Off-pump Versus On-pump Coronary Artery Bypass Grafting in Frail Patients

Study Overview
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Brief Summary
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Frailty is defined as a geriatric syndrome of impaired resiliency to stressors (such as cardiac surgery) that has been delineated recently in the cardiovascular literature. One of the most controversial areas of cardiac surgery has been whether off-pump coronary artery bypass grafting (OPCAB) surgery is superior to conventional on-pump coronary artery bypass grafting (CABG) surgery. There is an ongoing debate about the benefits and disadvantages of OPCAB surgery and we believe that this remains an important technique for the improvement of coronary surgery. The benefits of CABG surgery in frail patients are still undetermined. The aim of this study is to clarify the potential benefit of OPCAB surgery in pre-frail and frail patients by comparing off-pump versus on-pump CABG in these patients.

Detailed Description
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The FRAGILE protocol is a national multicenter randomized controlled trial (RCT), conducted in 8 Brazilian institutions. The study is already approved by a certified ethics committee. Funding is provided by a grant from São Paulo Research Foundation (FAPESP), which otherwise will not have any role in the conduct of the study nor in the analysis nor in the reporting of data. A confidentiality agreement regarding data use and the data safety will be monitored by an independent monitoring board. All the authors will provide revisions and comments and be testifying for the accuracy and completeness of the report, as well as for the fidelity of the report to the study protocol.

Official Title
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A Multicenter, Prospective, Randomized, Clinical Trial Comparing Off-pump Versus On-pump Coronary Artery Bypass Grafting in Frail Patients

Conditions
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Frail Elderly, Coronary Artery Disease

Intervention / Treatment
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* Procedure: Off-pump coronary-artery bypass grafting
* Procedure: On-pump coronary-artery bypass grafting


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - Participants aged ≥60 years with the indication of myocardial revascularization with ≥2 criteria of frailty by Fried Frailty Criteria, and suitable to undergo either Off-pump or On-pump CABG. Exclusion criteria: - Patients with the indication of angioplasty or another procedure in addition to CABG; patients who underwent an emergency operation (within 24 hours after hospital admission); patients who underwent previous cardiac surgery, even with other approaches than median sternotomy; patients who do not have free, prior and informed consent to participate in this study.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients will be randomly assigned to off-pump CABG or on-pump CABG procedure.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Off-pump coronary-artery bypass grafting - OPCAB<br>Pre-frail and frail patients will be randomly assigned to OPCAB after the evaluation of the target vessels by an internet-based, password protected database program. The surgery will be performed as described in the intervention section and the patients will be followed up for two years. | Procedure: Off-pump coronary-artery bypass grafting<br>* Surgical access to the heart will be gained through a median sternotomy in all of the patients. In order to reduce the risk of bleeding and transfusions, an absorbable hemostat will be used in the sternal bone marrow. An automatic autotransfusion system will be used to recovery of red blood cells in all patients. Off-pump surgery will be performed with the use of heart stabilizers. Patients will be heparinized with 250 IU/kg intravenously to achieve activated clotting time >200s. The proximal anastomosis will be performed according to our guidelines. The distal anastomosis will be constructed with the help of mechanical stabilizers and cardiac positioner. Intracoronary shunts will be used routinely.<br>* Other names: OPCAB;|
| Active Comparator: On-pump coronary-artery bypass grafting - CABG<br>Pre-frail and frail patients will be randomly assigned to CABG after the evaluation of the target vessels by an internet-based, password protected database program. The surgery will be performed as described in the intervention section and the patients will be followed up for two years. | Procedure: On-pump coronary-artery bypass grafting<br>* Surgical access to the heart will be gained through a median sternotomy in all of the patients. On-pump surgery will be performed in normothermia, with the use of aortic cross-clamping and cold cardioplegic arrest. Patients will be heparinized with 500 IU/kg to achieve an activated clotting time >480 s. Heparin will be neutralized with 1:1 protamine sulfate. The automatic autotransfusion system will be used just in massive blood loss to recovery the red blood cells. Surgical techniques will be performed according to our guidelines.<br>* Other names: CABG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac and cerebrovascular events after OPCAB and CABG in pre-frail and frail patients | This composite outcome comprises: all cause death, acute myocardial infarction, stroke, renal failure, acute respiratory distress syndrome and bleeding reoperation. | 30 days, 6 months, 1 and 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operative time | Operative time in minutes. | 30 days | 
| Mechanical ventilation time | Mechanical ventilation time in hours. | 30 days | 
| Hyperdynamic shock | A cluster of symptoms that signals the onset of septic shock, often including a shaking chill, rapid rise in temperature, flushing of the skin, galloping pulse, and alternating rise and fall of the blood pressure. | 30 days | 
| New onset of atrial fibrillation | 12-lead electrocardiography (ECG) to confirm the diagnosis of new onset atrial fibrillation. | 30 days | 
| Need for pacing >24 hours | Patient who requires pacing >24 hours. | 30 days, 6 months | 
| Renal replacement therapy | Any type of renal replacement therapy in a patient who does not make continued use of this. | 30 days, 6 months | 
| Reoperation for bleeding | Patient has to underwent a re-thoracotomy for bleeding arising from a previous surgery. | 30 days | 
| Pneumonia | Physician or advanced practitioner documents the diagnosis in the medical record based on laboratory findings (e.g. positive sputum culture results from transtracheal fluid and/or bronchial washings) and/or radiological evidence (e.g. chest radiograph diagnostic of pulmonary infiltrates). | 30 days, 6 months | 
| Length of stay in intensive care unit | Total time in hours in Intensive Care Unit. | 30 days, 6 months | 
| Length of stay in hospital | Total time in days in hospital. | 30 days, 6 months | 
| Transfusion requirement | Number of units of blood transfused. | 30 days | 
| Graft patency | Patency of grafts and coronary artery disease at 6 months of follow-up evaluated by angiotomography. | 6 months | 
| Clinical and angiographic scores correlation with prognostic | To evaluate the clinical correlation between the revascularization strategy and the usefulness of the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SYNTAX score); age, creatinine and ejection fraction score (ACEF score); clinical SYNTAX score; European System for Cardiac Operative Risk Evaluation (EuroSCORE II); The Society of Thoracic Surgeon´s risk model (STS score) and Índice de Predição do INStituto do CORação (InsCor) for prognostic evaluation. | 1 year | 
| Recurrence of angina | To analyse patient recurrence of angina according to the Canadian Cardiovascular Society (CCS). | 30 days, 6 months, 1 and 2 years | 
| Rate of complete revascularization | To evaluate and compare the rate of complete revascularization in each one of both strategies. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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On-pump, Frail elderly, Coronary artery bypass surgery, Off-pump, Randomized controlled trial