Rationale and design of the BUDAPEST-CRT Upgrade Study: a prospective, randomized, multicentre clinical trial

Bela Merkely, Annamaria Kosztin, Attila Roka, Laszlo Geller, Endre Zima, Attila Kovacs, Andras Mihaly Boros, Helmut Klein, Jerzy K Wranicz, Gerhard Hindricks, Marcell Clemens, Gabor Z Duray, Arthur J Moss, Ilan Goldenberg, Valentina Kutyifa, Bela Merkely, Annamaria Kosztin, Attila Roka, Laszlo Geller, Endre Zima, Attila Kovacs, Andras Mihaly Boros, Helmut Klein, Jerzy K Wranicz, Gerhard Hindricks, Marcell Clemens, Gabor Z Duray, Arthur J Moss, Ilan Goldenberg, Valentina Kutyifa

Abstract

Aims: There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF.

Methods and results: The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II-IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes.

Conclusion: The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing.

Clinical trials.gov identifier: NCT02270840.

Keywords: Cardiac resynchronization therapy upgrade; Dyssynchrony; Pacing-induced heart failure; Randomized controlled trial; Right ventricular pacing; Study design.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Study flowchart.

References

    1. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E et al. . Cardiac resynchronization in chronic heart failure. New Eng J Med 2002;346:1845–53.
    1. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T et al. . Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. New Eng J Med 2004;350:2140–50.
    1. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L et al. . The effect of cardiac resynchronization on morbidity and mortality in heart failure. New Eng J Med 2005;352:1539–49.
    1. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP et al. . Cardiac-resynchronization therapy for the prevention of heart-failure events. New Eng J Med 2009;361:1329–38.
    1. Bogale N, Witte K, Priori S, Cleland J, Auricchio A, Gadler F et al. . The European Cardiac Resynchronization Therapy Survey: comparison of outcomes between de novo cardiac resynchronization therapy implantations and upgrades. Eur J Heart Fail 2011;13:974–83.
    1. Poole JE, Gleva MJ, Mela T, Chung MK, Uslan DZ, Borge R et al. . Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE registry. Circulation 2010;122:1553–61.
    1. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310:2191–4.
    1. Wilkoff BL, Love CJ, Byrd CL, Bongiorni MG, Carrillo RG, Crossley GH 3rd et al. . Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management: this document was endorsed by the American Heart Association (AHA). Heart Rhythm 2009;6:1085–104.
    1. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA et al. . 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace 2013;15:1070–118.
    1. Ellenbogen KA, Gold MR, Meyer TE, Fernndez Lozano I, Mittal S, Waggoner AD et al. . Primary results from the SmartDelay determined AV optimization: a comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial: a randomized trial comparing empirical, echocardiography-guided, and algorithmic atrioventricular delay programming in cardiac resynchronization therapy. Circulation 2010;122:2660–8.
    1. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS et al. . 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013;61:e6–75.
    1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K et al. . ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33:1787–847.
    1. Russo AM, Stainback RF, Bailey SR, Epstein AE, Heidenreich PA, Jessup M et al. . ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy: a report of the American College of Cardiology Foundation appropriate use criteria task force, Heart Rhythm Society, American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. Heart Rhythm 2013;10:e11–58.
    1. Authors/Task Force M, Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J et al. . 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Europace 2015;17:1601–87.
    1. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL et al. . Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2003;107:2932–7.
    1. Sharma AD, Rizo-Patron C, Hallstrom AP, O'Neill GP, Rothbart S, Martins JB et al. . Percent right ventricular pacing predicts outcomes in the DAVID trial. Heart Rhythm 2005;2:830–4.
    1. Olshansky B, Day JD, Lerew DR, Brown S, Stolen KQ, Investigators IRS. Eliminating right ventricular pacing may not be best for patients requiring implantable cardioverter-defibrillators. Heart Rhythm 2007;4:886–91.
    1. Martinelli Filho M, de Siqueira SF, Costa R, Greco OT, Moreira LF, D'Avila A et al. . Conventional versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study. J Card Fail 2010;16:293–300.
    1. Yu CM, Fang F, Luo XX, Zhang Q, Azlan H, Razali O. Long-term follow-up results of the pacing to avoid cardiac enlargement (PACE) trial. Eur J Heart Fail 2014;16:1016–25.
    1. Essebag V, Joza J, Birnie DH, Sapp JL, Sterns LD, Philippon F et al. . Incidence, predictors, and procedural results of upgrade to resynchronization therapy: the RAFT upgrade substudy. Circ Arrhythm Electrophysiol 2015;8:152–8.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj