Aortocoronary BypassPhase 4MYRIADNCT02105610
Volatile Anesthetics to Reduce Mortality in Cardiac Surgery
A Phase 4 study testing desflurane, isoflurane, sevoflurane and total intravenous anesthetics in people with Aortocoronary Bypass and Cardiac Surgery, run by Università Vita-Salute San Raffaele at 36 sites in 13 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortocoronary Bypass, Cardiac Surgery, Coronary Artery Bypass Grafting
- What is being tested?
- desflurane, isoflurane, sevoflurane and total intravenous anesthetics
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,400 participants
- Where
- 36 sitesin 13 countries
- Study dates
- 14 Apr 2014to Sep 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
36 sites in 13 countries.
36 sites in 13 countries
Italy9 sites
Policlinico San Orsola-Malpighi
Bologna
Spedali Civili
Brescia
Policlinico Universitario Magna Graecia
Catanzaro
Ospedale San Raffaele di Milano, Italy
Milan, 20132
Humanitas
Milan
Azienda Ospedaliera di Padova
Padova
Azienda Ospedaliera San Camillo-Forlanini
Roma
Policlinico Universitario Campus Biomedico
Roma
AOU Città della Salute e della Scienza
Torino
Russia7 sites
Federal Centre for Cardiac Surgery
Astrakhan
Scientific Research Institute for Complex Issues of Cardiovascular Disease
Kemerovo
Moscow Clinical Regional Research Institute
Moscow
Negovskiy Reanimatology Research Institute
Moscow
State Research Institute of Circulation Pathology
Novosibirsk
Federal Almazov Medical Research Centre
Saint Petersburg
Ural Institute of Cardiology
Yekaterinburg
China4 sites
Beijing Anzhen Hospital, Capital Medical University
Beijing
The Second Xiangya Hospital of Central South University
Changsha
Wuhan Asia Heart Hospital
Hubei
1st Affiliated Hospital of Fourth Military University
Xi'an
Malaysia4 sites
Hospital Pulau Pinang
George Town, Malaysia
Hospital Serdang
Lumpur, Malaysia
University Malaya Medical Centre
Lumpur, Malaysia
Sarawak General Hospital
Sarawak, Malaysia
Brazil2 sites
Hospital das Clínicas da Faculdade de Medicina da USP - Istituto do Coracao
São Paulo, Barazil
Dante Pazzanese Institute of Cardiology
São Paulo
Czechia2 sites
General University Hospital, Charles University
Prague, Czech Republic
Institute for Clinical and Experimental Medicine
Prague, Czech Republic
Egypt2 sites
Mansoura University hospitals
Egypt, Egypt
Faculty of Medicine - Zagazig University
Zagazig
Bahrain1 site
Mohammed Bin Khalifa Bin Sulman Al-Khalifa Cardiac Center - Bahrain
Bahrein
About this study
Official title: Volatile Anesthetics to Reduce Mortality in Cardiac Surgery: A Multicentre Randomized Controlled Study
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).
Read more
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).
- Being tested
- desflurane, isoflurane, sevoflurane, total intravenous anesthetics
- Keywords
- volatile anesthetics, desflurane, isoflurane, sevoflurane, TIVA, cardiac surgery, mortality, anesthesia, intensive care
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
desflurane, isoflurane, sevofluraneDrug
total intravenous anestheticsDrug
| Study group | Role | What they receive |
|---|---|---|
| volatile anesthetics (desflurane, isoflurane, sevoflurane) | Experimental | Not described Receives: Drug: desflurane, isoflurane, sevoflurane |
| total intravenous anesthesia | Active comparator | Not described Receives: Drug: total intravenous anesthetics |
What is being measured
The primary outcome is the main question the study is designed to answer.
mortality
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study start14 Apr 2014
- Primary completionOct 2017
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Aortocoronary BypassStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5,400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
- Investigators
- alberto zangrillo, Prof, Study chair, Vita-Salute University of Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02105610
- Sponsor's protocol ID
- VOLATILE/38/OSR
- Acronym
- MYRIAD
- Status last verified
- Mar 2019
- First submitted
- 2 Apr 2014
- Last updated
- 2 Apr 2019
- Results posted
- No
Publications
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.
PubMed 23852263Landoni 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.
PubMed 22726656Landoni 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.
PubMed 28533194Lomivorotov 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.
PubMed 39076624Landoni 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.
PubMed 30888743
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Volatile Anesthetics to Reduce Mortality in Cardiac Surgery: A Multicentre Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT02105610
- Acronym / sponsor ID
- MYRIAD / VOLATILE/38/OSR
- Keywords
- volatile anesthetics, desflurane, isoflurane, sevoflurane, TIVA, cardiac surgery, mortality, anesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,400 participants (actual)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Study start
- 14 Apr 2014 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 7 Apr 2014 (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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| volatile anesthetics (desflurane, isoflurane, sevoflurane) | Experimental | Drug: desflurane, isoflurane, sevoflurane |
| total intravenous anesthesia | Active comparator | Drug: total intravenous anesthetics |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| desflurane, isoflurane, sevoflurane | Drug | volatile anesthetics (desflurane, isoflurane, sevoflurane) |
| total intravenous anesthetics | Drug | total intravenous anesthesia |
Primary outcome
mortality
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2019.
- Background: PubMed 23852263Landoni 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.
- Background: PubMed 22726656Landoni 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.
- Background: PubMed 28533194Landoni 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.
- Derived from this study: PubMed 39076624Lomivorotov 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.
- Derived from this study: PubMed 30888743Landoni 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.
Related trials for Aortocoronary Bypass
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
RecruitingEarly Phase 1
Thiamine Intervention and Coronary Artery Bypass Grafting
Coronary Heart Disease, Coronary Artery Bypass Grafting
Not yet recruitingObservational study
Preoperative Gastric Ultrasound and Anaesthetic Management in Patients Undergoing Coronary Artery Bypass Grafting
Preoperative Fasting, Pulmonary Aspiration During Anesthetic Induction
Active, not recruiting
Investigation of the Effects of Respiratory Muscle Training Combined With Otago Exercises in Elderly Patients Undergoing Coronary Artery Bypass Graft Surgery
Coronary Artery Bypass Graft (CABG)
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.
alberto zangrillo, Prof study chair
Vita-Salute University of Milano
36 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing desflurane, isoflurane, sevoflurane and total intravenous anesthetics in people with Aortocoronary Bypass and Cardiac Surgery, run by Università Vita-Salute San Raffaele at 36 sites in 13 countries.
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 4 inclusion and 12 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: finished, as of the sponsor's last update on 2 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in Italy, Russia, China, Malaysia, Brazil and 8 more countries. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
mortality (time frame: 1 year). 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 NCT02105610, which also lists 5 linked publications.
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 2 Apr 2019.