Efficacy and Safety of Pulsed Infusions of Levosimendan in Outpatients With Advanced Heart Failure (LevoRep)
Recruitment status was: Recruiting
|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|
- 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 ]
- 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 ]
|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)|
Chronic stable heart failure
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
Levosimendan will be infused on an outpatient basis for six hours at a dosage of 0,2 μg/kg/min without a bolus.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01065194
|Medical University Innsbruck|
|Innsbruck, Austria, 6020|
|Allg. öffentliches Krankenhaus der Elisabethinen|
|Linz, Austria, 4010|
|Krankenhaus der Barmherzigen Schwestern|
|Linz, Austria, 4010|
|Allgemeine Krankenhaus der Stadt Linz|
|Linz, Austria, 4021|
|Paracelsus Medical University Salzburg|
|Salzburg, Austria, 5020|
|Landesklinikum St. Poelten|
|St. Poelten, Austria, 3100|
|Kaiserin Elisabeth Spital Vienna|
|Vienna, Austria, 1150|
|Klinikum Wels Grieskirchen|
|Wels, Austria, 4600|
|G. Gennimatas General Hospital|
|Athens, Greece, 11527|
|Hippokration General Hospital|
|Athens, Greece, 11527|
|Heart Failure Clinic, Attikon University Hospital|
|Athens, Greece, 12461|
|Principal Investigator:||Johann Altenberger, MD||Paracelsus Medical University|