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: Recruiting
• 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 (Estimated): 8468
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Borja Ibañez, MD PhD FESC; Phone Number: 4302 914501200; Email: bibanez@cnic.es
• Study Contact Backup: Name: Noemi Escalera; Phone Number: 5401 914501200; Email: nescalera@cnic.es

Study Locations

• Italy
  • Alessandria, Italy
    • Recruiting
    • Ospedale Civile Santi Antonio e Biagio
    • Contact: Gianfranco Pistis
  • Ancona, Italy
    • Recruiting
    • Azienda Ospedaliero Universitaria Ospedali Riuniti
    • Contact: Gianpiero Perna
  • Baggiovara, Italy
    • Recruiting
    • Ospedale Civile
    • Contact: Stefano Tondi
  • Bari, Italy
    • Recruiting
    • Ospedale San Paolo
    • Contact: Nicola Locuratolo
  • Bologna, Italy
    • Recruiting
    • Ospedale Maggiore
    • Contact: Gianni Casella
  • Caserta, Italy
    • Recruiting
    • A.O. Sant'Anna e San Sebastiano di Caserta
    • Contact: Alfredo Vetrano
  • Cortona, Italy
    • Recruiting
    • Santa Margherita
    • Contact: Franco Cosmi
  • Cremona, Italy
    • Recruiting
    • Ospedale di Cremona
    • Contact: GB Danzi
  • Desio, Italy
    • Recruiting
    • Ospedale di Desio
    • Contact: Nadia Mollichelli
  • Fidenza, Italy
    • Recruiting
    • Ospedale di Vaio
    • Contact: Giovanni Tortorella
  • Foggia, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria - Ospedali Riuniti Foggia
    • Contact: Natale Brunetti
  • Forlì, Italy
    • Recruiting
    • Ospedale C.G.Morgagni
    • Contact: Filippo Ottani, MD PhD; Email: ottanif@alice.it
    • Principal Investigator: Filippo Ottani, MD PhD
  • Grosseto, Italy
    • Recruiting
    • Ospedale Misericordia
    • Contact: Marco Solari
  • Gubbio, Italy
    • Recruiting
    • Ospedale Gualdo Tadino
    • Contact: Deborah Cosmi
  • Legnano, Italy
    • Recruiting
    • Ospedale Civile di Legnano
    • Contact: Fabrizio Poletti
  • Melegnano, Italy
    • Recruiting
    • Ospedale di Vizzolo Predabissi
    • Contact: Filippo Ottani
  • Negrar, Italy
    • Recruiting
    • Ospedale Sacro Cuore Don Calabria
    • Contact: Andrea Chiampan
    • Principal Investigator: Andrea Chiampan
  • Orbassano, Italy
    • Recruiting
    • Ospedale San Luigi Gonzaga
    • Contact: Laura Montagna
  • Osio Sotto, Italy
    • Recruiting
    • Policlinico San Marco
    • Contact: Nicoletta De Cesare
  • Palermo, Italy
    • Recruiting
    • Villa Sofía, Palermo
    • Contact: Mario Lombardi
  • Passirana, Italy
    • Recruiting
    • P.O. di Passirana
    • Contact: Elena Martinoli
  • Piacenza, Italy
    • Recruiting
    • Ospedale G. da Saliceto ,Piacenza
    • Contact: Giovanni Quinto
  • Ravenna, Italy
    • Recruiting
    • Ospedalel Santa Maria delle Croci
    • Contact: Andrea Rubboli
  • Reggio Emilia, Italy
    • Recruiting
    • Arcispedale S. Maria Nuova
    • Contact: Alessandro Navazio
  • Rimini, Italy
    • Recruiting
    • Ospedale Infermi di Rimini
    • Contact: Barbara Valentini
  • Roma, Italy
    • Recruiting
    • San Filippo Neri
    • Contact: Stefania Di Fusco
  • Saronno, Italy
    • Recruiting
    • Presidio Ospedaliero di Saronno
    • Contact: Daniele Nassiacos
  • Scorrano, Italy
    • Recruiting
    • Ospedale Veris Delli Ponti
    • Contact: Eugenio Vilei
  • Seriate, Italy
    • Recruiting
    • Ospedale Bolognini
    • Contact: Alessandra Costalunga
  • Treviglio, Italy
    • Recruiting
    • Ospedale di Treviglio
    • Contact: Paolo Sganzerla
  • Foggia
    • San Severo, Foggia, Italy
      • Recruiting
      • Teresa Masselli Mascia
      • Contact: Francesca Miscio
• Spain
  • Alava, Spain
    • Recruiting
    • Txagorritxu
    • Contact: Alfonso Torres
  • Alcorcón, Spain
    • Recruiting
    • Fundacion Alcorcon
    • Contact: Javier Botas
  • Alcoy, Spain
    • Recruiting
    • Virgen de los Lirios de Alcoy
    • Contact: Guillermo Grau
  • Andújar, Spain
    • Recruiting
    • Hospital Alto del Gualdalquivir
    • Contact: Carmen Rus
  • Avilés, Spain
    • Recruiting
    • San Agustin
    • Contact: Roi Bangueses
  • Barcelona, Spain
    • Recruiting
    • Hospital de La Santa Creu i Sant Pau
    • Contact: Alessandro Sionis
  • Barcelona, Spain
    • Recruiting
    • Centro Medico Teknon
    • Contact: Jordi Palet
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitario de Bellvitge
    • Contact: Albert Ariza
  • Barcelona, Spain
    • Recruiting
    • Clinic
    • Contact: Manel Sabate
  • Barcelona, Spain
    • Recruiting
    • Consorci Sanitari Integral
    • Contact: Roman Freixa
  • Barcelona, Spain
    • Recruiting
    • Germans Trias I Pujol
    • Contact: Cosme García
  • Barcelona, Spain
    • Recruiting
    • H. Vall d´Hebron
    • Contact: Jose A. Barrabes
  • Bilbao, Spain
    • Recruiting
    • Hospital de Basurto
    • Contact: Abel Andres
  • Burgos, Spain
    • Recruiting
    • Hospital Universitario de Burgos
    • Contact: Jose Angel Perez
  • Cartagena, Spain
    • Recruiting
    • H. Santa Lucía
    • Contact: Isidro Hernandez
  • Córdoba, Spain
    • Recruiting
    • Hosptial Universitario Reina Sofia
    • Contact: Manuel Anguita
  • Denia, Spain
    • Recruiting
    • Hospital de Denia
    • Contact: Alfonso Valle
  • Elche, Spain
    • Recruiting
    • Hospital universitario de Elche
    • Contact: Pedro Morillas
  • Elche, Spain
    • Recruiting
    • Hospital Universitario de Vinalopo
    • Contact: Eduardo Arroyo
  • Elda, Spain
    • Recruiting
    • H.Universitario de Elda
    • Contact: Hugo Paris
  • Ferrol, Spain
    • Recruiting
    • Hospital Arquitecto Macide
    • Contact: Alejandro Rodriguez
  • Galdakao, Spain
    • Recruiting
    • Hospital Galdakao Usansolo
    • Contact: Gonzalo Navarrete
  • Gijón, Spain
    • Recruiting
    • Cabueñes
    • Contact: Iñigo Lozano
  • Granada, Spain
    • Recruiting
    • Hospital San Cecilio
    • Contact: Concha Correa
  • Granada, Spain
    • Recruiting
    • Hospital Virgen de las Nieves
    • Contact: Jose Antonio Ramirez
  • Jaén, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Jaen
    • Contact: Rosa Fernandez
  • La Coruña, Spain
    • Recruiting
    • Complejo Hospitalario Universitario A Coruña
    • Contact: Jose M Vazquez
  • Las Palmas De Gran Canaria, Spain
    • Recruiting
    • Complejo Hospitalario Universitario Insular Materno Infantil
    • Contact: Efrén Martinez
  • Lerida, Spain
    • Recruiting
    • Hospital Universitario de Arnau de Vilanova
    • Contact: Tomás Querol
  • León, Spain
    • Recruiting
    • Hospital de Leon
    • Contact: Felipe Fernandez
  • Lugo, Spain
    • Recruiting
    • Lucus Augusti
    • Contact: Carlos Juanatey
  • Madrid, Spain
    • Recruiting
    • Hospital Gregorio Marañón
    • Contact: Francisco Fernadez Aviles
  • Madrid, Spain, 28040
    • Recruiting
    • Fundacion Jimenez Diaz University Hospital
    • Contact: Sandra Gomez-Talavera, MD; Email: sandra.gomezt@quironsalud.es
    • Contact: María Lopez-Alvarez, RN; Email: mlalvarez@quironsalud.es
    • Principal Investigator: Borja Ibanez, MD PhD FESC
  • Madrid, Spain
    • Recruiting
    • Hospital 12 de Octubre
    • Contact: Hector Bueno
  • Madrid, Spain
    • Recruiting
    • Clinica La Luz
    • Contact: Roberto Martin Reyes
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico
    • Contact: Antonio Fernandez Ortiz
  • Madrid, Spain
    • Recruiting
    • Hospital Quirón Pozuelo
    • Contact: Ines García Lunar
  • Madrid, Spain
    • Recruiting
    • Ruber Internacional
    • Contact: Eduardo Alegria
  • Madrid, Spain
    • Recruiting
    • Ruber Juan Bravo
    • Contact: Gonzalo Pizarro
  • Manresa, Spain
    • Recruiting
    • Hospital de Manresa
    • Contact: Gabriel Vazquez
  • Mieres, Spain
    • Recruiting
    • Hospital Alvarez Buylla
    • Contact: Alfredo Renilla
  • Murcia, Spain
    • Recruiting
    • Hospital Clínico Universitario Virgen de la Arrixaca
    • Contact: Domingo Pascual
  • Málaga, Spain
    • Recruiting
    • Hospital Regional Universitario de Malaga
    • Contact: Manuel de Mora
  • Móstoles, Spain
    • Recruiting
    • Rey Juan Carlos
    • Contact: Petra Sanz
  • Oviedo, Spain
    • Recruiting
    • Hospital Universitario Central Asturias
    • Contact: Jose Rozado
  • Palma De Mallorca, Spain
    • Recruiting
    • Son Espases
    • Contact: Jaume Pons
  • Pamplona, Spain
    • Recruiting
    • Complejo Hospitalario de Navarra
    • Contact: Pablo Bazal
  • Pontevedra, Spain
    • Recruiting
    • Montecelo
    • Contact: Oscar Díaz
  • Salamanca, Spain
    • Recruiting
    • Clinico Universitario de Salamanca
    • Contact: Pedro Luis Sanchez
  • Santander, Spain
    • Recruiting
    • Marques de Valdecilla
    • Contact: Jose María de la Torre
  • Santiago De Compostela, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Santiago
    • Contact: J Ramon Juanatey
  • Sevilla, Spain
    • Recruiting
    • H. Virgen del Rocio
    • Contact: Ana Maria Campos
  • Sevilla, Spain
    • Recruiting
    • Virgen de la Macarena
    • Contact: Rafael Hidalgo
  • Tarragona, Spain
    • Recruiting
    • Hospital Universitario Sant Joan de Reus
    • Contact: Josep M Alegret
  • Tarragona, Spain
    • Recruiting
    • Hospital Universitari Joan Xxiii
    • Contact: Alfredo Bardaji
  • Tenerife, Spain
    • Recruiting
    • Complejo hospitalario Universitario de Canarias
    • Contact: Alberto Dominguez
  • Tenerife, Spain
    • Recruiting
    • Hospital General de La Palma
    • Contact: Ricardo Jose Jaimes Vivas
  • Tenerife, Spain
    • Recruiting
    • Nuestra Señora de la Candelaria
    • Contact: Julio Hernandez
  • Torrejón De Ardoz, Spain
    • Recruiting
    • Hospital Universitario de Torrejon
    • Contact: Juan Ruiz
  • Torrevieja, Spain
    • Recruiting
    • Hospital Universitario de Torrevieja
    • Contact: Francisco Torres
  • Tortosa, Spain
    • Recruiting
    • H. Verge de la Cinta
    • Contact: Delicia Gentille
  • Valdemoro, Spain
    • Recruiting
    • Hospital Infanta Elena
    • Contact: Petra Sanz
  • Valencia, Spain
    • Recruiting
    • Hospital La Fe
    • Contact: Jaume Aguero
  • Valencia, Spain
    • Recruiting
    • Hospital Universitario Doctor Peset
    • Contact: Vicente Mora
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico
    • Contact: Juan Sanchis
  • Valencia, Spain
    • Recruiting
    • IMED Valencia
    • Contact: Oscar Fabregat
  • Valladolid, Spain
    • Recruiting
    • Hospital Clínico Universitario de Valladolid
    • Contact: Alberto San Roman
  • Valladolid, Spain
    • Recruiting
    • Río Hortega
    • Contact: Maria Jesus Rollan
  • Vigo, Spain
    • Recruiting
    • Alvaro Cunqueiro
    • Contact: Sergio Raposeiras
  • Villalba, Spain
    • Recruiting
    • Hospital General de Villalba
    • Contact: Felipe Navarro
  • Xàtiva, Spain
    • Recruiting
    • Hospital de Xativa
    • Contact: Jorge Sanchez Torrijos
  • Zaragoza, Spain
    • Recruiting
    • Miguel Servet
    • Contact: Rosario Ortas
  • Úbeda, Spain
    • Recruiting
    • San Juan de la Cruz
    • Contact: Juan Luis Bonilla

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
1) Incidence rate of individual components of the primary outcome. 2) Incidence rate of cardiac mortality.	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
1) Incidence of subsequent revascularizations. 2) Incidence of ICD (including CRT) insertion.	absolute number of events (% from total patients recruited) in each treatment arm experiencing any of the components of the MACE. First event of each individual component counts for secondary outcome.	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 (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 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): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

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

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