TREatment With Beta-blockers After myOcardial Infarction withOut Reduced Ejection fracTion"

TREatment With Beta-blockers After myOcardial Infarction withOut Reduced Ejection fracTion

REBOOT clinical trial will study whether long-term maintenance beta-blockers therapy results in a clinical benefit after heart attack without reduced left ventricular function. Half of the participants will be randomized to receive long-term beta-blocker therapy and the other half to no beta-blocker therapy after hospital discharge. All patients will be followed up for up to 5 years to determine the occurrence of adverse events (all cause mortality, re-infarction, and heart failure admission).

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Beta blocker

Detailed Description

Pragmatic, controlled, prospective, randomized, open-label, blinded endpoint clinical trial testing the benefits of beta-blocker maintenance therapy in patients discharged after an acute myocardial infarction (MI). Patients being discharged after an acute MI, with or without ST-segment elevation, and with a left ventricular ejection fraction >40%, and without history of heart failure (HF) prior to study inclusion, will be recruited. At discharge, patients will be randomized (1:1) to receive beta-blocker therapy (agent and dose according to treating physician) or no beta-blocker therapy. Primary outcome is the 5 years incidence of MACE (all cause mortality, reinfarction, heart failure admission).

• Study Type: Interventional
• Enrollment (Actual): 8505
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy
    • Ospedale Civile Santi Antonio e Biagio
  • Ancona, Italy
    • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Baggiovara, Italy
    • Ospedale Civile
  • Bari, Italy
    • Ospedale San Paolo
  • Bari, Italy
    • Istituto Maugeri IRCCS
  • Bologna, Italy
    • Ospedale Maggiore
  • Caserta, Italy
    • A.O. Sant'Anna e San Sebastiano di Caserta
  • Cortona, Italy
    • Santa Margherita
  • Cremona, Italy
    • Ospedale di Cremona
  • Desio, Italy
    • Ospedale di Desio
  • Empoli, Italy
    • Ospedale San Giuseppe
  • Fidenza, Italy
    • Ospedale di Vaio
  • Foggia, Italy
    • Azienda Ospedaliera Universitaria - Ospedali Riuniti Foggia
  • Forlì, Italy
    • Ospedale C.G.Morgagni
  • Grosseto, Italy
    • Ospedale Misericordia
  • Gubbio, Italy
    • Ospedale Gualdo Tadino
  • Legnano, Italy
    • Ospedale Civile di Legnano
  • Melegnano, Italy
    • Ospedale di Vizzolo Predabissi
  • Milano, Italy
    • Ospedale San Paolo
  • Milano, Italy
    • Mario Negri
  • Negrar, Italy
    • Ospedale Sacro Cuore Don Calabria
  • Orbassano, Italy
    • Ospedale San Luigi Gonzaga
  • Osio Sotto, Italy
    • Policlinico San Marco
  • Palermo, Italy
    • Villa Sofía, Palermo
  • Passirana, Italy
    • P.O. di Passirana
  • Piacenza, Italy
    • Ospedale G. da Saliceto ,Piacenza
  • Ravenna, Italy
    • Ospedalel Santa Maria delle Croci
  • Reggio Emilia, Italy
    • Arcispedale S. Maria Nuova
  • Rimini, Italy
    • Ospedale infermi di Rimini
  • Roma, Italy
    • San Filippo Neri
  • Saronno, Italy
    • Presidio Ospedaliero di Saronno
  • Scorrano, Italy
    • Ospedale Veris Delli Ponti
  • Seriate, Italy
    • Ospedale Bolognini
  • Treviglio, Italy
    • Ospedale di Treviglio
  • Udine, Italy
    • Ospedale di Udine
  • Foggia
    • San Severo, Foggia, Italy
      • Teresa Masselli Mascia
• Spain
  • Alava, Spain
    • Txagorritxu
  • Alcorcón, Spain
    • Fundacion Alcorcon
  • Alcoy, Spain
    • Virgen de los Lirios de Alcoy
  • Alicante, Spain
    • H. San Juan
  • Andújar, Spain
    • Hospital Alto del Gualdalquivir
  • Avilés, Spain
    • San Agustin
  • Barcelona, Spain
    • Hospital de La Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Universitario de Bellvitge
  • Barcelona, Spain
    • Centro Medico Teknon
  • Barcelona, Spain
    • Consorci Sanitari Integral
  • Barcelona, Spain
    • H. Vall d´Hebron
  • Barcelona, Spain
    • Clinic
  • Barcelona, Spain
    • Germans Trias I Pujol
  • Bilbao, Spain
    • Hospital de Basurto
  • Burgos, Spain
    • Hospital Universitario de Burgos
  • Cartagena, Spain
    • H. Santa Lucía
  • Córdoba, Spain
    • Hosptial Universitario Reina Sofia
  • Denia, Spain
    • Hospital de Denia
  • Elche, Spain
    • Hospital Universitario de Vinalopó
  • Elche, Spain
    • Hospital Universitario de Elche
  • Elda, Spain
    • H.Universitario de Elda
  • Ferrol, Spain
    • Hospital Arquitecto Macide
  • Galdakao, Spain
    • Hospital Galdakao Usansolo
  • Gijón, Spain
    • Cabueñes
  • Granada, Spain
    • Hospital San Cecilio
  • Granada, Spain
    • Hospital Virgen de las Nieves
  • Huelva, Spain
    • H.U Juan Ramón Jimenez
  • Jaén, Spain
    • Complejo Hospitalario Universitario de Jaen
  • La Coruña, Spain
    • Complejo Hospitalario Universitario A Coruña
  • Las Palmas De Gran Canaria, Spain
    • Complejo Hospitalario Universitario Insular Materno Infantil
  • Lerida, Spain
    • Hospital Universitario de Arnau de Vilanova
  • León, Spain
    • Hospital de León
  • Lugo, Spain
    • Lucus Augusti
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Hospital Clínico
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain
    • Clinica La Luz
  • Madrid, Spain
    • Hospital Quirón Pozuelo
  • Madrid, Spain
    • Ruber Internacional
  • Madrid, Spain
    • Ruber Juan Bravo
  • Madrid, Spain
    • CNIC
  • Manresa, Spain
    • Hospital de Manresa
  • Mieres, Spain
    • Hospital Alvarez Buylla
  • Murcia, Spain
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Málaga, Spain
    • Hospital Regional Universitario de Málaga
  • Móstoles, Spain
    • Rey Juan Carlos
  • Oviedo, Spain
    • Hospital Universitario Central Asturias
  • Palma De Mallorca, Spain
    • Son Espases
  • Pamplona, Spain
    • Complejo Hospitalario de Navarra
  • Pontevedra, Spain
    • Montecelo
  • Salamanca, Spain
    • Clinico Universitario de Salamanca
  • Santander, Spain
    • Marques de Valdecilla
  • Santiago De Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago
  • Sevilla, Spain
    • H. Virgen del Rocío
  • Sevilla, Spain
    • Virgen de la Macarena
  • Tarragona, Spain
    • Hospital Universitari Joan XXIII
  • Tarragona, Spain
    • Hospital Universitario Sant Joan de Reus
  • Tenerife, Spain
    • Complejo Hospitalario Universitario de Canarias
  • Tenerife, Spain
    • Hospital General de La Palma
  • Tenerife, Spain
    • Nuestra Señora de la Candelaria
  • Torrejón De Ardoz, Spain
    • Hospital Universitario De Torrejon
  • Torrevieja, Spain
    • Hospital Universitario de Torrevieja
  • Tortosa, Spain
    • H. Verge de la Cinta
  • Valdemoro, Spain
    • Hospital Infanta Elena
  • Valencia, Spain
    • Hospital La Fe
  • Valencia, Spain
    • Hospital Clínico
  • Valencia, Spain
    • Hospital Universitario Doctor Peset
  • Valencia, Spain
    • IMED Valencia
  • Valladolid, Spain
    • Hospital Clínico Universitario de Valladolid
  • Valladolid, Spain
    • Río Hortega
  • Vigo, Spain
    • Alvaro Cunqueiro
  • Villalba, Spain
    • Hospital General de Villalba
  • Zaragoza, Spain
    • Miguel Servet
  • Úbeda, Spain
    • San Juan de la Cruz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years old
• Admitted for STEMI or NSTEMI and invasive management (i.e. coronary angiography during index hospitalization).
• LVEF>40% as evaluated by any imaging technique anytime during hospitalization.
• Signed informed consent

Exclusion Criteria:

• Known allergy or intolerance to beta-blockers
• Absolute contraindication to beta-blocker therapy according to treating physician judge
• Prior history of HF, Killip class on admission or during hospitalization ≥ II
• Severe valvular heart disease (> 3+ for aortic or mitral insufficiency, aortic or mitral valve area ≤1.0 cm2).
• Any condition (appart from AMI) that requires beta-blocker prescription on discharge according to treating physician judge
• Any medical condition that, in the investigator´s judgment, would seriously limit life expectancy (less than one year),
• Patients participating in other clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beta-blocker therapy; This is a strategy (pragmatic) trial. In patients allocated to "Beta-blocker therapy", beta blocker agent and dose are decided by treating physician. betablocker therapy chosen might be any of the following: atenolol bisoprolol carvedilol metoprolol nebivolol	Drug: Beta blocker; long-term maintenance beta-blocker therapy; Other Names: atenolol, bisoprolol, carvedilol, metoprolol, nevibolol.
No Intervention: Control (no beta-blocker therapy).; Do not receive beta -blocker therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of the composite of "all-cause death, nonfatal reinfarction, or heart failure hospitalization" (MACE)	absolute number of patients experiencing deaths will be added to number of patients experiencing a non fatal reinfarction and to number of patients experiencing heart failure hospitalization. If a patient experience more than one of these events, only first event will be added for the sum of events EXAMPLE events in arm 1: 150 deaths+150 reinfarctions+150 heart failure hospitalizations= TOTAL 450 MACE (450 events/4234 patients enroled: event rate 10.63%)	12-54 months since the beginning (median follow up anticipated 3.75 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2.1 Incidence rate of individual components of the primary outcome. 2.2 Incidence rate of cardiac mortality. 2.3 Incidence of sustained ventricular tachycardia/ventricular fibrillation (VT/VF) and resuscitated cardiac arrest.	Absolute number of events (% from total patients recruited) of the components of the MACE (eg number of all cause deaths (% from patients included) in active arm vs control). First event of each individual component counts for secondary outcome. EXAMPLE all cause death events in in arm 1: 200 deaths (200 events/4234 patients enroled: event rate 4.72%). nonfatal reinfarctions in in arm 1: 150 reinfarctions (150 events/4234 patients enroled: event rate 3.54%). note that in the example of the primary outcome, only 150 deaths are counted and for the secondary outcome 200. This is because in this hypothetical case, 50 deaths occurred in patients who previously experienced a nonfatal reinfarction	12-54 months since the beginning (median follow up anticipated 3.75 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
3.1 Incidence of revascularizations during follow-up 3.2 Composite of cardiac death, stroke or myocardial infarction. 3.3 Safety endpoints 3.4 Quality of life and functional status (telephone evaluation):	3.1: Absolute number of patients undergoing a revascularization procedure during follow-up (% from total patients recruited) note: revascularizations that were scheduled at patients' discharge inclusion WILL NOT be considered an event 3.2: absolute number of patients experiencing cardiac death will be added to number of patients experiencing a stroke and to number of patient experiencing a non fatal reinfarction. If a patient experience more than one of these events, only first event will be added for the sum of events 3.3 3.3.1: Incidence of admission for symptomatic advanced atrioventricular (AV) block (Mobitz II or third degree). Absolute number of patients admitted for symptomatic AV block (% from total patients recruited) 3.3.2: Incidence of hospital admission for stroke: Absolute number of patients admitted for a stroke during follow-up (% from total patients recruited) 3.4 EQ-5D questionnaire (0-100, 100 best) IIEF-5 quest (5-25, 25 best) PHQ-2 questionnaire (0-6, 6 worst)	12-54 months since the beginning (median follow up anticipated 3.75 years)

Collaborators and Investigators

• Sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Investigators: Principal Investigator: Borja Ibañez, MD PhD FESC, CNIC

Publications and helpful links

General Publications

• Rossello X, Raposeiras-Roubin S, Latini R, Dominguez-Rodriguez A, Barrabes JA, Sanchez PL, Anguita M, Fernandez-Vazquez F, Pascual-Figal D, De la Torre Hernandez JM, Ferraro S, Vetrano A, Perez-Rivera JA, Prada-Delgado O, Escalera N, Staszewsky L, Pizarro G, Aguero J, Pocock S, Ottani F, Fuster V, Ibanez B; REBOOT-CNIC investigators. Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT). Eur Heart J Cardiovasc Pharmacother. 2022 May 5;8(3):291-301. doi: 10.1093/ehjcvp/pvab060.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; Myocardial Infarction; Infarction; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Membrane Transport Modulators; Antioxidants; Protective Agents; Adrenergic Agents; Calcium Channel Blockers; Vasodilator Agents; Antihypertensive Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol; Metoprolol; Atenolol; Bisoprolol; Adrenergic beta-Antagonists
• Other Study ID Numbers: REBOOT-CNIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No