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. The CAROLINA Trial. - CAROLINA
- Conditions
- Patients with documented diagnosis of T2DM with insufficient glycaemic control and at high risk of CV events prior to informed consent can be enrolled in the study.MedDRA version: 9.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus
- Registration Number
- EUCTR2009-013157-15-FI
- Lead Sponsor
- Boehringer Ingelheim Pharma GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 6000
Documented diagnosis of T2DM and concurrently 1) insufficient glycaemic control and 2) a high risk of CV events prior to informed consent
1)Insufficient glycaemic control (at Visit 1a) defined as:
a) HbA1c 6.5 - 8.5% (48 - 69 mmol/mol) while patient is treatment naïve or treated with:
- metformin monotherapy, or
- alpha-glucosidase inhibitor monotherapy (e.g. acarbose, voglibose), or
- metformin + alpha-glucosidase inhibitor (e.g. acarbose, voglibose), or
b) HbA1c 6.5 - 7.5% (48 - 58 mmol/mol) while patient is treated with
- sulphonylurea (SU) monotherapy, or
- glinide monotherapy (e.g. repaglinide, nateglinide), or
- metformin + sulphonylurea (combination maximal up to 5 years), or
- metformin + glinide (combination maximal up to 5 years)
2)High risk of CV events defined as any one (or more) of A), B), C) or D):
A) Previous Vascular Disease:
- Myocardial infarction (> 6 weeks prior to informed consent)
- Documented coronary artery disease (=50% luminal diameter narrowing of left main coronary artery or in at least two major coronary arteries in angiogram)
-Percutaneous Coronary Intervention (PCI) > 6 weeks prior informed consent
-Coronary Artery By-pass Grafting (CABG) > 4 years prior to informed consent or with recurrent angina following surgery
-Ischemic or hemorrhagic stroke (> 3 months prior to informed consent)
-Peripheral occlusive arterial disease (previous limb bypass surgery or percutaneous transluminal angioplasty; previous limb or foot amputation due to circulatory insufficiency, angiographic or ultrasound detected significant vessel stenosis (>50%) of major limb arteries (common iliac artery, internal iliac artery, external iliac artery, femoral artery, popliteal artery), history of intermittent claudication, with an ankle: arm blood pressure ratio < 0.90 on at least one side).
B) Evidence of vascular related end-organ damage:
- Moderately impaired renal function (as defined by modified diet of renal disease (MDRD) formula) with estimated glomerular filtration rate [eGFRF]) 30-59 mL/min/1.73 m2
- Random spot urinary albumin:creatinine ratio = 30 µg/mg in two of three unrelated specimens in previous 12 months prior Visit 1a
-Proliferative retinopathy defined as retinal neovascularisation or previous retinal laser coagulation therapy.
C) Age = 70 years (at Visit 1a)
D) At least two of the following CV risk factors:
-Type 2 diabetes mellitus duration > 10 years at Visit 1a.
-Systolic blood pressure (SBP) > 140 mmHg (or on at least one blood pressure lowering treatment at Visit 1a)
-Current daily cigarette smoking
-LDL cholesterol = 135 mg/dL (3.5 mmol/l) (or specific current treatment for this lipid abnormality) at Visit 1a
3)Body Mass Index (BMI) = 45 kg/m2 at Visit 1a
4)Age = 40 and = 85 years at Visit 1a
5)Signed and dated written informed consent at the latest by the date of Visit 1a, in accordance with GCP and local legislation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
•Type 1 diabetes mellitus
•Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, GLP-1 analogue/agonists, DPP-IV inhibitors or any insulin) prior to informed consent. Note: previous short term use of insulin (up to two weeks) is allowed (e.g. during hospitalisation) if taken at least 8 weeks prior informed consent.
•Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) within 3 months prior to informed consent
•Any previous (or planned within next 12 months) bariatric surgery (open or laparascopic) or intervention (gastric sleeve)
•Current treatment with systemic steroids at time of informed consent or pre-planned initiation of such therapy
•Change in dose of thyroid hormones within 6 weeks prior informed consent
•Active liver disease or impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN)
•Pre-planned coronary artery re-vascularization (PCI, CABG) within next 6 months
•Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
•Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, has a life expectancy less than 5 years for non-CV causes, or has cancer other than non-melanoma skin cancer within last 3 years, or has any other condition than mentioned which in the opinion of the investigator, would not allow safe participation in the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method