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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01243424
First received: November 17, 2010
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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 occurence of any of the following adjudicated components of the primary composite endpoint: CV death, non-fatal MI (excluding silent MI), non-fatal stroke and hospitalisation for unstable angina pectoris [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first occurrence of any of the following adjudicated components of the composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal stroke, non-fatal MI (excluding silent MI) [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • 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: 400 weeks ] [ Designated as safety issue: No ]
  • Occurence of any of the adjudicated components of the composite primary and composite first key secondary endpoint. [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Transitions in albuminuria classes between baseline and Final visit. [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • 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: 400 weeks ] [ Designated as safety issue: No ]
  • Occurence of and time to composite endpoint of all CEC confirmed adjudicated events [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • 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), Albumin [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 6000
Study Start Date: October 2010
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (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

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Type 2 diabetes
  2. Elevated glycosylated heamoglobin (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

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. Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243424

  Show 610 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01243424     History of Changes
Other Study ID Numbers: 1218.74, 2009-013157-15
Study First Received: November 17, 2010
Last Updated: July 9, 2014
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Belgium: Federal Agency for Medicinal and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Comision Nacional De Investigacion Cientifica y Tecnologica
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Georgia: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Ireland: Irish Medicines Board
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Japan: Ministry of Health, Labor and Welfare
Malaysia: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Medsafe
Norway: Norwegian Medicines Agency
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Philippines: Bureau of Food and Drugs
Portugal: National Pharmacy and Medicines Institute
Romania: Ministry of Public Health
Russia: Pharmacological Committee, Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan : Food and Drug Administration
Tunisia: Ministry of Public Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
BI 1356
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014