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CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes

This study is ongoing, but not recruiting participants.
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim Identifier:
First received: November 17, 2010
Last updated: April 19, 2017
Last verified: April 2017
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.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: linagliptin
Drug: glimepiride
Drug: linagliptin placebo
Drug: glimepride placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Time to first occurrence of any of the following adjudicated components of the primary composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI) or non-fatal stroke [ Time Frame: 432 weeks ]

Secondary Outcome Measures:
  • Time to first occurrence of any of the following adjudicated components of CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), non-fatal stroke or hospitalisation for unstable angina pectoris [ Time Frame: 432 weeks ]
  • Proportion of patients on study treatment at study end, that at Final Visit maintain glycemic control (HbA1c <= 7.0%) without need for rescue medication, without any moderate/severe hypoglycaemic episodes and without > 2% weight gain (from V6 on) [ Time Frame: 432 weeks ]
  • Occurence of any of the adjudicated components of the composite primary and composite first key secondary endpoint. [ Time Frame: 432 weeks ]
  • Transitions in albuminuria classes between baseline and Final visit. [ Time Frame: 432 weeks ]
  • Proportion of patients on study treatment at study end, that at Final Visit maintain glycaemic control (HbA1c <= 7.0%) without need for rescue medication and without > 2% weight gain (from V6 on) [ Time Frame: 432 weeks ]
  • Occurence of and time to composite endpoint of all CEC confirmed adjudicated events [ Time Frame: 432 weeks ]
  • Change from baseline to Final Visit in diabetes related laboratory parameters: HbA1c, fasting plasma glucose, Total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides, Creatinine, eGFR (MDRD formula), Urinary Albumin [ Time Frame: 432 weeks ]

Enrollment: 6072
Actual Study Start Date: October 26, 2010
Estimated Study Completion Date: March 1, 2019
Estimated Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: linagliptin
patient to receive linagliptin or glimepiride placebo overencapsulated tablet QD
Drug: linagliptin
linagliptin tablets 5mg QD
Drug: glimepride placebo
glimepiride placebo
Active Comparator: glimepiride 1-4 mg QD
patient to receive glimepiride 1-4 mg or linagliptin placebo tablet QD
Drug: glimepiride
glimepiride over-encapsulated tablet 1-4 mg QD
Drug: linagliptin placebo
linagliptin placebo


Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Type 2 diabetes
  2. Elevated glycosylated haemoglobin (HbA1c): 6.5 - 8.5%, inclusive, if treatment naïve or mono-/dual therapy with metformin and/or an alpha-glucosidase inhibitor; 6.5 - 7.5%, inclusive, if treatment with sulphonylurea/glinide in mono- or dual (with metformin OR an alpha-glucosidase inhibitor) therapy)
  3. Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age => 70 years OR two or more specified cardiovascular risk factor
  4. BMI =< 45kg/m²
  5. age between >= 40 and =< 85 years
  6. signed and dated written ICF
  7. stable anti-diabetic background for at least 8 wks before study start

Exclusion criteria:

  1. Type 1 diabetes
  2. Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, Glucagon-like peptide 1 (GLP-1) analogue/agonists, Dipeptidyl-peptidase IV (DPP-IV) inhibitors or any insulin) prior to informed consent (previous short term use of insulin (up to two weeks) is allowed if taken at least 8 weeks prior informed consent)
  3. treatment with any anti-obesity drug less than 3 months before ICF
  4. uncontrolled hyperglycemia
  5. previous or planned bariatric surgery or intervention
  6. current or planned system corticoid treatment
  7. change in thyroid hormones treatment
  8. acute liver disease or impaired hepatic function
  9. pre-planned coronary artery revascularization within 6 months of ICF
  10. known hypersensitivity to any of the components
  11. Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
  12. congestive heart failure class III or IV
  13. acute or chronic metabolic acidosis
  14. hereditary galactose intolerance
  15. alcohol or drug abuse
  16. participation in another trail with IMP given 2 months before IMP start
  17. pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control
  18. patients considered reliable by the investigator
  19. acute coronary syndrome =< 6 wks before ICF
  20. stroke or TIA =< 3 months prior to ICF
  Contacts and Locations
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Please refer to this study by its identifier: NCT01243424

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Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim Identifier: NCT01243424     History of Changes
Other Study ID Numbers: 1218.74
2009-013157-15 ( EudraCT Number: EudraCT )
Study First Received: November 17, 2010
Last Updated: April 19, 2017

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Immunosuppressive Agents
Immunologic Factors processed this record on May 22, 2017