| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Secondary Prevention of Major Cardiovascular Events (cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent revascularization) in post MI cohort. |
| Prevenzione secondaria dell'infarto del miocardio |
|
| E.1.1.1 | Medical condition in easily understood language |
| Secondary Prevention of Major Cardiovascular Events (cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent revascularization) |
| Prevenzione secondaria dell'infarto del miocardio |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028597 |
| E.1.2 | Term | Myocardial infarction acute |
| E.1.2 | System Organ Class | 100000004849 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy of a polypill strategy containing aspirin (100 mg), ramipril (2.5, 5 or 10 mgs), and atorvastatin (40 or 20 mgs) compared with the standard of care (usual care according to the local clinical practices at each participating country) in secondary prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent revascularization).
|
| Valutare l¿efficacia della strategia polipillola, contenente aspirina (100mg), atorvastatina (40 o 20 mg), ramipril (2.5, 5 o 10 mg) rispetto alla terapia standard nella prevenzione secondaria degli eventi cardiovascolari maggiori (morte per cause cardiovascolari, infarto miocardico e ictus ischemico non fatali, rivascolarizzazione d¿urgenza) nei pazienti anziani (et¿ = 65 anni) con infarto del miocardio |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate a polypill strategy as compared with standard of care for secondary cardiovascular prevention after MI in an elderly population in:
- reducing other clinical endpoints.
- improving baseline adherence.
- improving quality of life.
- controlling cardiovascular risk factors. (LDL cholesterol, systolic and diastolic blood pressure).
- Cost-effectiveness
- safety and tolerability
- patient satisfaction
- performance across the different socioeconomic and health settings.
|
Valutare se la strategia polipillola, rispetto alla terapia standard:
riduce la mortalit¿ e gli altri endpoint clinici; migliora l'aderenza; migliora la qualit¿ di vita; ¿ efficace nel controllo dei fattori di rischio cardiovascolare (profilo lipidico e pressione arteriosa).
Valutare:
il costo/efficacia; la sicurezza e la tollerabilit¿; la preferenza del paziente. Valutare la ¿strategia polipillola¿ tra i diversi contesti culturali e i differenti sistemi sanitari. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients diagnosed with a type 1 myocardial infarction within the previous 8 weeks.
2. Subjects must be =65 years old, presenting with at least one of the following additional conditions:
I. Documented diabetes mellitus or previous treatment with oral hypoglycemic drugs or insulin.
ii. Mild to moderate renal dysfunction: creatinine clearance 60-30 mL/min/1.73 m2.
iii. Prior myocardial infarction: defined as an AMI occurring before the index event documented in a medical report.
iv. Prior coronary revascularization: coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).
v. Prior stroke: history of a documented stroke, defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of central nervous system tissue, not resulting in death.
vi. Age = 75 years.
3. Signing informed consent. |
1. Pazienti che acconsentono di partecipare allo studio dopo essere stati adeguatamente informati.
2. Pazienti con infarto miocardico acuto- tipo I (entro 8 settimane dall’evento).
3. I soggetti devono avere un’età =65 anni e presentare almeno uno delle seguenti condizioni:
- diabete mellito, o trattamento con ipoglicemizzanti orali o insulina;
- insufficienza renale da lieve a moderata (60-30 ml/min/1.73 m2);
- pregresso infarto miocardico;
- pregresso intervento di rivascolarizzazione coronarica (bypass aorto-coronarico, angioplastica coronarica);
- pregresso ictus cerebrale;
- età =di 75 anni; |
|
| E.4 | Principal exclusion criteria |
1. Unable to sign informed consent.
2. Contraindications to any of the components of the polypill.
3. Living in a nursing home or committed to an institution by virtue of and order issued by the judicial or the administrative authorities.
4. Mental illness limiting the capacity of self-care.
5. Participating in another clinical trial.
6. Severe congestive heart failure (NYHA III-IV).
7. Severe renal disease (Creatinine Clearance (CrCl) <30ml/min/1.73 m2).
8. Severe hepatic impairment. Liver cirrhosis transaminases exceeding 3 times the upper limit of the normal limit.
9. Allergies to lactose, peanut, or soy.
10. Need for oral anticoagulation at the time of randomization or planned in the future months.
11. Any condition limiting life expectancy <2 years, including but not limited to active malignancy.
12. Significant arrhythmias (including unresolved ventricular arrhythmias or atrial fibrillation).
13. Scheduled coronary revascularization (patients can be randomized after final revascularization is completed within the pre-specified timeframe).
14. Do not agree to the filing, forwarding and use of his/ her pseudonymised data.
15. Individuals dependent from the sponsor, investigator or investigational site / institution. |
1. Pazienti non in grado di firmare il consenso informato
2. Controindicazioni a uno dei componenti della polipillola.
3. Ricovero in casa di cura o internato in una istituzione su mandato di autorità giudiziarie o amministrative.
4. Disturbi mentali che compromettono la capacità di essere autosufficienti.
5. Partecipazione ad un altro trial.
6. Insufficienza cardiaca congestizia (NYHA III-IV).
7. Insufficienza renale grave (clearence della creatinina <30 ml/min/1.73m2).
8. Insufficienza epatica grave. Cirrosi. Livello di transaminasi che eccede di tre volte il limite superiore di normalità.
9. Allergia nota al lattosio, nocciole o soya.
10. Uso di anticoagulanti orali al momento della randomizzazione o programmato per i mesi successivi.
11. Aspettativa di vita < a 2 anni.
12. Aritmie rilevanti (incluse aritmie ventricolari persistenti o fibrillazione atriale).
13. Pazienti che devono essere sottoposti a rivascolarizzazione (i pazienti potranno essere randomizzati se questa verrà effettuata entro le 8 settimane stabilite dal protocollo).
14. Che negano il consenso all’utilizzo dei propri dati.
15. Soggetti che dipendono dallo sponsor, dal ricercatore o dall’istituzione a cui appartiene il ricercatore.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The incidence of the first occurrence of any component of the following composite endpoint, as adjudicated by the Clinical Events Committee: • Cardiovascular death. • Any nonfatal type 1 myocardial infarction. • Any nonfatal ischemic stroke. • Any urgent coronary revascularization not resulting in death. |
L’incidenza del primo tra i seguenti eventi che compongono l’end point combinato aggiudicati dal Clinical Events Committee
• Morte cardiovascolare
• Infarto miocardico (tipo 1) non fatale
• Ictus ischemico non fatale
• Rivascolarizzazione coronarica d’urgenza
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Evaluated throughout the entire duration of study |
| Valutato per tutta la durata dello studio |
|
| E.5.2 | Secondary end point(s) |
1. Efficacy endpoints
a. Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI type 1, stroke.
b. The first occurrence of the individual components of the primary endpoint
¿ CV death.
¿ Nonfatal type 1 myocardial infarction.
¿ Nonfatal ischemic stroke.
¿ Urgent coronary revascularization.
c. Treatment adherence
d. Patient Satisfaction
e. Change of Risk Factor at Two Years: (SBP and DBP and LDL cholesterol level)
f. Regional differences in performance of the polypill strategy across different socioeconomic and health settings
2. Health Economic Endpoints.
a. Quality of life
b. Cost differences and incremental Cost-Effectiveness Ratio (ICER)
3. Safety endpoints
a. All-cause mortality: Any death not covered by the above definitions, such as that cost by infection, malignancy, sepsis, pulmonary causes, accident, suicide, or trauma
b. Adverse Events
i. Bleeding: according to Bleeding Academic Research Consortium Definition 19.
ii. Renal dysfunction (increase in creatinine by 0.5 mg/dl or more) or hyperkalemia (K5.5 mEq/L) reported by physician in charge and leading to a change in doses or drug interruption.
iii. Drug allergies.
iv. Refractory cough leading to drug discontinuation.
c. Drug Discontinuation.
|
1. Di efficacia
a. Il primo evento che accade, tra quelli che compongono il seguente endpoint combinato: morte cardiovascolare, infarto miocardico (tipo 1), ictus ischemico.
b. Il primo evento che accade, come componente individuale dell¿ endpoint primario:
¿ Morte cardiovascolare;
¿ Infarto miocardico (tipo 1);
¿ Ictus ischemico;
¿ Rivascolarizzazione coronarica urgente.
c. Miglioramento dell¿aderenza al trattamento dopo 2 anni misurata con la scala Morisky Medication Adherence.
d. Cambiamento nel controllo dei fattori di rischio a 2 anni (LDL, pressione sistolica e diastolica).
e. Costo efficacia della strategia polipillola.
f. Valutare la ¿strategia polipillola¿ tra i diversi contesti culturali e i differenti sistemi sanitari.
g. Soddisfazione dei pazienti.
h. Qualit¿ della vita
i. Rapporto Costo Efficacia (ICER)
2. Sicurezza
a. Mortalit¿ per qualsiasi causa
b. Eventi avversi
i. Sanguinamento
ii. Disfunzione renale
iii. Reazioni allergiche al farmaco
iv. Tosse persistente comporta l¿interruzione del trattamento.
c. Interruzione del trattamento.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Efficay: Entire duration of study
2. Safety Endpoibnts: Entire duration of study
3. Health Econimic: Baseline and 24 months |
1. Efficacia (per tutta la durata dello studio)
2. Sicurezza (per tutta la durata dello studio).
3. Costo efficacia al basale e a 24 mesi |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Terapia standard per la prevenzione cardiovascolare secondaria, in accordo con la pratica clinica pr |
| Usual care for secondary prevention of cardiovascular disease, according to the local clinical pract |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 19 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 87 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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