 in Supplement 3). publication in the North Carolina Court of Appeals Reports. The median duration of follow-up was 6.3 years. Linagliptin is a selective, once-daily, DPP-4 inhibitor approved for glycemic management of type 2 diabetes, with low risk of hypoglycemia and weight neutrality.11 To date, no head-to-head trial has compared the long-term effect of these agents on cardiovascular morbidity and mortality or glucose-lowering efficacy in patients with type 2 diabetes. Except for the prespecified 5-step hierarchical testing strategy, there was no adjustment for multiple comparisons and, therefore, the results of subgroup analyses and other end points should be interpreted as exploratory. 511, 523 (2011) (trial court properly refused to take judicial notice of contents of Federal Register that had “no relevance to the North Carolina crime of driving while license revoked”); State v. Baskin, 190 N A consistently lower hypoglycemia risk was observed in the linagliptin group than in the glimepiride group across all subgroups analyzed (eAppendix 16 in Supplement 3). Time to first occurrence of 4P-MACE was hierarchically evaluated as the first of the prespecified key secondary end points, followed by analyses of the proportion of patients receiving treatment and maintaining HbA1c of less than or equal to 7.0% at the final follow-up visit who (1) were without the need for rescue medication, did not have any moderate/severe hypoglycemic episodes, and did not have greater than 2% weight gain or (2) were without the need for rescue medication and did not have greater than 2% weight gain between the end of titration and final visit. Objective McGuire et al. MJ, D’Alessio T, Severe hypoglycemia was defined as an event requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. High cardiovascular risk was defined as (1) established atherosclerotic cardiovascular disease (documented ischemic heart disease, cerebrovascular disease, or peripheral artery disease), (2) multiple risk factors (at least 2 of the following: type 2 diabetes duration >10 years, systolic blood pressure >140 mm Hg [or receiving at least 1 blood pressure–lowering treatment], current smoker, low-density lipoprotein cholesterol ≥135 mg/dL [3.5 mmol/L], or receiving lipid-lowering treatment), (3) age at least 70 years, and (4) evidence of microvascular complications (impaired kidney function [estimated glomerular filtration rate of 30-59 mL/min/1.73 m2], urine albumin/creatinine ratio ≥30 μg/mg, or proliferative retinopathy). Leyshon, 211 N.C. App. For the purposes of the raccoon field trial survey, North Carolina is divided into 3 furbearer Data Sharing Statement: See Supplement 5. FDA guidance on antihyperglyacemic therapies for type 2 diabetes: one decade later. This is no lightweight trial-only software. Least square mean is adjusted mean. A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk. The South Carolina Triple P System Population Trial to Prevent Child Maltreatment: Seven Reasons to be Sceptical about the Study Results Members of Leuven Biostatistics and Statistical Bioinformatics Centre, Belgium, conducted an independent statistical analysis of the cardiovascular and mortality outcomes (eAppendix 2 in Supplement 3). doi: 10.2337/DC18-0914. OE, Meeting expectations to exclude a CV risk margin of 1.3. In all controversies at law respecting property, the ancient mode of trial by jury is one of the Investigators were encouraged to monitor and use additional medication for glycemic control per local guidelines, particularly if HbA1c was greater than 7.5% after the end of the titration phase. It provides summaries of North Carolina law governing cases The 95.47% CI for the primary end point was adjusted for multiplicity due to 2 interim analyses and change of the primary end point. Right of jury trial … 2018 Jan 15;18(1):7. doi: 10.1186/s12883-018-1014-7. The upper limit of the 95.47% CI of the hazard ratio was 1.14, which met the noninferiority criterion of a hazard ratio of less than 1.3. Get free access to newly published articles. Trial Registration Listing a study does not mean it has been evaluated by the U.S. Federal Government. (Clinical Trial). (b) Demand. 2019 Sep 19;322(12):1155-1166. doi: 10.1001/jama.2019.13772. 2019;322(12):1155–1166. J, Elevated cardiovascular risk was defined as documented atherosclerotic cardiovascular disease, multiple cardiovascular risk factors, aged at least 70 years, and evidence of microvascular complications. Rules of practice, procedure, and conduct adopted by the Supreme Court of North Carolina. Group Information: The trial was designed by independent academic investigators along with clinician scientists employed by Boehringer Ingelheim, the latter as nonvoting members of the steering committee that oversaw the trial. For similar provisions in Constitution of 1868, see Const 1868, Art 1, … Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®). Endocrinology & Metab. North Carolina Trial Judges' Bench Book, District Court, Vol. CR. Zimdahl Military Medical Academy, Clin. et al; TECOS Study Group. As prespecified, data were included up to the planned week that could theoretically be achieved by all patients. This trial assessed cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in patients with relatively early type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease. There was no between-group imbalance in adjudication-confirmed pancreatitis or pancreatic cancer. Insulin therapy or previous exposure to DPP-4 inhibitors, glucagonlike peptide-1 receptor agonists, or thiazolidinediones were exclusion criteria, as was New York Heart Association class III to IV heart failure (eAppendix 3 and 4 in Supplement 3). CAROLINA® (CARdiovascular Outcome study of LINAgliptin versus glimepiride in patients with type 2 diabetes) is a multi-national, randomised, double-blind, active-controlled clinical trial that involved 6,033 adults with type 2 diabetes from 43 countries at more than 600 sites observed for a median duration of more than 6 years. The term "active participant" as used herein includes each person who owns or handles dogs, carries a firearm, or is a member of an organized group engaged in the conduct of a field trial, but does AS, Coresh E, Balijepalli Green However, medication exposure was comparable between study groups, and annualized discontinuation rates are in line with most of the contemporary cardiovascular outcome trials of glucose-lowering therapies, all of which were of shorter duration.17,18,20,21,24 Furthermore, analyses limited to events that were occurring while patients were receiving study medication yielded results consistent with the primary analysis. chapter opening 1-5 Table of Contents Chapter 1: Spousal Agreements Percentage of patients with transition in albuminuria classes is presented as secondary endpoint. Enrollment, Randomization, and Follow-up of Participants in a Study of the Effect of Linagliptin vs Glimepiride on Cardiovascular Outcomes in Patients With Type 2 Diabetes, Figure 2. Compared with glimepiride, the use of linagliptin demonstrated noninferiority with regard to the risk of major cardiovascular events over a median of 6.3 years in patients with relatively early type 2 diabetes and elevated cardiovascular risk. CAROLINA ® is the only active-comparator cardiovascular outcome trial for a dipeptidyl peptidase-4 (DPP-4) inhibitor. Jury trial of right. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. Importance The distribution of causes of noncardiovascular death in the linagliptin group (139 of 3023 participants [4.6%]) and the glimepiride group (168 of 3010 participants [5.6%]) is provided in eAppendix 10 in Supplement 3. The Final Visit value referred to the last value obtained on-treatment. The primary outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with the aim to establish noninferiority of linagliptin vs glimepiride, defined by the upper limit of the 2-sided 95.47% CI for the hazard ratio (HR) of linagliptin relative to glimepiride of less than 1.3. WB, Cannon North Carolina Trial Judges' Bench Book District Court, Volume 1 Family Law Summary Table of Contents (All chapters updated through 9/20/2018) blank is page intentionally left blank. Baseline data for the continuous glucose monitoring sub-study was collected and analyzed. 2013 Jul;8(4):345-349. doi: 10.1586/17446651.2013.811849. SR, Hussein Hypoglycemia risk was increased across the entire dose range for the glimepiride group (eAppendix 15 in Supplement 3). Stavanger, Instituto Delgado de Investigacion Medica, Centro de Investigaciones Médicas METABOLICARE SAC, Centro De Especialidades Medicas Santa Maria S.A.C, CHUC - Centro Hospitalar e Universitário de Coimbra, EPE, Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã, Centro Hospitalar de Entre o Douro e Vouga, E.P.E. Conflict of Interest Disclosure: Dr Rosenstock reported serving on scientific advisory boards and received honoraria and consulting fees from Eli Lilly, Sanofi, Novo Nordisk, Janssen, AstraZeneca, Boehringer Ingelheim, and Intarcia and receiving grants/research support from Merck, Pfizer, Sanofi, Novo Nordisk, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Genentech, Janssen, Lexicon, Boehringer Ingelheim, and Intarcia. GH, Vaag AGENDA (September 21, 2019) 7:45 Registration The study protocol was approved by the institutional review board or independent ethics committee from each site, and all patients provided written informed consent; the trial protocol is available is Supplement 1 and the statistical analysis plan in Supplement 2. Rates of investigator-reported hypoglycemia were 2.3 events per 100 participant-years in the linagliptin group and 11.1 per 100 participant-years in the glimepiride group (incidence rate difference, −8.7 [95% CI, −9.4 to −8.0]; HR, 0.23 [95% CI, 0.21-0.26]; P < .001); rates of moderate or severe hypoglycemic events were 1.4 per 100 participant-years in the linagliptin group and 8.4 per 100 participant-years in the glimepiride group (incidence rate difference, −7.0 [95% CI, −7.6 to −6.5]; HR, 0.18 [95% CI, 0.15-0.21]; P < .001; Figure 4). 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