SECURE: Secondary Prevention of Cardiovascular Disease in the Elderly Trial

Sponsor

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (Other)

Overall Status

Completed

CT.gov ID

NCT02596126

Collaborator

Charite University, Berlin, Germany (Other), Centre Hospitalier Universitaire de Besancon (Other), Wroclaw Medical University (Other), Semmelweis University (Other), General University Hospital, Prague (Other), Servicio Madrileño de Salud, Madrid, Spain (Other), London School of Hygiene and Tropical Medicine (Other), Ferrer Internacional S.A. (Industry), Istituto Di Ricerche Farmacologiche Mario Negri (Other)

2,499

Enrollment

113

Locations

Arms

Duration (Months)

22.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of a polypill strategy containing aspirin (100 mg), ramipril (2.5, 5 or 10 mgs), and atorvastatin (40 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) in elderly patients with a recent myocardial infarction.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction Cardiovascular Disease	Drug: Cardiovascular Polypill Drug: Treatment Prevention for Secondary CV	Phase 3

Detailed Description

A total number of 3206 patients will be randomized (1:1) to treatment arms. Patients will be recruited across seven countries in Europe (Spain, Italy, Germany, France, Hungary, Poland, and Czech Republic).

Patients will be ≥65 years old and diagnosed with a type 1 myocardial infarction within 6 months prior to study enrolment.

Once the inclusion and exclusion criteria are confirmed, patients will be included in the study after signing informed consent.

Randomization will take place within 6 months of the index event (AMI type I) in a 1:1 ratio to one of the two arms:

Cardiovascular Polypill (containing Aspirin, Ramipril, and Atorvastatin)
Usual care

Patients will be followed up for a minimum of 2 years and a maximum of 4 years.

There will be 3 follow up visits at month 6, 12 and 24 and telephone follow up calls at month 18, 36 and 48

Study Design

Study Type:

Interventional

Actual Enrollment :

2499 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Secondary Prevention of Cardiovascular Disease in the Elderly Trial

Study Start Date :

Jul 1, 2016

Actual Primary Completion Date :

Oct 31, 2021

Actual Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Prevention for Secondary CV Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the ESC guidelines. Drugs and doses will be left at the discretion of the treating physicians..	Drug: Treatment Prevention for Secondary CV ESC Guideline (2013 guideline on management of stable coronary disease) recommended pharmacological treatment for event prevention. Other Names: Antiplatelet agents Lipid Lowering Agents Renin-angiotensin-aldosterone system blockers
Experimental: Cardiovascular Polypill Patients allocated to the experimental arm will receive a cardiovascular polypill containing aspirin 100 mg, atorvastatin (40 or 20 mg) and ramipril (2.5, 5 or 10 mg) taken orally once a day.	Drug: Cardiovascular Polypill Cardiovascular Polypill contains Aspirin, Atorvastatin and Ramipril. Participants will receive one of the following cardiovascular polypill: (A) Aspirin 100 mg, Atorvastatin 40mg, and Ramipril (2.5 mg, or 5 mg, or 10mg). or (B) Aspirin 100 mg, Atorvastatin 20mg, and Ramipril (2.5 mg, or 5 mg, or 10mg). Other Names: Polypill

Arm

Intervention/Treatment

Active Comparator: Treatment Prevention for Secondary CV

Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the ESC guidelines. Drugs and doses will be left at the discretion of the treating physicians..

Drug: Treatment Prevention for Secondary CV

ESC Guideline (2013 guideline on management of stable coronary disease) recommended pharmacological treatment for event prevention.

Other Names:

Antiplatelet agents

Lipid Lowering Agents

Renin-angiotensin-aldosterone system blockers

Experimental: Cardiovascular Polypill

Patients allocated to the experimental arm will receive a cardiovascular polypill containing aspirin 100 mg, atorvastatin (40 or 20 mg) and ramipril (2.5, 5 or 10 mg) taken orally once a day.

Drug: Cardiovascular Polypill

Cardiovascular Polypill contains Aspirin, Atorvastatin and Ramipril. Participants will receive one of the following cardiovascular polypill: (A) Aspirin 100 mg, Atorvastatin 40mg, and Ramipril (2.5 mg, or 5 mg, or 10mg). or (B) Aspirin 100 mg, Atorvastatin 20mg, and Ramipril (2.5 mg, or 5 mg, or 10mg).

Other Names:

Polypill

Outcome Measures

Primary Outcome Measures

Difference in the occurrence of Major Adverse Cardiovascular Events (MACE) between the Cardiovascular Combination Polypill AAR and the Standard of Care Treatment [24 months]
Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization

Secondary Outcome Measures

Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI, stroke. [Baseline]
Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization
Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI, stroke. [6 months after treatment initiation]
Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization
Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI, stroke. [12 months after treatment initiation]
Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization
Evaluate the first occurrence of the individual components of the primary endpoint [18 months after treatment initiation]
CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization.
Evaluate the first occurrence of the individual components of the primary endpoint [24 months after treatment initiation]
CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization.
Evaluate the first occurrence of the individual components of the primary endpoint [36 months after treatment initiation]
CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization.
Evaluate the first occurrence of the individual components of the primary endpoint [48 months after treatment initiation]
CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization.
Change in Treatment Adherence [6 months after patient treatment]
The Morisky-Medication Adherence Scale (8 item) Questionnaire will be administered
Change in Treatment Adherence [24 months after patient treatment]
The Morisky-Medication Adherence Scale (8 item) Questionnaire will be administered
Change in Patient Satisfaction [6 months after patient treatment]
The treatment Satisfaction Questionnaire for Medication (TSQM) will be administered
Change in Patient Satisfaction [24 months after patient treatment]
The treatment Satisfaction Questionnaire for Medication (TSQM) will be administered
Change in Systolic and Diastolic Blood Pressure (SBP and DBP) [Baseline]
Systolic and diastolic blood pressure will be collected and summarized at each timepoint.
Change in Systolic and Diastolic Blood Pressure (SBP and DBP) [6 months after patient treatment]
Systolic and diastolic blood pressure will be collected and summarized at each timepoint.
Change in Systolic and Diastolic Blood Pressure (SBP and DBP) [12 months after patient treatment]
Systolic and diastolic blood pressure will be collected and summarized at each timepoint.
Change in Systolic and Diastolic Blood Pressure (SBP and DBP) [24 months after patient treatment]
Systolic and diastolic blood pressure will be collected and summarized at each timepoint.
Change in LDL cholesterol level [Baseline]
Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint.
Change in LDL cholesterol level [12 months after patient treatment]
Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint.
Change in LDL cholesterol level [24 months after patient treatment]
Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint.
Regional differences in performance of the polypill in the previous endpoints [6 months after patient treatment]
Assessed
Regional differences in performance of the polypill in the previous endpoints [12 months after patient treatment]
Assessed
Regional differences in performance of the polypill in the previous endpoints [24 months after patient treatment]
Assessed
Health Economic Evaluation Comparing Intervention and Usual Care Arm [6 months after patient treatment]
Cost differences and Incremental Cost-Effectiveness Ratio (ICER) will be assessed at each timepoint.
Health Economic Evaluation Comparing Intervention and Usual Care Arm [12 months after patient treatment]
Cost differences and Incremental Cost-Effectiveness Ratio (ICER) will be assessed at each timepoint.
Health Economic Evaluation Comparing Intervention and Usual Care Arm [24 months after patient treatment]
Cost differences and Incremental Cost-Effectiveness Ratio (ICER) will be assessed at each timepoint.
Change in Quality of Life [Baseline]
The European Quality of Life- 5 Dimensions (EQ-5D) Questionnaire will be administered at each timepoint to evaluate change in quality of life.
Change in Quality of Life [24 months after patient treatment]
The European Quality of Life- 5 Dimensions (EQ-5D) Questionnaire will be administered at each timepoint to evaluate change in quality of life.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Baseline]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [6 months after patient treatment]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [12 months after patient treatment]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [18 months after patient treatment]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [24 months after patient treatment]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [36 months after patient treatment]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [48 months after patient treatment]
All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation).

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients diagnosed with a type 1 myocardial infarction within the previous 6 months.
Subjects must be ≥65 years old, presenting with at least one of the following additional conditions:

Documented diabetes mellitus or previous treatment with oral hypoglycemic drugs or insulin.
Mild to moderate renal dysfunction: creatinine clearance 60-30 mL/min/1.73 m2.
Prior myocardial infarction: defined as an AMI occurring before the index event documented in a medical report.
Prior coronary revascularization: coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).
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.
Age ≥ 75 years.

Signing informed consent.

Exclusion Criteria:

Unable to sign informed consent.
Contraindications to any of the components of the polypill.
Living in a nursing home.
Mental illness limiting the capacity of self-care.
Participating in another clinical trial.
Severe congestive heart failure (NYHA III-IV).
Severe renal disease (Creatinine Clearance (CrCl) <30ml/min/1.73 m2).
Need for oral anticoagulation at the time of randomization or planned in the future months.
Any condition limiting life expectancy <2 years, including but not limited to active malignancy.
Significant arrhythmias (including unresolved ventricular arrhythmias or atrial fibrillation).
Scheduled coronary revascularization (patients can be randomized after final revascularization is completed within the prespecified timeframe).
Do not agree to the filing, forwarding and use of his/ her pseudonymised data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fakultní nemocnice Královské Vinohrady	Praha	Praha 10	Czechia	10034
2	Nemocnice Na Homolce	Praha	Praha 5	Czechia	15030
3	Všeobecná fakultní nemocnice v Praze	Praha 2	Praha	Czechia	12808
4	Nemocnice Rudolfa a Stefanie Benešov	Benešov		Czechia	25601
5	Nemocnice Jihlava	Jihlava		Czechia	58633
6	Krajská necmonice Liberec	Liberec		Czechia	46030
7	Fakultní nemocnice Olomouc	Olomouc		Czechia	77900
8	Nemocnice Slaný	Slaný		Czechia	27401
9	Nemocnice Podlesí	Třinec		Czechia	73961
10	Centre Hospitalier Universitaire d'Angers	Angers		France	49933
11	Centre Hospitalier Régional Universitaire de Besançon	Besançon		France	25030
12	Centre Hospitalier Universitaire de Lyon	Bron		France	69500
13	Centre Hospitalier Universitaire de Caen	Caen		France	14000
14	Centre Hospitalier Metropole Savoie	Chambéry		France	73000
15	Centre Hospitalier Universitaire Henri Mondor	Créteil		France	94000
16	Centre Hospitalier Universitaire de Dijon	Dijon		France	21000
17	Centre Hospitalier Universitaire de Grenoble	Grenoble		France	38000
18	Centre Hospitalier Régional et Universitaire de Lille	Lille		France	59037
19	Centre Hospitalier St Joseph St Luc	Lyon		France	69365
20	Centre Hospitalier Universitaire de Nice	Nice		France	06002
21	Hôpital Bichât	Paris		France	75010
22	Centre hospitalier Universitaire de Bordeaux	Pessac		France	33604
23	Centre Hospitalier Universitaire de Toulouse	Toulouse		France	31403
24	Medical Park Berlin Humboldtmühle	Berlin - Tegel	Berlin	Germany	13507
25	Immanuel Klinikum Bernau Herzzentrum Brandenburg	Bernau	Berlin	Germany	16321
26	Brandenburgklinik Berlin-Brandenburg GmbH, Haus Brandenburg/ Kardiologie	Waldsiedlung	Berlin	Germany	16321
27	Klinik am See, Rehabilitationszentrum für innere Medizin	Rüdersdorf	Brandenburg	Germany	15562
28	GLG Fachklinik Wolletzsee GmbH	Angermünde		Germany	16278
29	AVK Vivantes Rehabilitation GmbH	Berlin		Germany	12157
30	DRK- Kliniken Berlin/ Köpenick	Berlin		Germany	12559
31	Maria Heimsuchung Caritas-Klinik Pankow	Berlin		Germany	13187
32	Jüdisches Krankenhaus	Berlin		Germany	13347
33	Charité - Universitätsmedizin Berlin, Centrum für Schlaganfallforschung (CSB)	Berlin		Germany	13353
34	Vivantes Humboldt Klinikum	Berlin		Germany	13509
35	Vivantes Klinikum Spandu	Berlin		Germany	13585
36	DRK Klinik Berlin Westend	Berlin		Germany	14050
37	GK Havelhöhe	Berlin		Germany	14089
38	Gesundheitszentrum Bitterfeld /Wolfen GmbH	Bitterfeld-Wolfen		Germany	06749
39	Mediclin Reha-Zentrum Spreewald Fachklinik für innere Medizin	Burg		Germany	03096
40	MediClin Herzzentrum Coswig	Coswig		Germany	06869
41	Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika	Budapest		Hungary	1122
42	Fővárosi Szent János Kórház	Budapest		Hungary	1125
43	Szent Rókus Kórház és Intézményei	Budapest		Hungary	H-1085
44	Békés Megyei Pándy Kálmán Kórház	Gyula		Hungary	5700
45	Bács- Kiskun Megyei Kórház	Kecskemét		Hungary	6000
46	Fejér Megyei Szent György Egyetemi Kórház	Székesfehérvár		Hungary	8000
47	Sydó és Tsa Kft.	Veszprém		Hungary	H-8200
48	IRCCS Fondazione S. Maugeri Istit. di Cassano Murge	Cassano Delle Murge	BA	Italy	70020
49	IOB-Policlinico San Marco	Osio Sotto	BG	Italy	24040
50	Ospedale Bolognini di Seriate - ASST BERGAMO EST	Seriate	BG	Italy	24068
51	ASST di Bergamo Ovest-Ospedale di Treviglio	Treviglio	BG	Italy	24047
52	ASST Degli Spedali Civili di Brescia	Brescia	BS	Italy	25123
53	Ospedale S.Lazzaro	Alba	CN	Italy	12051
54	Ospedale Generale di Zona-Ospedale Valduce	Como	CO	Italy	22100
55	ASL FG Ospedale "Teresa Masselli Mascia"	San Severo	FG	Italy	71016
56	Ospedale Misericordia ASL 9 Grosseto	Grosseto	GR	Italy	58100
57	Ospedale Sacro Cuore di Gesù	Gallipoli	LE	Italy	73014
58	ASST Di Monza-Presidio Ospedaliero di Desio	Desio	MB	Italy	20832
59	ASST Di Monza-Ospedale San Gerardo	Monza	MB	Italy	20900
60	IRCCS Ospedale Policlinico di Milano	Milano	MI	Italy	20122
61	Centro Cardiologico Monzino SpA	Milano	MI	Italy	20138
62	ASST Santi Paolo e Carlo-Ospedale San Paolo-Polo Univ.	Milano	MI	Italy	20142
63	IRCCS-Fondazione Don Carlo Gnocchi	Milano	MI	Italy	20149
64	IRCCS Istituto Clinico Humanitas	Rozzano	MI	Italy	20089
65	IRCCS Policlinico San Donato	San Donato Milanese	MI	Italy	20097
66	Ospedale di Sassuolo S.P.A.	Sassuolo	MO	Italy	41049
67	ASST Rhodense Ospedale di Passirana	Passirana	Passirana-rho	Italy	20017
68	Presidio Ospedaliero San Filippo Neri-ASL Roma E	Roma	RM	Italy	00135
69	A.O. San Camillo Forlanini	Roma	RO	Italy	00149
70	Ospedale Ss Giovanni di Dio e Ruggi d'Aragona	Salerno	SA	Italy	84131
71	Casa di Cura Villa Bianca	Trento	TN	Italy	38122
72	AAS3 "Alto Friuli, Collinare, Medio Friuli" Ospedale di San Daniele del Friuli-Tolmezzo sede di S. D. del Friuli	San Daniele Del Friuli	UD	Italy	33038
73	ASST Della Valle Olona-Ospedale di Saronno	Saronno	VA	Italy	21047
74	Samodzielny Publiczny Szpital Kliniczny nr 7, Śląskiego Uniwersytetu Medycznego w Katowicach, Górnośląskie Centrum Medyczne im. prof. Leszka Gieca	Katowice	Ochojec	Poland	40-635
75	Uniwersyteckie Centrum Kliniczn	Gdańsk		Poland	80-952
76	Szpital Wielospecjalistyczny im. Dr. Ludwika Błażka w Inowrocławiu	Inowrocław		Poland	88-100
77	Krakowski Szpital Specjalistyczny im. Jana Pawła II	Kraków		Poland	31-202
78	Zespół Opieki Zdrowotnej w Kłodzku	Kłodzko		Poland	57-300
79	Wojewódzki Szpital Specjalistyczny w Legnicy	Legnica		Poland	59-220
80	Specjalistyczny Szpital im. Dra Alfreda Sokołowskiego	Wałbrzych		Poland	58-309
81	Centrum Kardiologiczne "Pro Corde" Sp. z o.o.	Wrocław		Poland	50-315
82	Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ	Wrocław		Poland	50-981
83	Samodzielny Publiczny Zespół Opieki Zdrowotnej w Świdnicy	Świdnica		Poland	58-100
84	Hospital Universitario de Cabueñes	Gijón	Asturias	Spain	33203
85	Hospital Univeristari de Bellvitge	L'Hospitalet De Llobregat	Barcelona	Spain	08997
86	H.C.U.de Santiago De Compostela	Santiago De Compostela	Galicia	Spain	15706
87	Complejo Asistencial Universitario de Leon	León	Leon	Spain	24008
88	Hospital Universitario Principe de Asturias	Alcalá De Henares	Madrid	Spain	28805
89	Hospital General de Villalba	Collado-Villalba	Madrid	Spain	28400
90	Hospital de Fuenlabrada	Fuenlabrada	Madrid	Spain	28492
91	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
92	Hospital Universitario Rey Juan Carlos	Móstoles	Madrid	Spain	28933
93	Hospital Universitario QuironSalud Madrid	Pozuelo De Alarcón	Madrid	Spain	28223
94	Hospital Universitario Infanta Elena	Valdemoro	Madrid	Spain	28340
95	H.C.U. Virgen De La Arrixaca De Murcia	El Palmar	Murcia	Spain	30120
96	Hospital Universitario A Coruña	A Coruña		Spain	15006
97	Hospital General Universitario de Alicante	Alicante		Spain	03010
98	Hospital Universitari Vall D'hebron	Barcelona		Spain	08035
99	Hospital Clinic de Barcelona	Barcelona		Spain	08036
100	Hospital Universitario Reina Sofia de Cordoba	Córdoba		Spain	14004
101	Hospital La Luz Quiron	Madrid		Spain	28003
102	C.H.U. Ruber Juan Bravo	Madrid		Spain	28006
103	Hospital Universitario La Princesa	Madrid		Spain	28006
104	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28009
105	Hospital Universitario Clinico San Carlos	Madrid		Spain	28040
106	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
107	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
108	Hospital Virgen de la Victoria	Málaga		Spain	29010
109	Complejo Asistencial Universitario de Salamanca	Salamanca		Spain	37007
110	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
111	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
112	Hospital Clinic Universitari de Valencia	Valencia		Spain	46010
113	Hospital Universitario y Politécnico de La Fe	Valencia		Spain	46026

Sponsors and Collaborators

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Charite University, Berlin, Germany
Centre Hospitalier Universitaire de Besancon
Wroclaw Medical University
Semmelweis University
General University Hospital, Prague
Servicio Madrileño de Salud, Madrid, Spain
London School of Hygiene and Tropical Medicine
Ferrer Internacional S.A.
Istituto Di Ricerche Farmacologiche Mario Negri

Investigators

Principal Investigator: Valentin Fuster, MD, PhD, Centro Nacional de Investigaciones Cardiovasculares Carlos III
Study Director: Jose Maria Castellano Vazquez, MD, PhD, Centro Nacional de Investigaciones Cardiovasculares Carlos III