Off Pump Versus On Pump Coronary Artery Bypass Grafting in Frailty Patients (FRAGILE)
Information source: University of Sao Paulo General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Coronary Artery Disease; Complications Due to Coronary Artery Bypass Graft; Fragility
Intervention: OPCAB (Procedure); CABG (Procedure)
Phase: N/A
Status: Not yet recruiting
Sponsored by: University of Sao Paulo General Hospital Official(s) and/or principal investigator(s): Luis Alberto O Dallan, MD, PhD, Study Chair, Affiliation: Heart Institute of São Paulo Medical School
Overall contact: Omar Mejia, MD, Phone: 55-11-26615000, Ext: 5014, Email: omarvmejia@gmail.com
Summary
The purpose of this study is to determine whether off-pump coronary artery bypass graft
(OPCAB) surgery is superior to conventional on-pump coronary artery bypass graft (CABG)
surgery in the treatment of Pre-frailty and Frailty patients
Clinical Details
Official title: Off Pump Versus On Pump Coronary Artery Bypass Grafting in Frailty Patients: A National, Multicenter, Prospective, Randomized Clinical Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: The primary purpose of this study is to compare adverse cardiac and cerebrovascular events after OPCAB and CABG in pre-frailty and frailty patients
Secondary outcome: Major Adverse Cardiac and Cerebrovascular events after OPCAB and CABG in pre-frailty and frailty patientsMajor Adverse Cardiac and Cerebrovascular events after OPCAB and CABG in pre-frailty and frailty patients Major Adverse Cardiac and Cerebrovascular events after OPCAB and CABG in pre-frailty and frailty patients Operative Time Mechanical Ventilation Time Hyperdynamic Shock New Onset of Atrial Fibrillation Need for Pacing >24 hours Renal Replacement Therapy Reoperation for Bleeding Pneumonia Length of Stay in Intensive Care Unit Length of Stay in Hospital Transfusion Requirement Graft Patency Clinical and Angiographic Scores Correlation with Prognostic Recurrence of Angina Rate of Complete Revascularization
Detailed description:
One of the most controversial areas of cardiac surgery has been whether off-pump coronary
artery bypass graft (OPCAB) surgery is superior to conventional on-pump coronary artery
bypass graft (CABG) surgery. There is an ongoing debate about the benefits and disadvantage
of OPCAB. Initial trials have shown that OPCAB is feasible in selected low-risk patients and
offers results similar to CABG. In institutions with experience in OPCAB, the rate of major
adverse events and the rates of complete revascularization and graft patency have been
similar to those with CABG. These positive results have been called into question by reports
of inferior graft patency and higher rates of repeat target-vessel revascularization
associated with OPCAB. The Randomized On/Off Bypass (ROOBY) trial showed that among low-risk
patients, the rate of death or major adverse events at 30 days after surgery was similar
with OPCAB and CABG, but OPCAB was associated with a higher rate of incomplete
revascularization at 1 year. Short-term mortality and morbidity after OPCAB and CABG were
similar in a recent trial involving 4752 patients with a mixed operative-risk profile in the
CABG Off or On Pump Revascularization Study (CORONARY). The German Off-Pump Coronary Artery
Bypass Grafting in Elderly Patients (GOPCABE) study focused exclusively on patients ≥ 75
years. However, this trial wouldn't elucidate the potential benefit of OPCAB in high-risk
patients because of this specific group of Germans patients were moderate-risk patients. The
results of the Best Bypass Surgery Trial (BBS), performed on 341 high-risk patients
(European system for cardiac operative risk evaluation "EuroSCORE" >5) undergoing CABG or
OPCAB, report no significant differences in the composite of adverse cardiac and
cerebrovascular events or in any of the following outcomes: All-cause mortality, acute
myocardial infarction, cardiac arrest, low cardiac output/cardiogenic shock, stroke, and
coronary re-intervention. However, in our opinion, the definition of high-risk patient
should be interpreted carefully. Although the EuroSCORE identifies patients based on 18
independent variables, many of which were not considered in the study. Risk factors such as
previous cardiac surgery, critical preoperative state, emergency operation, and poor left
ventricular dysfunction were excluded.
In the real world, with more than 1500 patients, Heart Institute researchers at the
University of São Paulo, showed lower mortality among patients operated OPCAB. So, after a
certain cutoff EuroSCORE > 4. 5 or 2000 Bernstein-Parsonnet score >17. 75, OPCAB significantly
reduces the chances of operative mortality. Indeed, numerous large retrospective studies and
meta-analyses have shown significant short-term improvements after OPCAB and comparable
long-term outcomes. A recent risk-adjusted analysis of the national Society of Thoracic
Surgeons database assessing 876081 patients demonstrated a significant reduction in death
and stroke (11% and 34% reduction, respectively) after OPCAB. After that, it is important to
reconsider the best approach for patients with higher surgical risk for CABG. Clearly a base
is being built with strong scientific evidence that this is the group that experiments the
most benefit from OPCAB. This could change the focus in relation to the use of
cardiopulmonary bypass in coronary artery bypass surgery, as well as the preference for
complete revascularization and the use of arterial grafts, especially in extremely high risk
patients.
Really, randomized, controlled trials have failed to demonstrate a significant mortality
benefit for OPCAB. However, the available randomized, controlled trials were underpowered to
detect significant differences between rarely events such as stroke or death and can suffer
from high selection and exclusion of biases. Even more important is the fact that available
randomized, controlled trials so far have primarily focused only on low-risk (ROOBY,
CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS) but not frailty patients in
whom the benefits of OPCAB should be well defined. Investigators believe that avoiding
cardiopulmonary bypass should be viewed primarily as a step toward avoiding aortic
manipulation. Despite the long-term benefits of surgery, some patients may choose
percutaneous coronary intervention for the treatment of complex multivessel disease to avoid
the morbidity associated with CABG, of which stroke is the most feared. Expert OPCAB
surgeons can offer equivalent durability of graft patency as in CABG, with a lower rate of
stroke if aortic manipulation is avoided.
Cardiac Risk Scores, including EuroSCORE and STS, have been developed to predict the risk of
adverse outcomes following surgery. Frailty, an independent predictor of mortality and
complications, is not included in these risk algorithms. Emerging evidence suggests that
frailty is a better marker of biological age and more important than chronological age.
Afilalo et al. determined that patients with slow preoperative gait speed (≥6 s to walk 5 m)
had a 2 to 3 fold increased risk of mortality and major morbidity for any given level of
STS-Predicted Risk of Mortality or Major Morbidity (PROM) compared with normal speed. Lee et
al. performed a retrospective review of a large cardiac registry, comparing outcomes between
non-frail and frail individuals. Frailty was an independent risk factor for in-hospital
mortality (risk-adjusted odds ratio [OR] 1. 8; 95% confidence interval [CI] 1. 1-3. 0; P =
0. 03) and mortality at 2 years (risk-adjusted hazards ratio [HR] 1. 5, 95% CI 1. 1-2. 2; P =
0. 01). The benefits of coronary artery bypass grafting without cardiopulmonary bypass in
Pre-frailty and Frailty patients are still undetermined.
Investigators believe OPCAB remains an important technique for the improvement of coronary
surgery. The question right now is: Pre-frailty and Frailty patients will benefit more from
OPCAB or CABG? The aim of this paper was clarify the potential benefit of OPCAB in
Pre-frailty and Frailty patients, Investigators conducted a national, multicenter,
controlled, randomized clinical trial comparing OPCAB versus CABG in FRAGIL trial.
Eligibility
Minimum age: 65 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients who will be scheduled for isolated, first-time CABG must be eligible if they
will be at least 65 years of age and should be pre-frailty or frailty status
according the Fried Frailty Criteria
Exclusion Criteria:
- Any additional cardiovascular disease necessitating concomitant surgery, previous
pericardiotomy, any condition requiring immediate surgery (i. e., within 24 hours
after hospital admission), planned minimally invasive direct coronary-artery bypass
procedure (CABG with the use of left anterior thoracotomy), and the inability or
unwillingness of the patient to provide consent.
Locations and Contacts
Omar Mejia, MD, Phone: 55-11-26615000, Ext: 5014, Email: omarvmejia@gmail.com
USP Heart Institute, São Paulo, Brazil; Not yet recruiting Omar AV Mejia, MD, Phone: 11-996862043, Email: omarvmejia@gmail.com Luiz AF Lisboa, MD, PhD, Phone: 11-994445829, Email: luiz.lisboa@incor.usp.br Omar Asdrúbal V Mejía, MD, Principal Investigator Luiz Augusto F Lisboa, MD, PhD, Principal Investigator Fabio B Jatene, MD, PhD, Principal Investigator Luís Roberto P Dallan, MD, Sub-Investigator Fernando A Atik, MD, PhD, Sub-Investigator Orlando Petrucci Junior, MD, PhD, Sub-Investigator Walter Gomes, MD, PhD, Sub-Investigator Marco Antonio P Oliveira, MD, Sub-Investigator Ricardo C Lima, MD, PhD, Sub-Investigator Rodrigo C Segalote, MD, Sub-Investigator Rodrigo M Milani, MD, Sub-Investigator Alexandre C Hueb, MD, PhD, Sub-Investigator Maurilio O Deininger, MD, PhD, Principal Investigator Gustavo CA Ribeiro, MD, PhD, Sub-Investigator Marcelo M Cascudo, MD, Sub-Investigator Roberto Rocha e Silva, MD, PhD, Sub-Investigator Ludhmila A Hajjar, MD, PhD, Sub-Investigator Filomena Regina G Galas, MD, PhD, Sub-Investigator Luiz Antonio M César, MD, PhD, Sub-Investigator José C Nicolau, MD, PhD, Sub-Investigator Humberto Pierri, MD, PhD, Sub-Investigator Roberto Kalil Filho, MD, PhD, Sub-Investigator Leandro Batisti de Faria, MD, Sub-Investigator
Additional Information
Foundation for Research Support of the State of São Paulo Zerbini Foundation Brazilian Cardiovascular Society
Starting date: August 2015
Last updated: April 10, 2015
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