Clinical trial NCT05487612: MiECC Versus Conventional Cardiopulmonary Bypass in Cardiac Surgery (MiECS)
Official title: Minimally Invasive Extracorporeal Circulation Versus Conventional Cardiopulmonary Bypass in Patients Undergoing Cardiac Surgery (MiECS): a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Aortic Valve Stenosis
Extracorporeal Circulation; Complications
Keywords: Cardiopulmonary bypass
Extracorporeal circulation
Minimal invasive extracorporeal circulation
Coronary artery bypass grafting
Aortic valve replacement
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
Collaborators: name: Minimal Invasive Extracorporeal Technologies International Society (MiECTiS)
First posted: 2022-08-04
Enrollment: 1300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients undergoing elective or urgent coronary artery bypass grafting, aortic valve replacement or both procedures CABG+AVR using extracorporeal circulation without circulatory arrest will be randomised (1:1 ratio) to having surgery using Minimal Invasive Extracorporeal Circulation (MiECC) or conventional cardiopulmonary bypass (cCPB).
Primary purpose: TREATMENT

Brief summary: MiECS is one of the largest multicentre randomised controlled trials on extracorporeal circulation conducted under the auspices of Minimal Invasive Extracorporeal Technologies International Society (MiECTiS). It is designed to ultimately address the emerging effectiveness of MiECC systems in the light of modern perfusion practice worldwide. The primary hypothesis is that MiECC, as compared to conventional CPB (cCPB), reduces the proportion of patients experiencing serious perfusion-related postoperative morbidity after cardiac surgery. The study will be led by the Clinical Research Unit of the Special Unit for Biomedical Research and Education (SUBRE), Aristotle University of Thessaloniki School of Medicine in Greece (AUSoM) with Chief Investigator Professor Kyriakos Anastasiadis, who is a key-opinion-leader in the field of MiECC, founder and Executive Board of MiECTiS.

Detailed description: Despite a fall in mortality rates over the past decade, patients having cardiac surgery continue to experience serious postoperative complications. The risk of serious and relatively common surgical complications is often a consequence of stopping the heart during the operation, using the heart and lung machine (conventional cardiopulmonary bypass; cCPB), and restarting and reperfusing the heart at the end of the operation. Although several strategies have been developed to reduce such complications, they still occur and can be life threatening; they also increase the length of time a patient spends in the hospital.

Miniaturised heart lung machines (minimally invasive extracorporeal circulation; MiECC) have been developed with the aim of reducing the number of postoperative complications arising from using cCPB. Because of the variety of miniaturised systems that have been evaluated, the different types of patients and outcomes investigated, and the poor quality of previous studies, the effectiveness of MiECC in reducing postoperative complications has not been established and most hospitals continue to use cCPB.

Our primary hypothesis is that, compared to cCPB, using a MiECC system during cardiac surgery reduces the proportion of patients having one of several serious postoperative complications (death, myocardial infarction, stroke, acute kidney injury, reintubation, tracheostomy, mechanical ventilation for more than 48 hours, or reoperation) up to 30 days after surgery. In addition, the investigators hypothesise that MiECC reduces the amount of blood products transfused, time to discharge from the cardiac intensive care unit and hospital and the health care resources used during the hospital stay.

Study investigators propose to carry out a large, multicentre randomised controlled trial in 10 to 15 cardiac surgery centres worldwide. Patients will be eligible if they are having coronary artery bypass surgery, aortic valve replace or both using a heart lung machine without circulatory arrest. Centres may recruit patients having all, or a subset of, operation types.

It is expected that 20 % to 23% of patients will experience one or more of the serious complications (the primary outcome). In order to be able confidently to detect a 30% relative reduction in the risk of this outcome, the investigators plan to recruit 1,300 participants across all sites.

Eligibility criteria: Inclusion Criteria:

* All patients undergoing any elective or urgent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or CABG+AVR surgery using extracorporeal circulation without circulatory arrest.

Exclusion Criteria:

* Requirement for emergency or salvage operation.
* Requirement for major aortic surgery (e.g. aortic root replacement).
* Contraindication or objection (e.g. Jehovah's Witnesses) to transfusion of blood products.
* Congenital or acquired platelet, red cell or clotting disorders (patients with iron deficient anaemia will not be excluded).
* Inability to give informed consent for the study (e.g. learning or language difficulties).

Primary outcomes:
measure: Composite outcome of postoperative serious adverse events
timeFrame: 30 days after randomization following the index admission
Secondary outcomes:
measure: All-cause mortality
timeFrame: 30 days after randomization following the index admission
measure: New-onset postoperative atrial fibrillation
timeFrame: Through initial hospital admission from surgery to initial discharge from hospital, an average of 1 week.
measure: Rate of red blood cells transfusion
timeFrame: 30 days after randomization following the index admission
measure: Rate of platelet transfusion
timeFrame: 30 days after randomization following the index admission
measure: Rate of fresh frozen plasma transfusion
timeFrame: 30 days after randomization following the index admission
measure: Rate of cryoprecipitate transfusion
timeFrame: 30 days after randomization following the index admission
measure: Activated Factor VII administration
timeFrame: 30 days after randomization following the index admission
measure: Fibrinogen administration
timeFrame: 30 days after randomization following the index admission
measure: Prothrombin complex concentrate administration
timeFrame: 30 days after randomization following the index admission
measure: Time to discharge from cardiac ICU
timeFrame: Through initial hospital admission from surgery to initial discharge from hospital, an average of 1 week.
measure: Time to discharge from hospital
timeFrame: Through initial hospital admission from surgery to initial discharge from hospital, an average of 1 week.
measure: Delirium
timeFrame: Up to 5 days postoperatively
measure: Health-Related Quality of Life (HRQoL)
timeFrame: 90 days after randomization
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Perfusion Services University Health Network, Toronto General Hospital
city: Coswig
country: Germany
facility: Department of Cardiac Surgery
city: Göttingen
country: Germany
facility: Department of Thoracic and Cardiovascular Surgery, University Medical Centre Goettingen
city: Ulm
country: Germany
facility: Department of Cardiothoracic and Vascular Surgery, Ulm University Hospital
city: Thessaloníki
country: Greece
facility: Cardiothoracic Department AHEPA University Hospital
city: Bari
country: Italy
facility: Department of Cardiac Surgery GVM Anthea Hospital
city: Palermo
country: Italy
facility: Department of Cardiac Surgery GVM Maria Eleonora Hospital
city: Ankara
country: Turkey
facility: Department of Cardiovascular Surgery, Ankara City Hospital
city: Izmir
country: Turkey
facility: Department of Cardiovascular Surgery, Izmir Bakırçay University, Faculty of Medicine
city: Cambridge
country: United Kingdom
facility: Department of Cardiac Surgery, Royal Papworth Hospital
city: Hull
country: United Kingdom
facility: Deparment of Cardiac Surgery, Castle Hill Hospital
city: London
country: United Kingdom
facility: Department of Cardiothoracic Surgery, Hammersmith Hospital
Study officials:
affiliation: Aristotle University Of Thessaloniki
name: Kyriakos Anastasiadis, Professor
role: STUDY_CHAIR
affiliation: Aristotle University Of Thessaloniki
name: Polychronis Antonitsis, Assoc. Prof.
role: STUDY_DIRECTOR
References:
citation: Anastasiadis K, Murkin J, Antonitsis P, Bauer A, Ranucci M, Gygax E, Schaarschmidt J, Fromes Y, Philipp A, Eberle B, Punjabi P, Argiriadou H, Kadner A, Jenni H, Albrecht G, van Boven W, Liebold A, de Somer F, Hausmann H, Deliopoulos A, El-Essawi A, Mazzei V, Biancari F, Fernandez A, Weerwind P, Puehler T, Serrick C, Waanders F, Gunaydin S, Ohri S, Gummert J, Angelini G, Falk V, Carrel T. Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS). Interact Cardiovasc Thorac Surg. 2016 May;22(5):647-62. doi: 10.1093/icvts/ivv380. Epub 2016 Jan 26.
citation: Anastasiadis K, Antonitsis P, Asteriou C, Deliopoulos A, Argiriadou H. Modular minimally invasive extracorporeal circulation ensures perfusion safety and technical feasibility in cardiac surgery; a systematic review of the literature. Perfusion. 2022 Nov;37(8):852-862. doi: 10.1177/02676591211026514. Epub 2021 Jun 17.
citation: COMICS investigators, The COMICS investigators. Conventional versus minimally invasive extracorporeal circulation in patients undergoing cardiac surgery: protocol for a randomised controlled trial (COMICS). Perfusion. 2021 May;36(4):388-394. doi: 10.1177/0267659120946731. Epub 2020 Aug 12.
citation: Wahba A, Milojevic M, Boer C, De Somer FMJJ, Gudbjartsson T, van den Goor J, Jones TJ, Lomivorotov V, Merkle F, Ranucci M, Kunst G, Puis L; EACTS/EACTA/EBCP Committee Reviewers. 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery. Eur J Cardiothorac Surg. 2020 Feb 1;57(2):210-251. doi: 10.1093/ejcts/ezz267. No abstract available.
citation: Ranucci M, Johnson I, Willcox T, Baker RA, Boer C, Baumann A, Justison GA, de Somer F, Exton P, Agarwal S, Parke R, Newland RF, Haumann RG, Buchwald D, Weitzel N, Venkateswaran R, Ambrogi F, Pistuddi V. Goal-directed perfusion to reduce acute kidney injury: A randomized trial. J Thorac Cardiovasc Surg. 2018 Nov;156(5):1918-1927.e2. doi: 10.1016/j.jtcvs.2018.04.045. Epub 2018 Apr 18.
citation: Anastasiadis K, Argiriadou H, Deliopoulos A, Antonitsis P. Minimal invasive extracorporeal circulation (MiECC): the state-of-the-art in perfusion. J Thorac Dis. 2019 Jun;11(Suppl 10):S1507-S1514. doi: 10.21037/jtd.2019.01.66. No abstract available.
citation: Kowalewski M, Pawliszak W, Raffa GM, Malvindi PG, Kowalkowska ME, Zaborowska K, Kowalewski J, Tarelli G, Taggart DP, Anisimowicz L. Safety and efficacy of miniaturized extracorporeal circulation when compared with off-pump and conventional coronary artery bypass grafting: evidence synthesis from a comprehensive Bayesian-framework network meta-analysis of 134 randomized controlled trials involving 22 778 patients. Eur J Cardiothorac Surg. 2016 May;49(5):1428-40. doi: 10.1093/ejcts/ezv387. Epub 2015 Nov 3.
citation: Anastasiadis K, Antonitsis P, Papazisis G, Haidich B, Liebold A, Punjabi P, Gunaydin S, El-Essawi A, Rao V, Serrick C, Condello I, Nasso G, Bozok S, Daylan A, Argiriadou H, Deliopoulos A, Karapanagiotidis G, Ashkanani F, Moorjani N, Cale A, Erdoes G, Bennett M, Starinieri P, Carrel T, Murkin J. Minimally invasive extracorporeal circulation versus conventional cardiopulmonary bypass in patients undergoing cardiac surgery (MiECS): Rationale and design of a multicentre randomised trial. Perfusion. 2025 May;40(4):923-932. doi: 10.1177/02676591241272009. Epub 2024 Aug 1.