Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study Protocol for the FRAGILE Multicenter Randomized Controlled Trial

Abstract

IntroductionAdvances in modern medicine have led to people living longer and healthier lives. Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. When it comes to CABG surgery, randomized controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients. Therefore, we believe that off-pump CABG could be an important technique in patients with limited functional capacity to respond to surgical stress. In this study, the authors introduce the new national, multicenter, randomized, controlled trial "FRAGILE", to be developed in the main cardiac surgery centers of Brazil, to clarify the potential benefit of off-pump CABG in frail patients.MethodsFRAGILE is a two-arm, parallel-group, multicentre, individually randomized (1:1) controlled trial which will enroll 630 patients with blinded outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which aims to compare adverse cardiac and cerebrovascular events after off-pump versus on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention. Secondary outcomes will be major adverse cardiac and cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic shock, new onset of atrial fibrillation, renal replacement therapy, reoperation for bleeding, pneumonia, length of stay in intensive care unit, length of stay in hospital, number of units of blood transfused, graft patency, rate of complete revascularization, neurobehavioral outcomes after cardiac surgery, quality of life after cardiac surgery and costs.DiscussionFRAGILE trial will determine whether off-pump CABG is superior to conventional on-pump CABG in the surgical treatment of pre-frail and frail patients.Trial registrationClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated on March 21st 2016.

The Emblematic Year of 2011, Trials and the 50 Years of Heart Transplantation: Three Relevant Issues

“…The authors pointed out that these findings are strongly relevant and contribute to understanding whether the extent of premorbid deficit accumulation adds prognostic value after cardiovascular surgery. In this scenario, BJCVS was chosen by Mejía et al [ 2 ] as a vehicle for the publication of the study protocol of the randomized controlled multicenter FRAGILE trial, whose primary purpose will be to compare adverse cardiac and cerebrovascular events after CABG (on-pump vs. off-pump) in pre-frail and frail patients, inaugurating this new type of publication in our medical journal (page 428).…”

Impacto Atual da Circulação Extracorpórea na Cirurgia de Revascularização Miocárdica no Estado de São Paulo

“…[5][6][7] Assim, embora existam critérios bem-definidos para indicação da CRM, a escolha da CEC continua sendo baseada no perfil clínico do paciente e na experiência do cirurgião. A oportunidade atual para a técnica sem CEC pode estar no aumento de pacientes frágeis encaminhados para CRM, 8 no conceito de levar o procedimento correto para o paciente correto. Por outro lado, resultados atuais da CRM com CEC mostram uma diminuição da ocorrência de acidente vascular encefálico (AVE), 9 embora problemas com o aumento de sangramento e disfunção renal ainda persistam em pacientes de alto risco.…”

Aging and Frailty in Cardiac Surgery

“…Kardiyak cerrahi öncesinde kırılganlığın değerlendirildiği Frailty ABCs çalışmasında da, 5 metre yürüme hızının düşük olmasının postoperatif dönemde 3 kat artmış mortalite ve morbidite ile ilişkili olduğu belirtilmektedir [30] . Preoperatif dönemde değerlendirilen farklı frailite modellerinin 30 günlük, 1 ve 2 yıllık takipteki mortaliteyi öngörebildikleri çeşitli çalışmalarda göze çarpmaktadır [31][32][33] . Frail olan kişilerin operasyon sonrasında daha uzun süre hastanede kaldıkları, hızlı taburcu olmak istemedikleri, daha fazla rehabilitasyon istedikleri ortaya koyulmaktadır [33] .…”

“…Preoperatif dönemde değerlendirilen farklı frailite modellerinin 30 günlük, 1 ve 2 yıllık takipteki mortaliteyi öngörebildikleri çeşitli çalışmalarda göze çarpmaktadır [31][32][33] . Frail olan kişilerin operasyon sonrasında daha uzun süre hastanede kaldıkları, hızlı taburcu olmak istemedikleri, daha fazla rehabilitasyon istedikleri ortaya koyulmaktadır [33] .…”