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.
dc.contributor.author | Rosenstock, Julio | |
dc.contributor.author | Perkovic, Vlado | |
dc.contributor.author | Alexander, John H | |
dc.contributor.author | Cooper, Mark E | |
dc.contributor.author | Marx, Nikolaus | |
dc.contributor.author | Pencina, Michael J | |
dc.contributor.author | Toto, Robert D | |
dc.contributor.author | Wanner, Christoph | |
dc.contributor.author | Zinman, Bernard | |
dc.contributor.author | Baanstra, David | |
dc.contributor.author | Pfarr, Egon | |
dc.contributor.author | Mattheus, Michaela | |
dc.contributor.author | Broedl, Uli C | |
dc.contributor.author | Woerle, Hans-Juergen | |
dc.contributor.author | George, Jyothis T | |
dc.contributor.author | von Eynatten, Maximilian | |
dc.contributor.author | McGuire, Darren K | |
dc.contributor.author | CARMELINA® investigators | |
dc.date.accessioned | 2021-05-10T18:08:39Z | |
dc.date.available | 2021-05-10T18:08:39Z | |
dc.date.issued | 2018-03-14 | |
dc.date.updated | 2021-05-10T18:08:38Z | |
dc.description.abstract | 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® 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® 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® 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 α-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/m2, and eGFR 55 ± 25 mL/min/1.73 m2. A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m2 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® 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. Trial registration ClinicalTrials.gov identifier-NCT01897532; registered July 9, 2013. | |
dc.identifier | 10.1186/s12933-018-0682-3 | |
dc.identifier.issn | 1475-2840 | |
dc.identifier.issn | 1475-2840 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Cardiovascular diabetology | |
dc.relation.isversionof | 10.1186/s12933-018-0682-3 | |
dc.subject | CARMELINA® investigators | |
dc.subject | Kidney | |
dc.subject | Humans | |
dc.subject | Diabetic Nephropathies | |
dc.subject | Kidney Failure, Chronic | |
dc.subject | Cardiovascular Diseases | |
dc.subject | Diabetes Mellitus, Type 2 | |
dc.subject | Disease Progression | |
dc.subject | Blood Glucose | |
dc.subject | Glomerular Filtration Rate | |
dc.subject | Treatment Outcome | |
dc.subject | Cause of Death | |
dc.subject | Risk Factors | |
dc.subject | Double-Blind Method | |
dc.subject | Research Design | |
dc.subject | Time Factors | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Renal Insufficiency, Chronic | |
dc.subject | Dipeptidyl-Peptidase IV Inhibitors | |
dc.subject | Biomarkers | |
dc.subject | Linagliptin | |
dc.subject | Glycated Hemoglobin A | |
dc.title | 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. | |
dc.type | Journal article | |
duke.contributor.orcid | Alexander, John H|0000-0002-1444-2462 | |
duke.contributor.orcid | Pencina, Michael J|0000-0001-5798-8855|0000-0002-1968-2641 | |
pubs.begin-page | 39 | |
pubs.issue | 1 | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Duke Clinical Research Institute | |
pubs.organisational-group | Biostatistics & Bioinformatics | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Medicine, Cardiology | |
pubs.organisational-group | Medicine | |
pubs.organisational-group | Clinical Science Departments | |
pubs.publication-status | Published | |
pubs.volume | 17 |
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