Diamed Clinical Research Services Pvt. Main Outcomes and Measures  Right of jury trial in civil cases. © 2020 American Medical Association. Davies 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. This is no lightweight trial-only software. The primary outcome occurred in 356 of 3023 participants (11.8%) in the linagliptin group and 362 of 3010 (12.0%) in the glimepiride group (HR, 0.98 [95.47% CI, 0.84-1.14]; P < .001 for noninferiority), meeting the noninferiority criterion but not superiority (P = .76). 2019 Dec 3;322(21):2138. Yalamanchi Hospitals & Research Centres Pvt Ltd. Edith Wolfson Medical Center, Diabetic Unit, Holon, The Chaim Sheba Medical Center Tel Hashomer, Policlinico Universitario Mater Domini, Universita di Catanzaro, Fondazione Centro San Raffaele del Monte Tabor, Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza, Daishinkai Medical Corporation Ookuma Hospital, Japan Community Health care Organization Nihonmatsu Hospital, Kanagawa Cardiovascular and Respiratory Center, Saitama Medical Cooperative Association Hanyu General Hospital, Keimyung University Dongsan Medical Center, National Health Insurance Service Ilsan Hospital, Seoul National University Bundang Hospital, Pusan National University Yangsan Hospital, Centro de Investigacion Cardiometabolica de Aguascalientes, Instituto Nacional de Cardiologia Ignacio Chavez, Unidad de Investigacion Clinica Cardiometabolica de Occident, Hospital Universitario Dr Jose Eleuterio Gonzalez, Noordwest Ziekenhuisgroep, location Den Helder, Bodø Legesenter AS, avd. Participants were screened from November 2010 through December 2012, with final follow-up on August 21, 2018. Percentage of patients with transition in albuminuria classes is presented as secondary endpoint. Primary End Point, Key Secondary Outcomes, and Other Secondary or Tertiary Cardiovascular End Points in a Study of the Effect of Linagliptin vs Glimepiride on Cardiovascular Outcomes in Patients With Type 2 Diabetes, Table 3. NORTH CAROLINA RACCOON FIELD TRIAL SURVEY REPORT 1987 THROUGH 2017 30th Anniversary N. C. WILDLIFE RESOURCES COMMISSION Colleen Olfenbuttel, Black Bear …  MA, Armstrong B. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. Additional sensitivity analyses are described in eAppendix 6 in Supplement 3. Site monitoring, data management, and data analysis were conducted by Boehringer Ingelheim. Group, Fullerton, California, United States, 92835, Long Beach, California, United States, 90807, Los Gatos, California, United States, 95032, North Hollywood, California, United States, 91606, Redondo Beach, California, United States, 90277, San Diego Sports Medicine and Family Health Center, San Diego, California, United States, 92120, San Ramon, California, United States, 94582, Tarzana, California, United States, 91356, Westlake Village, California, United States, 91361, Colorado Springs, Colorado, United States, 80909, Colorado Springs, Colorado, United States, 80920, Boca Raton, Florida, United States, 33433, Daytona Beach, Florida, United States, 32117, Fort Lauderdale, Florida, United States, 33309, Fort Lauderdale, Florida, United States, 33316, Jacksonville, Florida, United States, 32223, Jacksonville, Florida, United States, 32258, Jacksonville, Florida, United States, 32277, Lauderdale Lakes, Florida, United States, 33319, New Port Richey, Florida, United States, 34652, New Port Richey, Florida, United States, 34653, Palm Harbor, Florida, United States, 34684, Panama City, Florida, United States, 32401, Pembroke Pines, Florida, United States, 33024, Ponte Vedra Beach, Florida, United States, 32081, West Palm Beach, Florida, United States, 33401, Snellville, Georgia, United States, 30078, Bolingbrook, Illinois, United States, 60490, John H. Stroger Jr. Hospital of Cook Country, Evergreen Park, Illinois, United States, 60805, Brownsburg, Indiana, United States, 46112, Indianapolis, Indiana, United States, 46205, Indianapolis, Indiana, United States, 46254, Lexington, Kentucky, United States, 40503, Metairie, Louisiana, United States, 70006, Baltimore, Maryland, United States, 21234, Rockville, Maryland, United States, 20852, Tristan Medical Enterprises, PC dba Regeneris, North Attleboro, Massachusetts, United States, 02760, Kalamazoo, Michigan, United States, 49009, Saint Clair Shores, Michigan, United States, 48081, Sterling Heights, Michigan, United States, 48310, Traverse City, Michigan, United States, 49684, Minneapolis, Minnesota, United States, 55416, Biloxi, Mississippi, United States, 39531, Saint Louis, Missouri, United States, 63141, Clifton, New Jersey, United States, 07012, Elizabeth, New Jersey, United States, 07201, Elizabeth, New Jersey, United States, 07202, Albany Medical Center / Albany Medical College, Smithtown, New York, United States, 11787, Southgate Medical Group/ Southgate Medical Park, West Seneca, New York, United States, 14224, Asheville, North Carolina, United States, 28801, Burlington, North Carolina, United States, 27215, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States, 27517, Charlotte, North Carolina, United States, 28204, Charlotte, North Carolina, United States, 28205, Durham, North Carolina, United States, 27704, Elizabeth City, North Carolina, United States, 27909, Raleigh, North Carolina, United States, 27609, Shelby, North Carolina, United States, 28150, Statesville, North Carolina, United States, 28625, Wilmington, North Carolina, United States, 28401, Oklahoma City, Oklahoma, United States, 73103, Castlerock Clinical Research Consultants, LLC, Harleysville, Pennsylvania, United States, 19438, Detweiler Family Medicine & Associates, PC, Lansdale, Pennsylvania, United States, 19446, Philadelphia, Pennsylvania, United States, 19140, Warminster, Pennsylvania, United States, 18974, New England Center for Clinical Research, Inc, Cranston, Rhode Island, United States, 02920, Anderson, South Carolina, United States, 29621, Greenville, South Carolina, United States, 29601, Greer, South Carolina, United States, 29651, South Carolina Nephrology and Hypertension Center, Inc, Orangeburg, South Carolina, United States, 29118, Sumter, South Carolina, United States, 29150, University Diabetes and Endocrine Consultants, Chattanooga, Tennessee, United States, 37411, Tullahoma, Tennessee, United States, 37388, University of Texas Southwestern Medical Center, New Braunfels, Texas, United States, 78130, The Methodist Hospital d/b/a HMRI CCAT at Pearland, Northeast Clinical Research of San Antonio, LLC, Salt Lake City, Utah, United States, 84124, Federal Way, Washington, United States, 98003, Spokane, Washington, United States, 99204, Instituto de Investigaciones Clínicas de Bahía Blanca, Consultorios Asociados de Endocrinología e Invest Clínica, Instituto Cardiovascular de Corrientes Juana Francisca Cabra, Instituto de Investigaciones Clinicas de Rosario, Instituto de Hematología y Medicina Clínica Dr. Rubén Davoli, San Miguel de Tucumán, Argentina, T4000ICL, Centro de Investigaciones Clínicas del Litoral, Royal Brisbane & Women's Hospital-Endocrinology, Adelaide, South Australia, Australia, 5000, Hospital Universitário João de Barros Barreto, Centro de Estudos em Diabetes e Hipertensão, Irmandade Santa Casa de Misericordia de Porto Alegre, Instituto Estadual de Diabetes e Endocrinologia, Irmandade da Santa Casa de Misericórdia de São Paulo - IPEC - Instituto de Pesquisa Clínica, Instituto de Molestias Cardiovasculares - IMC, Univ.Multiprofile Hospital "Dr. Georgy Stranski" EAD, Pleven, Multiprofile Hospital for Active Treatment, Multiprofile Hospital for Active Treatment "Zaritza Johanna". Adverse events occurred in 2822 participants (93.4%) in the linagliptin group and 2856 (94.9%) in the glimepiride group, with 15 participants (0.5%) in the linagliptin group vs 16 (0.5%) in the glimepiride group with adjudicated-confirmed acute pancreatitis. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial JAMA . A total of 6042 participants were randomized, of whom 6033 received at least 1 dose of the study medication and were included in the primary outcome analysis (Figure 1). 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. Dr Espeland reported receiving consulting fees from Boehringer Ingelheim during the conduct of the study and grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Aging outside the submitted work. Randomized, double-blind, active-controlled, noninferiority trial, with participant screening from November 2010 to December 2012, conducted at 607 hospital and primary care sites in 43 countries involving 6042 participants. Jul 26, 2020 Contributor By : Gérard de Villiers Media PDF ID 1429503d north carolina trial practice forms thorps pdf Favorite eBook Reading carolina trial practice forms thorps by william l thorp april 1993 harrison co edition library  SE, The CAROLINA Trial. 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. For a clinician who works to achieve optimal outcomes, glucose-lowering therapies form part of a multifactorial intervention package. Accepted for Publication: August 15, 2019. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease.  HZ, Vethakkan Hazard ratio (HR) for hypoglycemia derived by Cox regression model analyses in patients treated with ≥1 dose of the study drug.  SK. CAROLINA is the only active-comparator cardiovascular outcome trial for a dipeptidyl peptidase-4 (DPP-4) inhibitor. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Moderate or severe hypoglycemia was defined as time to the first occurrence of symptomatic investigator-defined hypoglycemic adverse event with plasma glucose ≤70 mg/dL or a severe hypoglycemic adverse event. However, sulfonylureas are associated with increased risk of hypoglycemia1,3,5-7 and modest weight gain.1,5 In addition, there is an ongoing controversy regarding their long-term cardiovascular safety, based on early data from the University Group Diabetes Program in the 1960s8 and multiple observational and smaller studies indicating conflicting results.9,10. 1, Family Law, 2019 is a comprehensive legal reference created for North Carolina district court judges.  F, Paul Change from baseline to final visit in eGFR is presented as secondary diabetes-related endpoint. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. In this randomized noninferiority clinical trial that included 6033 participants followed up for a median of 6.3 years, the use of linagliptin compared with glimepiride added to usual care resulted in rates of the composite outcome (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) of 11.8% vs 12.0%. North Carolina Civil Trial Practice is North Carolina's only and leading practitioner treatise on civil trial practice and procedure (with application of the N.C. Rules of Evidence).  OE, Talk with your doctor and family members or friends about deciding to join a study. 2019 Jan 1;321(1):69-79. doi: 10.1001/jama.2018.18269. The secondary 4P-MACE outcome occurred in 398 of 3023 participants (13.2%) in the linagliptin group and 401 of 3010 (13.3%) in the glimepiride group (Table 2). Information provided by (Responsible Party): The aim of the study is to investigate the longterm impact on cardiovascular morbidity and mortality, relevant efficacy parameters (e.g., glycaemic parameters) and safety (e.g., weight and hypoglycaemia) of treatment with linagliptin in patients with type 2 diabetes at elevated cardiovascular risk receiving usual care, and compare outcome against glimepiride. Among adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median of 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome. Information on race and ethnicity was captured by investigators based on self-classification by trial participants as reported in the electronic case record form (fixed categories) following written informed consent. Median (quartile [Q] 1, Q3) follow-up was 6.2 (5.8, 6.6) years in the linagliptin group and 6.2 (5.6, 6.5) years in the glimepiride group. design and baseline characteristics of the cardiovascular outcome trial of linagliptin versus glimepiride in type 2 diabetes (CAROLINA). This randomized clinical trial compares the effects of the dipeptidyl peptidase 4 inhibitor linagliptin vs placebo plus usual care on cardiovascular (CV) and renal outcomes in adults with type 2 diabetes and high CV and renal risk. Median (Q1, Q3) study medication exposure was 5.9 (3.5, 6.4) years in the linagliptin group and 5.9 (3.4, 6.4) years in the glimepiride group (eAppendix 7 in Supplement 3). To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. 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. Modest weight gain was observed in the glimepiride group early in the study and maintained thereafter, with a weighted mean between-group difference of −1.54 kg (95% CI, −1.80 to −1.28; Figure 3B). North Carolina no longer has a speedy trial statute; the statutory provisions of Article 35 of Chapter 15A (G.S. (2013-300, s. Of 6042 participants randomized, 6033 (mean age, 64.0 years; 2414 [39.9%] women; mean glycated hemoglobin, 7.2%; median duration of diabetes, 6.3 years; 42% with macrovascular disease; 59% had undergone metformin monotherapy) were treated and analyzed.  JJ, Stringer Dis. The interim analyses were planned to be performed after 190 and 411 participants experienced a primary outcome event. The CARMELINA safety study for the dipeptidyl peptidase-4 inhibitor linagliptin not only shows no increase in CV, kidney, or safety events but also allays fears over a class heart failure effect.  N, Richards The first occurrence of any of the following Clinical Event Committee (CEC) confirmed adjudicated components of the primary composite endpoint: CV death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI (excluding silent MI), or nonfatal stroke is presented. 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. Detailed methods of the trial have been published previously.  J, Greene Influence of TCF7L2 gene variants on the therapeutic response to the dipeptidylpeptidase-4 inhibitor linagliptin. Composite primary end points in cardiovascular outcomes trials involving type 2 diabetes patients: should unstable angina be included in the primary end point? Investigator-reported cardiovascular outcome events, deaths, pancreatitis, and pancreatic cancer were prospectively captured and centrally adjudicated by clinical events committees masked to treatment assignment. Schramm 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. Categories of hypoglycemia were analyzed as “any,” “moderate or severe,” “severe,” or “leading to hospitalization” (for definitions of each categorization, see eAppendix 5 in Supplement 3). professionals, clinical trials personnel, clinical trials administrators, and public health -members are welcome to attend. 2019; 321: 69-79. SUMMARY OF CVOTS TO DATE Trial Designs Figure 1 displaysa timelineofcompleted and ongoing diabetes CVOTs, as well as several related trials that assessed CV outcomes but were not initiated as a di-rect result of the 2008 FDA guidance 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.  PC, Desai Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) is such a trial, ongoing since November 2010, and is currently the largest head-to-head CV outcome trial that involves a comparison of a SU (glimepiride) with a Get free access to newly published articles. The trial was conducted in accordance with the principles of the Declaration of Helsinki and the Harmonized Tripartite Guideline for Good Clinical Practice from the International Conference on Harmonisation and was approved by local authorities. McGuire This study has several limitations. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial JAMA. 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. Dr Johansen is employed by Boehringer Ingelheim, Norway. Currently, 4 large cardiovascular outcome trials have established the cardiovascular safety of DPP-4 inhibitors vs placebo in patients with type 2 diabetes at a high cardiovascular risk,20-23 including the Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA).23 In 2009, when the current trial was designed, sulfonylureas were the most commonly used second-line glucose-lowering agents after metformin, followed by DPP-4 inhibitors, but no head-to-head cardiovascular outcome trial existed for those 2 classes of medications. 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. Analysis based on hypoglycemic adverse events occurring between first study drug intake until 7 days after receiving the study drug for the final time.  CL. 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. Trials.  V, The third key secondary endpoint was a composite endpoint of treatment sustainability, defined as percentage of patients who were on trial medication at trial end, maintained glycaemic control (HbA1c ≤7.0%) without need for rescue medication, and without >2% weight gain during maintenance phase. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. Specifically, we defined the censoring date for the time-to-event analysis as the last date a patient was known to be free of an end point event, including any start dates of adverse event/outcome events, onset dates of adjudicated-confirmed events, date of percutaneous coronary intervention/coronary artery bypass grafting, or date of trial completion (defined as the latest of date of the last clinic visit, telephone call, or contact if lost to follow-up). Percentage of participants occurrence of at least one of the following adjudicated components of CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI) and non-fatal stroke is presented as secondary CV endpoint. Least square mean is adjusted mean. It provides summaries of North Carolina law governing cases Baseline data for the continuous glucose monitoring sub-study was collected and analyzed. The top-line results of the CAROLINA trial indicate that linagliptin is non-inferior to glimepiride. 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