Clinical trial NCT02105610: Volatile Anesthetics to Reduce Mortality in Cardiac Surgery
Official title: Volatile Anesthetics to Reduce Mortality in Cardiac Surgery: A Multicentre Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aortocoronary Bypass
Cardiac Surgery
Coronary Artery Bypass Grafting
Keywords: volatile anesthetics
desflurane
isoflurane
sevoflurane
TIVA
cardiac surgery
mortality
anesthesia
intensive care
Lead sponsor: Università Vita-Salute San Raffaele
Sponsor class: OTHER
First posted: 2014-04-07
Enrollment: 5400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is initial evidence that the choice of anesthesia can influence survival in the specific setting of coronary artery bypass grafting surgery (CABG).

A recent international consensus conference included volatile agents among the few drugs/techniques/strategies that might reduce perioperative mortality in cardiac surgery and that should be further studied. Volatile anesthetics (desflurane, isoflurane and sevoflurane) have non-anesthetic pharmacological characteristics that confer cardiac protection when compared to Total IntraVenous Anesthesia (TIVA). Several randomized controlled studies were summarized in a meta-analysis that documented a reduction in perioperative cardiac troponin release and mortality in patients receiving volatile anesthetics when compared to patients receiving a TIVA. There are four published studies (Bignami et al. 2009) (De Hert et al. 2009) (Jackobsen et al. 2007) (Landoni et al. 2007) suggesting that these benefits can translate into a reduced mortality rate in patients receiving volatile agents. The level of evidence for these four studies is not high (one meta-regression, one underpowered randomized controlled study, one retrospective study and one meta-analysis of small randomized studies) and there is need for a large multicentre randomized controlled study to confirm these findings, as suggested by the international consensus conference on this topic published in 2011 (Landoni et al 2011).

The purpose is to provide a large multicentre controlled randomized trial to demonstrate that volatile anesthetics can reduce 1 year mortality from 3% to 2% in patients undergoing CABG (either with or without cardiopulmonary bypass).

The results of this study can support the use of volatile agents in all CABG procedures worldwide (more than 500.000 per year) with 2.500 lives saved per year (in the hypothesis that nowadays half the procedures are performed with a TIVA and that 1 year mortality can be reduced from 3% to 2% using volatile agents).


Eligibility criteria: Inclusion Criteria:

* age \>18 years
* written informed consent
* scheduled procedures
* planned isolated CABG (multiple bypass are allowed; planned combined intervention such as CABG plus valve surgery are not allowed

Exclusion Criteria:

* pregnancy
* planned valve surgery or surgery on the aorta
* planned locoregional anesthesia without general anesthesia
* unstable or ongoing angina
* recent (\< 1 month) or ongoing acute myocardial infarction
* use of sulfonylurea, theophylline or allopurinol
* previous unusual response to an anesthetic agent
* inclusion in other randomised controlled studies in the previous 30 days
* any general anesthesia performed in the previous 30 days
* emergency operation (not scheduled)
* Kidney or liver transplant in medical history
* Liver cirrhosis (Child B or C)

Primary outcomes:
measure: mortality
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Bahrein
country: Bahrain
facility: Mohammed Bin Khalifa Bin Sulman Al-Khalifa Cardiac Center - Bahrain
city: Sao Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da USP - Istituto do Coracao
state: Barazil
city: Sao Paulo
country: Brazil
facility: Dante Pazzanese Institute of Cardiology
city: Burgas
country: Bulgaria
facility: Heart Center Pontica
city: Beijing
country: China
facility: Beijing Anzhen Hospital, Capital Medical University
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Hubei
country: China
facility: Wuhan Asia Heart Hospital
city: Xi'an
country: China
facility: 1st Affiliated Hospital of Fourth Military University
city: Dubrava
country: Croatia
facility: University Hospital Dubrava
city: Prague
country: Czechia
facility: General University Hospital, Charles University
state: Czech Republic
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
state: Czech Republic
city: Egypt
country: Egypt
facility: Mansoura University hospitals
city: Zagazig
country: Egypt
facility: Faculty of Medicine - Zagazig University
city: Bologna
country: Italy
facility: Policlinico San Orsola-Malpighi
city: Brescia
country: Italy
facility: Spedali Civili
city: Catanzaro
country: Italy
facility: Policlinico Universitario Magna Graecia
city: Milano
country: Italy
facility: Ospedale San Raffaele di Milano, Italy
city: Milano
country: Italy
facility: Humanitas
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo-Forlanini
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza
city: Lumpur
country: Malaysia
facility: Hospital Serdang
city: Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Penang
country: Malaysia
facility: Hospital Pulau Pinang
city: Sarawak
country: Malaysia
facility: Sarawak General Hospital
city: Lisbon
country: Portugal
facility: Hospital Santa Maria
city: Astrakhan
country: Russian Federation
facility: Federal Centre for Cardiac Surgery
city: Ekaterinburg
country: Russian Federation
facility: Ural Institute of Cardiology
city: Kemerovo
country: Russian Federation
facility: Scientific Research Institute for Complex Issues of Cardiovascular Disease
city: Moscow
country: Russian Federation
facility: Moscow Clinical Regional Research Institute
city: Moscow
country: Russian Federation
facility: Negovskiy Reanimatology Research Institute
city: Novosibirsk
country: Russian Federation
facility: State Research Institute of Circulation Pathology
city: Saint Petersburg
country: Russian Federation
facility: Federal Almazov Medical Research Centre
city: Mecca
country: Saudi Arabia
facility: King Abdullah Medical City - KAMC
city: Belgrade
country: Serbia
facility: Institute of Cardiovascular Diseases "Dedinje"
Study officials:
affiliation: Vita-Salute University of Milano
name: alberto zangrillo, Prof
role: STUDY_CHAIR
References:
citation: Landoni G, Greco T, Biondi-Zoccai G, Nigro Neto C, Febres D, Pintaudi M, Pasin L, Cabrini L, Finco G, Zangrillo A. Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery. Br J Anaesth. 2013 Dec;111(6):886-96. doi: 10.1093/bja/aet231. Epub 2013 Jul 12.
citation: Landoni G, Rodseth RN, Santini F, Ponschab M, Ruggeri L, Szekely A, Pasero D, Augoustides JG, Del Sarto PA, Krzych LJ, Corcione A, Slullitel A, Cabrini L, Le Manach Y, Almeida RM, Bignami E, Biondi-Zoccai G, Bove T, Caramelli F, Cariello C, Carpanese A, Clarizia L, Comis M, Conte M, Covello RD, De Santis V, Feltracco P, Giordano G, Pittarello D, Gottin L, Guarracino F, Morelli A, Musu M, Pala G, Pasin L, Pezzoli I, Paternoster G, Remedi R, Roasio A, Zucchetti M, Petrini F, Finco G, Ranieri M, Zangrillo A. Randomized evidence for reduction of perioperative mortality. J Cardiothorac Vasc Anesth. 2012 Oct;26(5):764-72. doi: 10.1053/j.jvca.2012.04.018. Epub 2012 Jun 20.
citation: Landoni G, Lomivorotov V, Pisano A, Nigro Neto C, Benedetto U, Biondi Zoccai G, Gemma M, Frassoni S, Agro FE, Baiocchi M, Barbosa Gomes Galas FR, Bautin A, Bradic N, Carollo C, Crescenzi G, Elnakera AM, El-Tahan MR, Fominskiy E, Farag AG, Gazivoda G, Gianni S, Grigoryev E, Guarracino F, Hanafi S, Huang W, Kunst G, Kunstyr J, Lei C, Lembo R, Li ZJ, Likhvantsev V, Lozovskiy A, Ma J, Monaco F, Navalesi P, Nazar B, Pasyuga V, Porteri E, Royse C, Ruggeri L, Riha H, Santos Silva F, Severi L, Shmyrev V, Uvaliev N, Wang CB, Wang CY, Winterton D, Yong CY, Yu J, Bellomo R, Zangrillo A. MortalitY in caRdIAc surgery (MYRIAD): A randomizeD controlled trial of volatile anesthetics. Rationale and design. Contemp Clin Trials. 2017 Aug;59:38-43. doi: 10.1016/j.cct.2017.05.011. Epub 2017 May 19.
citation: Landoni G, Lomivorotov VV, Nigro Neto C, Monaco F, Pasyuga VV, Bradic N, Lembo R, Gazivoda G, Likhvantsev VV, Lei C, Lozovskiy A, Di Tomasso N, Bukamal NAR, Silva FS, Bautin AE, Ma J, Crivellari M, Farag AMGA, Uvaliev NS, Carollo C, Pieri M, Kunstyr J, Wang CY, Belletti A, Hajjar LA, Grigoryev EV, Agro FE, Riha H, El-Tahan MR, Scandroglio AM, Elnakera AM, Baiocchi M, Navalesi P, Shmyrev VA, Severi L, Hegazy MA, Crescenzi G, Ponomarev DN, Brazzi L, Arnoni R, Tarasov DG, Jovic M, Calabro MG, Bove T, Bellomo R, Zangrillo A; MYRIAD Study Group. Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery. N Engl J Med. 2019 Mar 28;380(13):1214-1225. doi: 10.1056/NEJMoa1816476. Epub 2019 Mar 19.