CAROLINA: Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients With Type 2 Diabetes
- 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: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2009-013157-15-PT
- Lead Sponsor
- nilfarma - União Internacional de Lab. Farmacêuticos, Lda.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 10606
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 (if intolerant or contra-indicated to first line anti-diabetic treatment) 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 + SU (combination maximal up to 5 years), or
- metformin + glinide (combination maximal up to 5 years) or
- alpha-glucosidase inhibitor + SU (combination maximal up to 5 years),
- alpha-glucosidase inhibitor + 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 or disease (=50% luminal diameter narrowing of left main coronary artery or =50% 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, stenting 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 (= 3.4 mg/mmol) 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
• Type 1 diabetes mellitus
• Any history and/or current treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, GLP-1 analogue/agonists, DPP-IV inhibitors or any insulin) prior to informed consent. Note 1: This also includes clinical trials where these antidiabetic drugs have been provided to the patient. Note 2: previous short term use of any insulin (up to two consecutive 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
Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3
mmol/L) after an overnight fast during placebo run-in and confirmed by
a second measurement (not on the same day)
• Any previous (or planned within next 12 months) bariatric surgery (open or laparascopic) or intervention (gastric sleeve)
• Current treatment with systemic corticosteroids at time of informed consent or pre-planned initiation of such therapy Note: inhaled use of steroids (e.g. for asthma/COPD) is no exclusion criterion, as this does not cause systemic steroid action
• 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) as determined at visit 1a
• Pre-planned coronary artery re-vascularization (PCI, CABG) within next 6 months after V1a or any previous PCI and/or CABG = 6 weeks prior informed consent
• Known hypersensitivity or allergy to the investigational product or its excipients, or glimepiride (or the SU class).
Known hypersensitivity or allergy to the investigational product or its
excipients, or glimepiride (or the SU class)
• Inappropriateness of glimepiride treatment for renal safety issues or other issues (e.g. allergy) according to local prescribing information
Pre-menopausal women (last menstruation = 1 year prior to informed
consent) who are nursing or pregnant,or are of child-bearing potential
and are not practicing an acceptable method of birth control (acceptable methods of birth control include tubal ligation, transdermal patch, intrauterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local authorities), double barrier method and vasectomised partner) or do not plan to continue using acceptable method of birth control throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
Congestive heart failure of NYHA class III or IV
• Acute or chronic metabolic acidosis (present condition in patient history)
• Hereditary galactose intolerance
• Alcohol or drug abuse within the 3 months prior to informed consent
that would interfere with trial participation
• Participation in another trial with an investigational drug given within 2 months prior to informed consent
•Patients considered unreliable by the investigat
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