Efficacy and Safety of Pulsed Infusions of Levosimendan in Outpatients With Advanced Heart Failure (LevoRep)

August 27, 2010 updated by: Medical University Innsbruck

Efficacy and Safety of Pulsed Infusions of Levosimendan in Outpatients With Advanced Heart Failure - A Multicenter, Double-blind, Placebo Controlled Prospective Trial With Two Arms

The purpose of this study is to compare the effects of a pulsed application of Levosimendan versus placebo on the composite end-point functional capacity and quality of life.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND Significant advances have been made in the treatment of congestive heart failure (CHF) in the past few years. Neurohumoral therapy with ACE-inhibitors, ß-blockers and aldosterone antagonists has been established to significantly reduce morbidity and mortality. However, despite the advances of modern therapy advanced CHF remains a syndrome with a poor prognosis. Additionally, this syndrome is associated with poor quality of life and leads to progressive debiliation and cardial cachexia. Repeat hospitalizations for acute heart failure are common among severe CHF patients. Besides the discomfort for the patients hospital admissions constitute the lion's share of the health expenditure for the heart failure syndrome.

Inotropic support is provided to patients suffering acute heart failure refractory to neurohumoral therapy. This approach is performed according to the AHA/ACC- as well as to ESC Guidelines for therapy of CHF. Inotropic therapy is targeted on hemodynamic stabilization, improvement of functional status, and reduction of rehospitalization.

Moreover, in many centres treatment with inotropes such as dobutamine and milrinone are an integral part of the applied bridge to transplant concept in severe heart failure patients. In fact, continuous or pulsed inotropic support in severe heart failure patients has been tested repeatedly in small clinical studies.

Intermittent ambulatory low dose administration of dobutamine versus conventional therapy did not improve functional capacity in the DICE-Trial. By contrast, several case series with different dose regimens of dobutamine indicated improvement of functional status.

TRIAL RATIONALE Based on its pharmacologic profile Levosimendan appears to be promising in the treatment of severe chronic heart failure functional NYHA class III/IV to improve quality of life and physical activity and to reduce hospital admissions for acute heart failure.

Repeat drug administration may be superior over a single shot therapy to maintain beneficial long-term results.

For economical reasons and for the sake of the patients comfort drug administration should ideally be managed on an outpatient basis rather than in the hospital. Therefore and for practical reasons, a time period of six hours for drug administration might be reasonable.

Dosing of the drug will be based on the experiences in the Russlan Trial and on a small case report by Martys. In the latter study serial administration of levosimendan for 6 hours (bolus of 12 mcg/kg followed by a continuous infusion of 0,1 μg/kg/min for 50min and 0,2 μg/kg/min for the next 5 hours) induced a significant fall of BNP.

In an outpatient setting, however, a bolus should be not be given for safety reasons.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Recruiting
        • Medical University Innsbruck
        • Contact:
        • Principal Investigator:
          • Gerhard Poelzl, MD
      • Linz, Austria, 4010
        • Recruiting
        • Krankenhaus der barmherzigen Schwestern
        • Contact:
        • Principal Investigator:
          • Peter Siostrzonek, MD
      • Linz, Austria, 4010
        • Recruiting
        • Allg. öffentliches Krankenhaus der Elisabethinen
        • Contact:
        • Principal Investigator:
          • Christian Ebner, MD
      • Linz, Austria, 4021
        • Recruiting
        • Allgemeine Krankenhaus der Stadt Linz
        • Contact:
        • Principal Investigator:
          • Franz Leisch, MD
      • Salzburg, Austria, 5020
        • Recruiting
        • Paracelsus Medical University Salzburg
        • Contact:
        • Principal Investigator:
          • Johann Altenberger, MD
      • St. Poelten, Austria, 3100
        • Recruiting
        • Landesklinikum St. Poelten
        • Contact:
        • Principal Investigator:
          • Rudolf Berger, MD
      • Vienna, Austria, 1150
        • Recruiting
        • Kaiserin Elisabeth Spital Vienna
        • Contact:
        • Principal Investigator:
          • Thomas Stefenelli, MD
      • Wels, Austria, 4600
        • Recruiting
        • Klinikum Wels Grieskirchen
        • Contact:
        • Principal Investigator:
          • Thomas Weber, MD
  • Greece
      • Athens, Greece, 11527
        • Recruiting
        • Hippokration General Hospital
        • Contact:
          • Ekaterini Avgeropoulo, MD
        • Principal Investigator:
          • Ekaterini Avgeropoulo, MD
      • Athens, Greece, 11527
        • Recruiting
        • G. Gennimatas General Hospital
        • Contact:
        • Principal Investigator:
          • Apostolos Karavidas, MD
      • Athens, Greece, 12461
        • Recruiting
        • Heart Failure Clinic, Attikon University Hospital
        • Principal Investigator:
          • John Parissis, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with chronic stable heart failure NYHA III and IV diagnosed at least 3 months before inclusion
  • 6-min.-walk-test < 350 meters
  • EF < 35 %
  • Age > 20 years
  • Optimized and individualised neurohormonal background therapy according to ESC-guidelines for the treatment of chronic heart failure.
  • Patient has signed informed consent

Exclusion Criteria:

  • Hospitalization for decompensated heart failure requiring i.v. diuretics within the last month before randomization
  • History of torsades des pointes
  • Allergy to Levosimendan or any of the excipients
  • Administration of inotropes in the last 4 weeks
  • Potassium <3,5 and >5,5 mmol/l
  • Systolic blood pressure <= 100 mmHg
  • Women at childbearing age without using effective contraceptives ( oral contraceptives, intrauterine contraceptive devices) unless surgical sterilisation has been undertaken.
  • Female patients who are pregnant or nursing
  • Creatinin Clearance < 30ml/min/m2
  • Severe anemia (Hb < 10 mg /dl)
  • Mechanical obstruction affecting the ventricular filling or the outflow or both
  • Patients with non compliance
  • Severe conditions, which make the patient unsuitable to participate in a study as judged by the investigator
  • Severe liver disease
  • Percutaneous coronary intervention within the last 1 months
  • Coronary bypass surgery within the last 3 months
  • Planned HTX within the next six months
  • Patient involved in another clinical trial
  • De-nove heart failure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Levosimendan
Chronic stable heart failure
Drug: Levosimendan
Levosimendan will be infused on an outpatient basis for six hours at a dosage of 0,2 μg/kg/min without a bolus
Placebo Comparator: Placebo
Chronic Stable Heart Failure
Drug: Placebo
Levosimendan will be infused on an outpatient basis for six hours at a dosage of 0,2 μg/kg/min without a bolus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
proportion of patients showing an improvement in the six-minutes walk test and a higher scoring in the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: 24 weeks
24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
effects of a pulsed application of levosimendan on event free survival
Time Frame: 8 weeks from randomization
8 weeks from randomization
effects of a pulsed application of levosimendan on event free survival
Time Frame: 24 weeks from randomization
24 weeks from randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University Innsbruck

Collaborators

Orion Corporation, Orion Pharma

Investigators

  • Principal Investigator: Johann Altenberger, MD, Paracelsus Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Anticipated)

August 1, 2011

Study Completion (Anticipated)

August 1, 2011

Study Registration Dates

First Submitted

February 8, 2010

First Submitted That Met QC Criteria

February 8, 2010

First Posted (Estimate)

February 9, 2010

Study Record Updates

Last Update Posted (Estimate)

August 30, 2010

Last Update Submitted That Met QC Criteria

August 27, 2010

Last Verified

August 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-007407-86

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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