Multivessel Minimally Invasive Coronary Bypass Grafting as HYBRID Revascularization Versus Conventional Off-pump Coronary Artery Bypass Grafting

Official title

MICRA-HYBRID Trial: A Randomized Controlled Trial of 'Multivessel Minimally Invasive Coronary Bypass Grafting as HYBRID Revascularization Versus Conventional Off-Pump Coronary Artery Bypass Grafting'

Overview

The MICRA-HYBRID trial is a prospective, multicenter, randomized controlled study comparing multivessel hybrid coronary revascularization (HCR) as minimally invasive arterial bypass grafting to left-sided coronary targets (LAD and LCx) plus PCI of the RCA versus conventional off-pump coronary artery bypass grafting (OPCAB) via median sternotomy in patients with three-vessel coronary artery disease. The primary goal is to evaluate whether multivessel-HCR provides superior 30-day "textbook" clinical outcomes (mortality, MI, stroke, re-exploration for bleeding, and other complications) while improving perioperative recovery and long-term cardiovascular outcomes.

Detailed description

Coronary artery disease remains the leading cause of cardiovascular mortality worldwide. For complex, multivessel disease, surgical revascularization via CABG or OPCAB remains the guideline-recommended standard due to superior long-term outcomes compared with PCI alone. However, traditional sternotomy CABG/OPCAB is associated with significant surgical trauma, prolonged recovery, and elevated perioperative morbidity.

Minimally invasive coronary surgery (MICS) with off-pump arterial grafting through a small thoracotomy has shown favorable short-term recovery and lower morbidity in both single and multivessel disease cases. Traditionally, MICS has been limited to grafting the left anterior descending artery (LAD), with other coronary lesions treated by PCI, known as hybrid coronary revascularization (HCR). While most studies have focused on single-vessel HCR (typically LAD), the potential long-term benefits of including the circumflex (Cx) artery in a multivessel-HCR strategy remain unexplored. Given that three-vessel CAD is the most common indication for CABG, evaluating a multivessel-HCR approach (LAD + Cx via MICS, RCA via PCI) is essential.

The MICRA-HYBRID trial will randomize 250 patients with three-vessel coronary disease eligible for complete revascularization to either multivessel-HCR or conventional total-arterial OPCAB (median sternotomy, anaortic, off-pump). The primary efficacy endpoint is a composite "Textbook Outcome" at 30 days, defined by absence of death, MI, stroke, re-exploration for bleeding, and other major complications. Secondary endpoints include individual components of the Textbook Outcome, perioperative recovery parameters (ICU/hospital length of stay, ventilator time, transfusion requirement), health-related quality of life (EQ-5D), pulmonary recovery metrics, angina class (CCS), and long-term outcomes including MACCE and target-vessel revascularization up to five years.

Interventions

• Procedure Multivessel Hybrid Coronary Revascularization
  Multivessel-HCR consists of MICS revascularization of the left sided coronary vessels (LAD , Cx) combined with PCI for the RCA during the same admission or within 4 weeks postoperatively. Surgical revascularization is performed through MICS which consists of either robotically or non-robotically assisted thoracoscopic IMA harvesting followed by total arterial off-pump anastomosis of the grafts through a left anterior 3-5 cm mini-thoracotomy. PCI will be performed via radial or femoral access acc
• Procedure Off-pump coronary arterial bypass grafting (OPCAB)
  OPCAB will be performed as per clinical routine at each center through a median sternotomy. IMA harvesting (pedicled or skeletonised) follows each center's routine. An anaortic, total arterial strategy with a LIMA-LAD graft and complete revascularisation is obliged.

Primary outcome measures

• Composite Absence of Adverse Events within 30 Days Postoperatively (Textbook Outcome) [Time frame: 30 days postoperatively]

Secondary outcome measures (12)

• Conversion to Sternotomy [Time frame: Peri-operatively]
• Conversion to Cardiopulmonary Bypass [Time frame: Peri-operatively]
• Intensive Care Unit (ICU) Stay [Time frame: 30 days postoperatively]
• Postoperative Hospital Stay [Time frame: 30 days postoperatively]
• Mechanical Ventilation Time [Time frame: 30 days postoperatively]
• Postoperative Blood Loss [Time frame: 30 days postoperatively]
• Transfusion Requirement [Time frame: 30 days postoperatively]
• Phrenic Nerve Injury [Time frame: 30 days postoperatively]
• Postoperative Peak Expiratory Flow (PEF) [Time frame: 30 days postoperatively]
• Quality of Life Assessment (EQ-5D) [Time frame: 1 year]
• Angina Assessment (CCS Classification) [Time frame: 1 year]
• Short-term Healthcare Costs [Time frame: 30 days]

Eligibility criteria

Inclusion criteria

• Patients with three-vessel disease (either angiographic stenoses >70% or a fractional flow reserve value ≤0.80)
• Left main diameter stenosis ≥50% or a left main intravascular ultrasound minimal luminal area of ≤4.5 mm2 or fractional flow reserve value ≤0.80 combined with significant CAD of the right coronary artery

Exclusion criteria

A potential participant who meets any of the following criteria will be excluded from participation in this study:

• Age < 18 or > 85 years
• Chronic total occlusion of the RCA
• In-stent RCA restenosis
• RCA stenosis with high-risk clinical features requiring urgent PCI or surgical revasculari-zation.
• Reverse hybrid coronary revascularization, defined as PCI-RCA followed by surgical re-vascularization.
• Acute cardiac ischemia necessitating immediate intervention.
• EF < 30 %
• eGFR < 30 ml/min
• Indication for concomitant cardiac surgery (e.g. valve or arrhythmia surgery) or non-cardiac surgery
• Previous thoracic or cardiac surgery, mediastinal irradiation, significant trauma to the chest
• Preoperative severe end-organ dysfunction (dialysis, liver failure, respiratory failure) or cancer.
• Hemodynamically significant left subclavian stenosis
• Severe chest wall deformities
• History of pericarditis
• Body mass index > 40 Kg/m2.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Belgium · 1 center

• University Hospitals Leuven — Leuven

Netherlands · 1 center

• Catharina Hospital Eindhoven — Eindhoven

Publications

• van Steenbergen GJ, Schulz DN, Slingerland SR, Tonino PA, Soliman-Hamad MA, Dekker L, van Veghel D. Introduction of a New Method to Monitor Patient-Relevant Outcomes and Costs: Using a Quality Improvement Project in Transcatheter Aortic Valve Implantation Care as an Example. Qual Manag Health Care. 2023 Oct-Dec 01;32(4):247-256. doi: 10.1097/QMH.0000000000000401. Epub 2023 Mar 16. PMID 36940366
• Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction; Authors/Task Force Members Chairpersons; Thygesen K, Alpert JS, White HD; Biomarker Subcommittee; Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA; ECG Subcommittee; Chaitman BR, Clemmensen PM, Johanson P, Hod H; Imaging Subcommittee; Underwood PMID 22958960
• Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 PMID 30153967
• Modrau IS, Nielsen PH, Nielsen DV, Christiansen EH, Hoffmann T, Parner ET, Benhassen LL. Outcome of hybrid compared to conventional revascularization in multivessel coronary artery disease. Scand Cardiovasc J. 2020 Dec;54(6):376-382. doi: 10.1080/14017431.2020.1821910. Epub 2020 Sep 30. PMID 32998590
• Halkos ME, Ford L, Peterson D, Bluestein SM, Liberman HA, Kilgo P, Puskas JD, Guyton RA, Chowdhury R. The impact of hybrid coronary revascularization on hospital costs and reimbursements. Ann Thorac Surg. 2014 May;97(5):1610-5; discussion 1615-6. doi: 10.1016/j.athoracsur.2014.01.047. Epub 2014 Mar 15. PMID 24636706
• Gianoli M, de Jong AR, van der Harst P, van der Kaaij NP, Jacob KA, Suyker WJL. Cost Analysis of Robot-Assisted Versus On-Pump and Off-Pump Coronary Artery Bypass Grafting: A Single-Center Surgical and 30-Day Outcomes Comparison. Innovations (Phila). 2024 Jul-Aug;19(4):416-424. doi: 10.1177/15569845241269312. Epub 2024 Sep 12. PMID 39267423
• Michael Porter, Thomas Lee. The Strategy That Will Fix Healthcare. The Magazine.
• Zhang S, Li P, Li G, Yan Y, Sun T, Lin J, Zhang C, Liu S, Qu Z, You B. Generalized hybrid coronary revascularization vs. conventional off-pump coronary artery bypass grafting for multivessel coronary artery disease. Front Cardiovasc Med. 2025 Feb 21;12:1459072. doi: 10.3389/fcvm.2025.1459072. eCollection 2025. PMID 40060966

Identifiers

NCT: NCT07314138 · NL-010448

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗