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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Medical University Innsbruck.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Orion Corporation, Orion Pharma
Information provided by:
Medical University Innsbruck
ClinicalTrials.gov Identifier:
NCT01065194
First received: February 8, 2010
Last updated: August 27, 2010
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Chronic Stable Heart Failure
Drug: Levosimendan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Medical University Innsbruck:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • effects of a pulsed application of levosimendan on event free survival [ Time Frame: 8 weeks from randomization ] [ Designated as safety issue: No ]
  • effects of a pulsed application of levosimendan on event free survival [ Time Frame: 24 weeks from randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: August 2009
Estimated Study Completion Date: August 2011
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01065194

Contacts
Contact: Johann Altenberger, MD +436624482 ext 57560 j.altenberger@salk.at
Contact: Gerhard Poelzl, MD +43512504 ext 81318 gerhard.poelzl@uki.at

Locations
Austria
Medical University Innsbruck Recruiting
Innsbruck, Austria, 6020
Contact: Gerhard Poelzl, MD    +43512504 ext 81318    gerhard.poelzl@uki.at   
Principal Investigator: Gerhard Poelzl, MD         
Krankenhaus der Barmherzigen Schwestern Recruiting
Linz, Austria, 4010
Contact: Michael Mori, MD    +437327677    michael.mori@bhs.at   
Principal Investigator: Peter Siostrzonek, MD         
Allg. öffentliches Krankenhaus der Elisabethinen Recruiting
Linz, Austria, 4010
Contact: Christian Ebner, MD    +4373276760    christian.ebner@elisabethinen.or.at   
Principal Investigator: Christian Ebner, MD         
Allgemeine Krankenhaus der Stadt Linz Recruiting
Linz, Austria, 4021
Contact: Kurt Sihorsch, MD    +437327806 ext 6235    kurt.sihorsch@akh.linz.at   
Principal Investigator: Franz Leisch, MD         
Paracelsus Medical University Salzburg Recruiting
Salzburg, Austria, 5020
Contact: Johann Altenberger, MD    +436624482 ext 57560    j.altenberger@salk.at   
Principal Investigator: Johann Altenberger, MD         
Landesklinikum St. Poelten Recruiting
St. Poelten, Austria, 3100
Contact: Rudolf Berger, MD    +432742300 ext 14706    rudolf.berger@stpoelten.lknoe.at   
Principal Investigator: Rudolf Berger, MD         
Kaiserin Elisabeth Spital Vienna Recruiting
Vienna, Austria, 1150
Contact: Lida Dimopoulos-Xicki, MD    +43/198104 ext 2108    Lida.Domopoulos-Xicki@wienkav.at   
Principal Investigator: Thomas Stefenelli, MD         
Klinikum Wels Grieskirchen Recruiting
Wels, Austria, 4600
Contact: Thomas Weber, MD    +437242415 ext 2215    Thomas.Weber@klinikum-wegr.at   
Principal Investigator: Thomas Weber, MD         
Greece
Heart Failure Clinic, Attikon University Hospital Recruiting
Athens, Greece, 12461
Contact: John Parissis, MD       jparissis@yahoo.com   
Principal Investigator: John Parissis, MD         
Hippokration General Hospital Recruiting
Athens, Greece, 11527
Contact: Ekaterini Avgeropoulo, MD         
Principal Investigator: Ekaterini Avgeropoulo, MD         
G. Gennimatas General Hospital Recruiting
Athens, Greece, 11527
Contact: Apostolos Karavidas, MD       akaravid@yahoo.com   
Principal Investigator: Apostolos Karavidas, MD         
Sponsors and Collaborators
Medical University Innsbruck
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Johann Altenberger, MD Paracelsus Medical University Salzburg
  More Information

No publications provided

Responsible Party: Medical University Innsbruck, Department of Internal Medicine III / Cardiology
ClinicalTrials.gov Identifier: NCT01065194     History of Changes
Other Study ID Numbers: 2008-007407-86
Study First Received: February 8, 2010
Last Updated: August 27, 2010
Health Authority: Austria: Agency for Health and Food Safety
Greece: National Organization of Medicines

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Simendan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cardiotonic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014