A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design

Am Heart J. 2016 Jul:177:66-73. doi: 10.1016/j.ahj.2016.03.021. Epub 2016 Apr 23.

Abstract

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.

Design: Double-blind, placebo-controlled, multicenter randomized trial.

Setting: Tertiary care hospitals.

Interventions: 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.

Measurements and main 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Kidney Injury / epidemiology
  • Cardiac Output, Low / mortality
  • Cardiac Output, Low / therapy*
  • Cardiac Surgical Procedures / mortality
  • Cardiotonic Agents / therapeutic use*
  • Double-Blind Method
  • Humans
  • Hydrazones / therapeutic use*
  • Infusions, Intravenous
  • Intensive Care Units
  • Intra-Aortic Balloon Pumping*
  • Length of Stay / statistics & numerical data
  • Postoperative Complications / mortality
  • Postoperative Complications / therapy*
  • Pyridazines / therapeutic use*
  • Respiration, Artificial
  • Simendan

Substances

  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • Simendan