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

Coronary Artery Disease Clinical Trial

— FRAGILE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02338947
• Other study ID #: USaoPauloGH1000
• Secondary ID: Sao Paulo Resear
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2021
• Source: University of Sao Paulo General Hospital
• Contact: Omar AV Mejia, MD, PhD
• Phone: 55(11) 996862043
• Email: omar.mejia[@]incor.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 630
• Est. completion date: December 31, 2021
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Frail Elderly

Intervention

Procedure:
• Off-pump coronary-artery bypass grafting
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.
• On-pump coronary-artery bypass grafting
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.

Locations

Country	Name	City	State
Brazil	Hospital Samaritano Campinas	Campinas	SP
Brazil	Hospital Alberto Urquiza Wanderley	João Pessoa	Paraiba
Brazil	Hospital das Clínicas Samuel Libânio	Pouso Alegre	Minas Gerais
Brazil	Pronto Socorro Cardiológico de Pernambuco	Recife	Pernambuco
Brazil	Instituto Nacional de Cardiologia de Laranjeiras	Rio De Janeiro
Brazil	Beneficência Portuguesa de São Paulo	São Paulo
Brazil	Hospital Samaritano Paulista	São Paulo
Brazil	Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo	São Paulo
United States	Mount Sinai Hospital	New York	New York

Sponsors (10)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Beneficência Portuguesa de São Paulo, Hospital Alberto Urquiza Wanderley, Hospital das Clínicas Samuel Libânio, Hospital Samaritano Campinas, Hospital Samaritano Paulista, Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo, Instituto Nacional de Cardiologia de Laranjeiras, Mount Sinai Hospital, New York, Pronto-Socorro Cardiológico Universitário de Pernambuco

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neurobehavioral outcomes after cardiac surgery	To evaluate the global cognitive status a examination test will be performed included 30 simple questions and tasks in a number of areas (orientation in time and place, repeating and recalling list of words, arithmetic, language use and comprehension, non-verbal memory).	6 months, 1 year
Other	Quality of life after cardiac surgery	To evaluate the quality of life by the EuroQol-registration, a five domain and a visual analogue scale (VAS). The best state they can imagine is marked by 100 and the worst state marked by 0.	6 months, 1 year
Other	Cost	The adjusted amount in US dollars of the total cost of coronary artery bypass surgery for all participating hospitals will be evaluated.	2 years
Primary	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	Operative time	Operative time in minutes.	30 days
Secondary	Mechanical ventilation time	Mechanical ventilation time in hours.	30 days
Secondary	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
Secondary	New onset of atrial fibrillation	12-lead electrocardiography (ECG) to confirm the diagnosis of new onset atrial fibrillation.	30 days
Secondary	Need for pacing >24 hours	Patient who requires pacing >24 hours.	30 days, 6 months
Secondary	Renal replacement therapy	Any type of renal replacement therapy in a patient who does not make continued use of this.	30 days, 6 months
Secondary	Reoperation for bleeding	Patient has to underwent a re-thoracotomy for bleeding arising from a previous surgery.	30 days
Secondary	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
Secondary	Length of stay in intensive care unit	Total time in hours in Intensive Care Unit.	30 days, 6 months
Secondary	Length of stay in hospital	Total time in days in hospital.	30 days, 6 months
Secondary	Transfusion requirement	Number of units of blood transfused.	30 days
Secondary	Graft patency	Patency of grafts and coronary artery disease at 6 months of follow-up evaluated by angiotomography.	6 months
Secondary	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
Secondary	Recurrence of angina	To analyse patient recurrence of angina according to the Canadian Cardiovascular Society (CCS).	30 days, 6 months, 1 and 2 years
Secondary	Rate of complete revascularization	To evaluate and compare the rate of complete revascularization in each one of both strategies.	30 days

External Links

•   Brazilian Cardiovascular Society
•   São Paulo Research Foundation
•   Zerbini Foundation