A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.
OBJECTIVE
Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes.


METHODS
Double-blind, placebo-controlled, multicenter randomized trial.


METHODS
Tertiary care hospitals.


METHODS
Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours.


RESULTS
The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction.


CONCLUSIONS
This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Anesthesia and Intensive Care, Policlinico Universitario "Magna Grecia," Catanzaro, Italy.
Alberto
A
Zangrillo
Cardiac Anesthesia and Intensive Care Unit, Monaldi Hospital A.O.R.N. "Dei Colli", Naples, Italy.
Gabriele
G
Alvaro
Department of Anaesthesia and Critical Care Medicine, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Antonio
A
Pisano
Department of Anaesthesia and Critical Care Medicine, Città della Salute e della Scienza, Torino, Italy.
Fabio
F
Guarracino
Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Dubrava, Zagreb, Croatia.
Rosetta
R
Lobreglio
Anesthesiology & Intensive Care Department Moscow Regional Clinical & Research Institute, Moscow, Russia.
Nikola
N
Bradic
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Rosalba
R
Lembo
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Stefano
S
Gianni
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Maria Grazia
MG
Calabrò
Department of Intensive Care, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia.
Valery
V
Likhvantsev
Anesthesia and Intensive Care, A.O.U. IRCSS IST San Martino, Genova, Italy.
Evgeny
E
Grigoryev
Cardiac Anesthesia and Intensive Care, Ospedale Civile SS. Annunziata, Sassari, Italy.
Giuseppe
G
Buscaglia
Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria Santa Maria della Misericordia, Udine, Italy.
Giovanni
G
Pala
Department of Cardiac Surgery, Ospedale S.Bortolo, Vicenza, Italy.
Elisabetta
E
Auci
Cardiac Anesthesia and Intensive Care Unit, Monaldi Hospital A.O.R.N. "Dei Colli", Naples, Italy.
Bruno
B
Amantea
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Fabrizio
F
Monaco
Cardiac Anesthesia and Intensive Care Unit, Monaldi Hospital A.O.R.N. "Dei Colli", Naples, Italy.
Giovanni
G
De Vuono
Department of Anesthesia and Critical Care, AORN "Dei Colli", Naples, Italy.
Antonio
A
Corcione
Department of Anaesthesia and Critical Care Medicine, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Nicola
N
Galdieri
Department of Anaesthesia and Critical Care Medicine, Città della Salute e della Scienza, Torino, Italy.
Claudia
C
Cariello
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Tiziana
T
Bove
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Evgeny
E
Fominskiy
Department of Cardiac Surgery, Ospedale S.Bortolo, Vicenza, Italy.
Stefano
S
Auriemma
Anesthesia and Intensive Care, S.Orsola-Malpighi University Hospital, Bologna, Italy.
Massimo
M
Baiocchi
Anesthesia and Intensive Care, Azienda Ospedaliera Ordine Mauriziano, Torino, Italy.
Alessandro
A
Bianchi
Anesthesia and Intensive Care, Azienda Ospedaliera Spedali Civili, Brescia, Italy.
Mario
M
Frontini
Departement of Cardiovascular Anaesthesia and Intensive Care, Azienda Ospedaliera S. Carlo, Potenza, Italy.
Gianluca
G
Paternoster
Anesthesia and Intensive Care, Ospedale S. Gerardo, Monza, Italy.
Fabio
F
Sangalli
Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Chew-Yin
CY
Wang
Anesthesia and Intensive Care, Azienda Ospedaliera Papardo-Piemonte, Messina, Italy.
Maria Chiara
MC
Zucchetti
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
Giuseppe
G
Biondi-Zoccai
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Marco
M
Gemma
Division of Cardiology, Medstar Washington Hospital Center, Washington DC.
Michael J
MJ
Lipinski
Department of Anesthesiology and Intensive Care, State Research Institute of Circulation Pathology, Novosibirsk, Russia.
Vladimir V
VV
Lomivorotov
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: landoni.giovanni@hsr.it.
Giovanni
G
Landoni
D058186:Acute Kidney Injury / Q000453:epidemiology; D002303:Cardiac Output, Low / Q000401:mortality / Q000628:therapy*; D006348:Cardiac Surgical Procedures / Q000401:mortality; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D007423:Intra-Aortic Balloon Pumping; D007902:Length of Stay / Q000706:statistics & numerical data; D011183:Postoperative Complications / Q000401:mortality / Q000628:therapy*; D011724:Pyridazines / Q000627:therapeutic use*; D012121:Respiration, Artificial; D000077464:Simendan
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan