Rationale and design of the multicentre randomized trial investigating the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep study)

Eur J Heart Fail. 2010 Feb;12(2):186-92. doi: 10.1093/eurjhf/hfp189.

Abstract

Aims: Advanced chronic heart failure (CHF) is a clinical syndrome with high morbidity and mortality that often requires inotropic support for the alleviation of symptoms and congestion. There are no definite evidence-based data on the safety and efficacy of intermittent infusions of inotropic agents in this severe clinical condition. The purpose of the LevoRep study is to clarify whether pulsed infusions of the new inotropic agent levosimendan administered in an outpatient setting can safely improve exercise capacity, quality-of-life (QoL), and outcome in advanced CHF patients.

Methods: The LevoRep study is a prospective, randomized, double-blind, placebo-controlled, two-armed, parallel-group, multicentre trial. The study is designed to investigate the effects of pulsed infusions of levosimendan (6 h administration at 0.2 microg/kg/min every 2 weeks) on the composite endpoint (primary endpoint) comprising changes in functional capacity and QoL (20% or greater improvement in the 6 min walk test and 15% or higher score on the Kansas City Cardiomyopathy Questionnaire) at the end of the 24 week study period. In addition, short-term (8 weeks from randomization) and long-term (24 weeks from randomization) event-free survival (secondary endpoint) will be assessed. The LevoRep study aims to include 120 outpatients with advanced CHF.

Conclusion: LevoRep is the first prospective randomized trial to assess the effects of pulsed infusions of an inotrope on hard endpoints as well as on the safety in patients with advanced CHF on an outpatient basis. The results are expected to promote the development of evidence-based recommendations for the ambulatory management of patients with end-stage heart failure.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Health Status Indicators
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Hydrazones / administration & dosage
  • Hydrazones / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Outpatients
  • Pulsatile Flow
  • Pyridazines / administration & dosage
  • Pyridazines / therapeutic use*
  • Quality of Life
  • Research Design*
  • Simendan
  • Surveys and Questionnaires

Substances

  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • Simendan