CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes - Full Text View

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:

Drug Information available for: Glimepiride Linagliptin

U.S. FDA Resources

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:

Type 2 diabetes
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)
Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age => 70 years OR two or more specified cardiovascular risk factor

Exclusion criteria:

Type 1 diabetes
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)
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

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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:	February 20, 2015
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 Tunisia: 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 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Glimepiride Linagliptin Anti-Arrhythmia Agents Cardiovascular Agents Dipeptidyl-Peptidase IV Inhibitors Enzyme Inhibitors	Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Hypoglycemic Agents Immunologic Factors Immunosuppressive Agents Incretins Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protease Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015