Clinical study to evaluate the efficacy on cholesterol and blood pressure reduction and safety of Trinomia® versus usual care in patients with very high cardiovascular risk without previous cardiovascular event.
- Conditions
- Very high cardiovascular risk without previous cardiovascular eventMedDRA version: 21.1Level: PTClassification code 10064939Term: Cardiovascular event prophylaxisSystem Organ Class: 10042613 - Surgical and medical proceduresTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-004015-13-PT
- Lead Sponsor
- Ferrer Internacional, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 520
Patients must meet all the following criteria:
1) Patients of both sexes, older than 18 years.
2) Patients willing and able to sign a written informed consent form.
3) Patients with high or very high cardiovascular risk, without previous cardiovascular event (the definition of high or very high cardiovascular risk is in accordance with the european guidelines for cardiovascular prevention) and meeting at least one of the following characteristics:
3.a) Patients with subclinical atherosclerosis diagnosed by invasive or not invasive techniques (including coronary angiography, nuclear imaging, stress cardiac resonance imaging, stress echocardiography, CT scan of coronary arteries, carotid plaque by ultrasound) and taking as aortic aneurysm, atherosclerotic plaque in carotid arteries (or IMT =1,5 mm); severely calcified coronary arteries (coronary calcium> 300 U Agaston) or ABI <0.9.
3.b) Patients diagnosed with Diabetes Mellitus (I or II) or in treatment with oral hypoglycemic agents or insulin and with concomitant hypertension.
3.c) Patients diagnosed with Diabetes Mellitus (I or II) or in treatment with oral hypoglycemic agents or insulin and with concomitant albumin or protein in urine.
3.d) Patients diagnosed with hypertension (or treated with antihypertensive drugs) with one of the following concomitant clinical situations: left ventricular hypertrophy (diagnosed by electrocardiogram or ecocardiogram; left ventricular mass index > 95g/m^2 in female and > 115g/m^2 in male or interventricular septum > 11 mm),albumin or protein in urine or renal failure (GFR between 30 and 60 mL /min according to the CKD-EPI method).
4) Patients who, per investigator's opinion, have controlled LDL cholesterol and BP and kept in treatment with a stable lipid-lowering (with at least one estatine) and antihypertensive treatment (at least one ACE inhibitor or one ARB) during 3 months before randomization.
5) Patients who, per investigator's opinion, will not require a change in their lipid-lowering and/or antihypertensive medication during the 16 weeks after randomization.
6) For women with childbearing potential, there is a negative pregnancy test (urine).
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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
Patients meeting any of the folowing criteria will be rejected from the study:
1) Patient with previous clinically significant cardiovascular event (including myocardial infarction or other form of acute coronary syndrome, angina, myocardial revascularization or other vascular territory, ischemic or hemorrhagic stroke or symptomatic DBP (class II to IV by Fontaine classification).
2) Patients with contraindicated used of Trinomia®, including the following:
2.a) Patients in hemodialysis treatment or severe kidney failure (defined by glomerular filtration (calculated by using the CKD-EPI formula) <30ml/min).
2.b) Patients with ALT / AST values > 3xULN or with severe or active liver failure.
2.c) Patients hypersensitivity to any polypill component (atorvastatin, ramipril and aspirin), soybeans, peanuts, or ACE inhibitors or salicylates other than ASA or ramipril.
2.d) Patients with history of asthma attacks or nasal polyps associated with asthma, or other allergic reactions due to aspirin or other NSAIDs.
2.e) Patients with recurrent active peptic ulcer, history of gastric or intestinal bleeding, cerebrovascular bleeding or dyspepsia.
2.f) Patients with anemia or worsening in hemoglobin levels that, per investigator's assessment, make them suspect of the presence of active bleeding and thet contraindicate the use of ASA.
2.g) Patients with hemophilia or other bleeding disorders.
2.h) Patients with myopathy, myalgia, myositis or rhabdomyolysis history due to statins, or those who have a creatine kinase (CK) analysis whose result is > 5 ULN (recommended not measuring CK after intense exercise).
2.i) Patients with an angioedema or cough history due to ACE inhibitors.
2.j) Patients with bilateral kidney artery stenosis or kidney artery stenosis in a single working kidney.
3) Patients with grade III arterial hipertension (systolic blood pressure > 180 and / or diastolic blood pressure > 110mmHg).
4) Patients with suspected or diagnosed familial hypercholesterolemia.
5) Patients with triglycerides levels > 400mg/dl when patient is being included.
6) Patients diagnosed with congestive heart failure (NYHA class III-IV).
7) Patients who, per investigator's opinion, are not clinically appropriate to use Trinomia® (including atorvastatin 20 or 40 mg and ramipril 2.5 to 10 mg) as treatment for the control of LDLc and blood pressure.
8) Patients being treated with any of the following drugs: fixed dose combination of 3 antihypertensives (for patients that, at baseline, are in combination of antihypertensives which include ACEi/ASA II with calcium channel blockers, please refer to section 6.2 Ground Dose Justification), oral anticoagulants, antiplatelet agents (except ASA), chronic treatment with NSAID (occasional treatment with NSAID during the study is allowed (occasional use is considered when using ibuprofen (maximum dose of 1200mg/d) or other NSAID at an equivalent dose, for a maximum of 3 days in a one month period), CYP3A4 Inhibitors transport proteins (cyclosporine, rifampicin, telitromicine, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors such as ritonavir, lopinavir, atazanavir, indinavir, darunavir, telaprevir, etc.), other medication such as: gemfibrozil, aliskiren, methotrexate, (oral) fusidic acid, sacubitril/valsartan.
9) Patients with severe systemic disease who, per investigator's opinion, may interfere with the study procedures and assessments.
10) Patients
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