Volatile Anesthetics to Reduce Mortality in Cardiac Surgery

NCT ID: NCT02105610

Last Updated: 2019-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-14
• Study Completion Date: 2018-09-30

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).

Conditions

Aortocoronary Bypass; Cardiac Surgery; Coronary Artery Bypass Grafting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

volatile anesthetics (desflurane, isoflurane, sevoflurane)

Group Type: EXPERIMENTAL

desflurane, isoflurane, sevoflurane

Intervention Type: DRUG

total intravenous anesthesia

Group Type: ACTIVE_COMPARATOR

total intravenous anesthetics

Intervention Type: DRUG

Interventions

desflurane, isoflurane, sevoflurane

Intervention Type: DRUG

total intravenous anesthetics

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università Vita-Salute San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Landoni

MD, Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

alberto zangrillo, Prof

Role: STUDY_CHAIR

Vita-Salute University of Milano

Locations

Mohammed Bin Khalifa Bin Sulman Al-Khalifa Cardiac Center - Bahrain

Bahrein, , Bahrain

Hospital das Clínicas da Faculdade de Medicina da USP - Istituto do Coracao

São Paulo, Barazil, Brazil

Dante Pazzanese Institute of Cardiology

São Paulo, , Brazil

Heart Center Pontica

Burgas, , Bulgaria

Beijing Anzhen Hospital, Capital Medical University

Beijing, , China

The Second Xiangya Hospital of Central South University

Changsha, , China

Wuhan Asia Heart Hospital

Hubei, , China

1st Affiliated Hospital of Fourth Military University

Xi'an, , China

University Hospital Dubrava

Dubrava, , Croatia

General University Hospital, Charles University

Prague, Czech Republic, Czechia

Institute for Clinical and Experimental Medicine

Prague, Czech Republic, Czechia

Mansoura University hospitals

Egypt, Egypt, Egypt

Faculty of Medicine - Zagazig University

Zagazig, , Egypt

Policlinico San Orsola-Malpighi

Bologna, , Italy

Spedali Civili

Brescia, , Italy

Policlinico Universitario Magna Graecia

Catanzaro, , Italy

Ospedale San Raffaele di Milano, Italy

Milan, , Italy

Humanitas

Milan, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Azienda Ospedaliera San Camillo-Forlanini

Roma, , Italy

Policlinico Universitario Campus Biomedico

Roma, , Italy

AOU Città della Salute e della Scienza

Torino, , Italy

Hospital Pulau Pinang

George Town, Malaysia, Malaysia

Hospital Serdang

Lumpur, Malaysia, Malaysia

University Malaya Medical Centre

Lumpur, Malaysia, Malaysia

Sarawak General Hospital

Sarawak, Malaysia, Malaysia

Hospital Santa Maria

Lisbon, , Portugal

Federal Centre for Cardiac Surgery

Astrakhan, , Russia

Scientific Research Institute for Complex Issues of Cardiovascular Disease

Kemerovo, , Russia

Moscow Clinical Regional Research Institute

Moscow, , Russia

Negovskiy Reanimatology Research Institute

Moscow, , Russia

State Research Institute of Circulation Pathology

Novosibirsk, , Russia

Federal Almazov Medical Research Centre

Saint Petersburg, , Russia

Ural Institute of Cardiology

Yekaterinburg, , Russia

King Abdullah Medical City - KAMC

Mecca, , Saudi Arabia

Institute of Cardiovascular Diseases "Dedinje"

Belgrade, , Serbia

Countries

Bahrain; Brazil; Bulgaria; China; Croatia; Czechia; Egypt; Italy; Malaysia; Portugal; Russia; Saudi Arabia; Serbia

References

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.

Reference Type: BACKGROUND

PMID: 23852263 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22726656 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28533194 (View on PubMed)

Lomivorotov V, Ruzankin PS, Lembo R, Tarasenko AS, Chernyavskiy A, Crivellari M, Monaco F, Ruggeri L, Pieri M, Lomivorotova L, Belletti A. Volatile versus Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery: Analysis of 1586 MYRIAD Trial Patients Managed with the Same Perioperative Protocol. Rev Cardiovasc Med. 2022 Jul 21;23(8):265. doi: 10.31083/j.rcm2308265. eCollection 2022 Aug.

Reference Type: DERIVED

PMID: 39076624 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30888743 (View on PubMed)

Other Identifiers

VOLATILE/38/OSR

Identifier Type: -

Identifier Source: org_study_id