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

NCT ID: NCT01065194

Last Updated: 2010-08-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2011-08-31

Brief Summary

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.

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.

Conditions

Chronic Stable Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Levosimendan

Chronic stable heart failure

Group Type: EXPERIMENTAL

Levosimendan

Intervention Type: DRUG

Levosimendan will be infused on an outpatient basis for six hours at a dosage of 0,2 μg/kg/min without a bolus

Placebo

Chronic Stable Heart Failure

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Levosimendan will be infused on an outpatient basis for six hours at a dosage of 0,2 μg/kg/min without a bolus.

Interventions

Levosimendan

Levosimendan will be infused on an outpatient basis for six hours at a dosage of 0,2 μg/kg/min without a bolus

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

Medical University Innsbruck

OTHER

Sponsor Role: lead

Responsible Party

Department of Internal Medicine III / Cardiology

Principal Investigators

Johann Altenberger, MD

Role: PRINCIPAL_INVESTIGATOR

Paracelsus Medical University

Locations

Medical University Innsbruck

Innsbruck, , Austria

Site Status: RECRUITING

Allg. öffentliches Krankenhaus der Elisabethinen

Linz, , Austria

Site Status: RECRUITING

Krankenhaus der Barmherzigen Schwestern

Linz, , Austria

Site Status: RECRUITING

Allgemeine Krankenhaus der Stadt Linz

Linz, , Austria

Site Status: RECRUITING

Paracelsus Medical University Salzburg

Salzburg, , Austria

Site Status: RECRUITING

Landesklinikum St. Poelten

Sankt Pölten, , Austria

Site Status: RECRUITING

Kaiserin Elisabeth Spital Vienna

Vienna, , Austria

Site Status: RECRUITING

Klinikum Wels Grieskirchen

Wels, , Austria

Site Status: RECRUITING

G. Gennimatas General Hospital

Athens, , Greece

Site Status: RECRUITING

Hippokration General Hospital

Athens, , Greece

Site Status: RECRUITING

Heart Failure Clinic, Attikon University Hospital

Athens, , Greece

Site Status: RECRUITING

Countries

Austria; Greece

Central Contacts

Johann Altenberger, MD

Role: CONTACT

j.altenberger@salk.at

+436624482 ext. 57560

Gerhard Poelzl, MD

Role: CONTACT

gerhard.poelzl@uki.at

+43512504 ext. 81318

Facility Contacts

Gerhard Poelzl, MD

Role: primary

gerhard.poelzl@uki.at

+43512504 ext. 81318

Christian Ebner, MD

Role: primary

christian.ebner@elisabethinen.or.at

+4373276760

Michael Mori, MD

Role: primary

michael.mori@bhs.at

+437327677

Kurt Sihorsch, MD

Role: primary

kurt.sihorsch@akh.linz.at

+437327806 ext. 6235

Johann Altenberger, MD

Role: primary

j.altenberger@salk.at

+436624482 ext. 57560

Rudolf Berger, MD

Role: primary

rudolf.berger@stpoelten.lknoe.at

+432742300 ext. 14706

Lida Dimopoulos-Xicki, MD

Role: primary

Lida.Domopoulos-Xicki@wienkav.at

+43/198104 ext. 2108

Thomas Weber, MD

Role: primary

Thomas.Weber@klinikum-wegr.at

+437242415 ext. 2215

Apostolos Karavidas, MD

Role: primary

akaravid@yahoo.com

Ekaterini Avgeropoulo, MD

Role: primary

John Parissis, MD

Role: primary

jparissis@yahoo.com

References

Altenberger J, Parissis JT, Costard-Jaeckle A, Winter A, Ebner C, Karavidas A, Sihorsch K, Avgeropoulou E, Weber T, Dimopoulos L, Ulmer H, Poelzl G. Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: a multicentre randomized trial. Eur J Heart Fail. 2014 Aug;16(8):898-906. doi: 10.1002/ejhf.118. Epub 2014 Jun 11.

Reference Type: DERIVED

PMID: 24920349 (View on PubMed)

Other Identifiers

2008-007407-86

Identifier Type: -

Identifier Source: org_study_id