Patients with atherothrombotic cardiovascular disease MedDRA version: 20.1 Level: LLT Classification code 10007648 Term: Cardiovascular disease, unspecified System Organ Class: 100000004849
Conditions
Sponsors
Ferrer Internacional, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age =18; both genders. 2) Subjects with atherothrombotic cardiovascular disease, with at least one of the following clinical events, the last one having occurred within the required time frame 2.a) Previous acute myocardial infarction (>6 months after the event). 2.b) Cardiac revascularization with coronary stent (>6 months after the surgery) or coronary artery bypass grafting (3 months after the surgery). 2.c) Diagnosis of stable angina (patients to be submitted to a coronary interventional procedure or functional (ischemic test) and/or anatomic (coronary stenosis assessed by coronary angiography or computed tomography). 2.d) Previous ischemic stroke with atherothrombotic background, including lacunar infarction (>6 months after the event). 2.e) Peripheral artery disease, including patients with stable claudication (>6 months) or operated patients (revascularization or amputation) (2 weeks after the surgery). 3) Subjects treated with an ACE inhibitor or ARB, statin and acetylsalicylic acid for secondary cardiovascular prevention. 4) Subjects who are clinically stable, with no changes in medication for LDLc and blood pressure control within the last 3 months, and in whom it is not planned to change their medication for LDLc and blood pressure in the following 6 months after randomisation. 5) Written informed consent form. 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 700 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 190
Exclusion criteria
Exclusion criteria: 1) Any contraindication to the polypill, such as: 1.a) Patients on haemodialysis or with severe renal impairment (defined by glomerular filtration rate (calculated by CKD-EPI formula) 3 times the upper limit of normal (ULN) or severe hepatic impairment (defined by the Child-Pugh criteria for patients with ALT/AST >5 times the ULN). 1.c) Patients with hypersensitivity to any of the components of the polypill (atorvastatin, ramipril or acetylsalicylic acid), soy, peanuts, or to any ACE inhibitors or salicylates other than acetylsalicylic acid or ramipril. 1.d) Patients with a history of asthma episodes or nasal polyps associated with asthma, or other allergic reactions due to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. 1.e) Patients with active recurrent peptic ulcer, history and/or active gastric or intestinal bleeding, cerebrovascular haemorrhage, or regular history of dyspepsia. 1.f) Patients with anaemia (haemoglobin 5 LSN (it is recommended not to measure CK after intense exercise). 1.i) Patients with a history of angioedema or cough due to ACE inhibitors. 1.j) Patients with bilateral renal artery stenosis or renal artery stenosis with a single functioning kidney. 2) Patients in whom, at the discretion of the investigator, it is not clinically appropriate to use the polypill (including atorvastatin 20 or 40 mg and ramipril 2.5 to 10 mg) as treatment for the control of LDLc cholesterol and blood pressure. 3) Subjects with suspected familiar hypercholesterolemia or triglycerides >400 mg/dl. 4) Patients with hypotensive or haemodynamically unstable states. 5) Subjects with diagnosed of congestive heart failure (New York Heart Association [NYHA] class III-IV). 6) Patients diagnosed with atrial fibrillation. 7) Patients with haemorrhagic stroke, cardioembolic stroke or stroke of undetermined aetiology. 8) Patients taking any of the following medication: - Treatment with a fixed dose combination of 3 antihypertensives. - Chronic treatment with non-steroidal anti-inflammatory drugs; its occasional use is allowed. It will be considered occasional use when ibuprofen (maximal dose 1200 mg/day), or other non-steroidal anti-inflammatory drugs at equivalent dose, is used for a maximum of 3 days in a period of one month. - Potent inhibitor of CYP3A4 or transport proteins (e.g. ciclosporin, rifampicin, telitromicin, claritromicin, delavirdin, estiripentol, ketoconazol, voriconazol, itraconazol, posaconazol and HIV protease inhibitors such as ritonavir, lopinavir, atazanavir, indinavir, darunavir, telaprevir, etc). - Other medications as: Gemfibrozil, Aliskiren, Methotrexate, Fusidic acid (oral) or Sacubitril /Valsartan 9) Women who are pregnant, breastfeeding or planning to become pregnant during the study, as well as fertile women who do not take adequate contraceptive measures such as: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovula
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to determine whether the treatment with a new therapeutic strategy (Trinomia®)) is at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDLc) and systolic blood pressure reductions in subjects with atherothrombotic cardiovascular disease after 6 months of treatment.;Secondary Objective: Blood pressure and LDLc levels at the end of the treatment period in subgroups of patients with atherothrombotic cardiovascular disease with coronary artery disease, stroke and/or peripheral artery disease. ? Changes in the SBP / DBP and LDL-c levels from baseline to month 6. Total cholesterol, HDLc, non-HDLc and triglyceride levels at the end of the treatment period Changes in total cholesterol, HDLc, non-HDLc and triglyceride levels from baseline to month 6. Patients’ satisfaction with medication according to the abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9; Appendix 2) and patients’ preferences reported in the specific ad-hoc questions on treatment preferences (Appendix 3) at the end of the treatment period.;Primary end point(s): systolic blood pressure and LDLc values;Timepoint(s) of evaluation of this end point: At the end of the study treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Blood pressure and LDLc levels at the end of the treatment period in subgroups of patients with atherothrombotic cardiovascular disease with coronary artery disease, stroke and/or peripheral artery disease. Changes in the SBP / DBP and LDL-c levels from baseline to month 6. The percentage of patients with LDLc and blood pressure under control as per the 2016 European Guidelines on Cardiovascular Disease Prevention at month 63; the LDLc and blood pressure control as per these guidelines is defined as: LDLc levels: - In patients at very high cardiovascular risk (including patients in secondary prevention), an LDLc goal 60 years with systolic blood pressure =160 mmHg, target between 150 and 140 mmHg. - In fit patients aged 80 years and with initial systolic blood pressure =160 mmHg, systolic blood pressure between 140 and 150 mmHg. - In diabetic patients: systolic blood pressure <140mmHg and diastolic blood pressure <85mmHg Total cholesterol, HDLc, non-HDLc and triglyceride levels at the end of the treatment period Changes in total cholesterol, HDLc, non-HDLc and triglyceride levels from baseline to month 6. Patients’ satisfaction with medication according to the abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9; Appendix 2) and patients’ preferences reported in the specific ad-hoc questions on treatment preferences (Appendix 3) at the end of the treatment period. The safety of the polypill will be assessed according to the occurrence of adverse events (AEs; e.g. cardiovascular events, other AEs, serious AEs [SAEs] and AEs causing withdrawal) throughout the study.;Timepoint(s) of evaluation of this end point: At month 6 and throughout the study. | — |
Countries
Ireland, Italy, Mexico, Portugal, Spain, Ukraine
Contacts
Public ContactDirector
Clinical Trial EndPoint Ltd.
Outcome results
None listed