Frail ElderlyFRAGILENCT02338947

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

A study testing Off-pump coronary-artery bypass grafting and On-pump coronary-artery bypass grafting in people with Frail Elderly and Coronary Artery Disease, run by University of Sao Paulo General Hospital at 7 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 60 years and olderHealthy volunteers can take part
Conditions the study is for: Frail Elderly, Coronary Artery Disease
What is being tested?: Off-pump coronary-artery bypass grafting and On-pump coronary-artery bypass grafting
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 440 participants
Where: 7 sitesin 2 countries
Study dates: 1 Jan 2019to 31 Dec 2025
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

Brazil6 sites

Hospital de Messejana
Fortaleza, Ceará
Hospital Alberto Urquiza Wanderley
João Pessoa, Paraíba, 58040-300
Hospital das Clínicas Samuel Libânio
Pouso Alegre, Minas Gerais, 37550-000
Instituto Nacional de Cardiologia de Laranjeiras
Rio de Janeiro, Rio de Janeiro, 22240-002
Beneficência Portuguesa de São Paulo
São Paulo, São Paulo, 01323-001
Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo
São Paulo, São Paulo, 05403-900

Other trials in Brazil

United States1 site

Emory University School of Medicine
Atlanta, Georgia, 30322

Other trials in United States

About this study

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

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.

Read the detailed description

The FRAGILE protocol is a national multicenter randomized controlled trial (RCT), conducted in 6 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.

Conditions: Frail Elderly, Coronary Artery Disease
Being tested: Off-pump coronary-artery bypass grafting, On-pump coronary-artery bypass grafting
Keywords: Frail elderly, Coronary artery bypass surgery, Off-pump, On-pump, Randomized controlled trial
Medical subject headings: Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Off-pump coronary-artery bypass graftingOther
Also called OPCAB
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 graftingOther
Also called CABG
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.

Study groups in NCT02338947
Study group	Role	What they receive
Off-pump coronary-artery bypass grafting - OPCAB	Active comparator	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. Receives: Other: Off-pump coronary-artery bypass grafting
On-pump coronary-artery bypass grafting - CABG	Active comparator	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. Receives: Other: On-pump coronary-artery bypass grafting

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days

Secondary outcomes (13)

Operative time
Operative time in minutes
Measured: From the start of anesthesia induction to the end of the surgical procedure
Mechanical ventilation time
Mechanical ventilation time in hours
Measured: From the initiation of mechanical ventilation in the operating room or ICU to the time of successful extubation
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
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days
New onset of atrial fibrillation
12-lead electrocardiography (ECG) to confirm the diagnosis of new onset atrial fibrillation.
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Need for pacing >24 hours
Patient who requires pacing >24 hours
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Renal replacement therapy
Any type of renal replacement therapy in a patient who does not make continued use of this
Measured: From the date of surgery until 30 days postoperatively, assessed up to 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)
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Length of stay in intensive care unit
Total time in hours in Intensive Care Unit
Measured: From the date of surgery until ICU discharge, assessed up to 30 days
Length of stay in hospital
Total time in days in hospital
Measured: From the date of surgery until hospital discharge, assessed up to 90 days
Transfusion requirement
Number of units of red blood cells transfused
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Recurrence of angina
To analyse patient recurrence of angina according to the Canadian Cardiovascular Society (CCS)
Measured: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Rate of complete revascularization
To evaluate and compare the rate of complete revascularization in each of the two strategies. Complete revascularization is defined as targeting arteries larger than 1.5 mm, with stenosis greater than 70%, and a good distal bed
Measured: Assessed at the end of the surgical procedure, evaluated within the intraoperative period, with an estimated duration of up to 600 minutes
Evolution of frailty status
Frailty status will be assessed based on the Fried Frailty Criteria, which includes five components: unintentional weight loss, exhaustion, weakness (grip strength), slowness (gait speed), and low physical activity. Patients will be categorized as robust (0 criteria), pre-frail (1-2 criteria), or frail (3-5 criteria) at baseline and at follow-up. Changes in frailty status over time will be evaluated to determine progression, stability, or improvement
Measured: From the date of hospital discharge until 6 months postoperatively and from the date of hospital discharge until 12 months postoperatively, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 201931 Dec 2025

First posted15 Jan 2015 (estimated)
Study start1 Jan 2019
Primary completion31 Dec 2024
Study completion31 Dec 2025 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Frail ElderlyStudies of the same condition, open and under way.
More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Eligible patients will be randomly assigned to off-pump CABG or on-pump CABG procedure.
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 440 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02338947
Sponsor's protocol ID: USaoPauloGH1000
Other IDs: Sao Paulo Research Foundation
Acronym: FRAGILE
Status last verified: Jan 2025
First submitted: 29 Aug 2014
Last updated: 5 Mar 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Mejia OAV, Sa MPBO, Deininger MO, Dallan LRP, Segalote RC, Oliveira MAP, Atik FA, Santos MAD, Silva PGMBE, Milani RM, Hueb AC, Monteiro R, Lima RC, Lisboa LAF, Dallan LAO, Puskas J, Jatene FB. Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study Protocol for the FRAGILE Multicenter Randomized Controlled Trial. Braz J Cardiovasc Surg. 2017 Sep-Oct;32(5):428-434. doi: 10.21470/1678-9741-2017-0196.
PubMed 29211225

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Prospective, Randomized, Clinical Trial Comparing Off-pump Versus On-pump Coronary Artery Bypass Grafting in Frail Patients
ClinicalTrials.gov ID: NCT02338947
Acronym / sponsor ID: FRAGILE / USaoPauloGH1000
Conditions: Frail Elderly, Coronary Artery Disease
Keywords: Frail elderly, Coronary artery bypass surgery, Off-pump, On-pump, Randomized controlled trial
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 440 participants (actual)
Lead sponsor: University of Sao Paulo General HospitalUniversity, hospital or other
Collaborators: Beneficência Portuguesa de São Paulo, Instituto Nacional de Cardiologia de Laranjeiras, Clinical Hospital Samuel Libânio of Pouso Alegre, Hospital do Coração de Messejana Dr. Carlos Alberto Studart
Study start: 1 Jan 2019 (actual)
Primary completion: 31 Dec 2024 (actual)
Study completion: 31 Dec 2025 (estimated)
First posted: 15 Jan 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2
Model description: Eligible patients will be randomly assigned to off-pump CABG or on-pump CABG procedure.

Arm	Type	Receives
Off-pump coronary-artery bypass grafting - OPCAB	Active comparator	Other: Off-pump coronary-artery bypass graftingPre-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.
On-pump coronary-artery bypass grafting - CABG	Active comparator	Other: On-pump coronary-artery bypass graftingPre-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.

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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.

Key exclusion criteria (1 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Off-pump coronary-artery bypass graftingAlso: OPCABSurgical 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.	Other	Off-pump coronary-artery bypass grafting - OPCAB
On-pump coronary-artery bypass graftingAlso: CABGSurgical 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.	Other	On-pump coronary-artery bypass grafting - CABG

Primary outcome

Major adverse cardiac and cerebrovascular events after OPCAB and CABG in pre-frail and frail patients
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
This composite outcome comprises: all cause death, acute myocardial infarction, stroke, renal failure, acute respiratory distress syndrome and bleeding reoperation

13 secondary outcomes

Operative time
Time frame: From the start of anesthesia induction to the end of the surgical procedure
Mechanical ventilation time
Time frame: From the initiation of mechanical ventilation in the operating room or ICU to the time of successful extubation
Hyperdynamic shock
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
New onset of atrial fibrillation
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Need for pacing >24 hours
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Renal replacement therapy
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Pneumonia
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Length of stay in intensive care unit
Time frame: From the date of surgery until ICU discharge, assessed up to 30 days
Length of stay in hospital
Time frame: From the date of surgery until hospital discharge, assessed up to 90 days
Transfusion requirement
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Recurrence of angina
Time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days
Rate of complete revascularization
Time frame: Assessed at the end of the surgical procedure, evaluated within the intraoperative period, with an estimated duration of up to 600 minutes
Evolution of frailty status
Time frame: From the date of hospital discharge until 6 months postoperatively and from the date of hospital discharge until 12 months postoperatively, assessed up to 1 year

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
Derived from this study: PubMed 29211225Mejia OAV, Sa MPBO, Deininger MO, Dallan LRP, Segalote RC, Oliveira MAP, Atik FA, Santos MAD, Silva PGMBE, Milani RM, Hueb AC, Monteiro R, Lima RC, Lisboa LAF, Dallan LAO, Puskas J, Jatene FB. Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study Protocol for the FRAGILE Multicenter Randomized Controlled Trial. Braz J Cardiovasc Surg. 2017 Sep-Oct;32(5):428-434. doi: 10.21470/1678-9741-2017-0196.
São Paulo Research FoundationLink provided by the sponsor.
Zerbini FoundationLink provided by the sponsor.
Brazilian Cardiovascular SocietyLink provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Omar AV Mejia, MD, PhD study director

InCor Heart Institute

Fábio B Jatene, MD, PhD study chair

InCor Heart Institute

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Brazil, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major adverse cardiac and cerebrovascular events after OPCAB and CABG in pre-frail and frail patients (time frame: From the date of surgery until 30 days postoperatively, assessed up to 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02338947, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2025.