A trial to study a new therapeutic strategy (the Fuster-CNIC-Ferrer cardiovascular polypill) versus usual care on LDLc and blood pressure reduction in patients with atherothrombotic cardiovascular disease: The APOLO trial.

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; Patients with atherothrombotic cardiovascular disease; MedDRA version: 20.1Level: LLTClassification code 10007648Term: Cardiovascular disease, unspecifiedSystem Organ Class: 100000004849

• Registration Number: EUCTR2017-002343-14-IE
• Lead Sponsor: Ferrer Internacional, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-02
• Last Update Posted: 16 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 700

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

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) <30 ml/min).
1.b) Patients with moderate hepatic impairment defined as alanine aminotransferase
(ALT) or aspartate aminotransferase (AST) elevation >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 <10 g/dl) or worsening of
haemoglobin, suggesting the presence of active bleeding, according to
investigator’s criteria, which may contraindicate the use of acetylsalicylic
acid.
1.g) Patients with haemophilia or other disorders of coagulation.
1.h) Patients with myopathy, myalgia, myositis or a history of rhabdomyolysis,
or those that have creatine kinase (CK) tested and whose result is > 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified