NCT01290146

Brief Summary

The purpose of this study is to compare in patients with Advanced Chronic Heart Failure the effects of Levosimendan versus diuretic (single 24-hour infusion) applied at the early detection of impending destabilization on hospitalization-free survival during 12 months. Patients with advanced chronic heart failure (ACHF) have a short term reduced life expectancy with recurrent hospital admissions for clinical exacerbations. Levosimendan improves contractility by calcium-dependent binding to troponin C, determines vasodilation of the coronary arteries and systemic resistance vessels, thus decreasing preload and afterload, while exerting a protective effect on the myocardium against ischemia-reperfusion damage. In randomized clinical trials of acute heart failure patients, levosimendan improved hemodynamics and patients' quality of life and decreased natriuretic peptide plasma levels, with no excess mortality The study will assess whether the administration of levosimendan (single 24-hour infusion) at the early detection of deterioration may reduce frequency and duration of hospital admissions, improve functional status and quality of life in ACHF patients, with respect to diuretic infusion.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Feb 2011

Longer than P75 for phase_3

Geographic Reach
1 country

22 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2011

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

February 3, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 4, 2011

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2015

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2017

Completed
Last Updated

April 10, 2017

Status Verified

April 1, 2017

Enrollment Period

4.3 years

First QC Date

February 3, 2011

Last Update Submit

April 7, 2017

Conditions

Advanced Chronic Heart Failure

Keywords

Heart FailureLevosimendanInotropic agentsPhosphodiesterase InhibitorsVasodilatorsDiuretics

Outcome Measures

Primary Outcomes (1)

  • Number of days alive free of Transplant and out-of-hospital (DAOH)

    Measured at 12 months

Secondary Outcomes (8)

  • Incidence of acute renal dysfunction

    Measured at at 24 hours since inception of randomized treatment for acute worsening HF

  • All cause mortality, hospital readmission and unscheduled office and emergency department visits for ADCHF

    Measured at 12 months

  • BNP changes

    Measured at at end-of- study and at each eventual destabilization

  • Number of hospital admissions for acute worsening HF

    Measured at 12 months

  • Costs

    Measured at 12 months

  • +3 more secondary outcomes

Study Arms (2)

Diuretics

ACTIVE COMPARATOR

Patients randomized to diuretics receive a 24-hour diuretic infusion with a maximum cumulative dose up to 200 mg furosemide/24 h

Drug: Diuretics

Levosimendan

EXPERIMENTAL

Patients randomized to Levosimendan receive a 24-hour levosimendan infusion with NO prior bolus injection. Starting doses will be based on baseline SBP levels * SBP ≥ 85-99mmHg: 0.05 mcg/kg/min * SBP ≥100 mmHg: 0.1 mcg/kg/min

Drug: Levosimendan

Interventions

DiureticsDRUG

Patients randomized to diuretics receive a 24-hour diuretic infusion with a maximum cumulative dose up to 200 mg furosemide/24 h

Diuretics
LevosimendanDRUG

Patients randomized to Levosimendan receive a 24-hour levosimendan infusion with NO prior bolus injection. Starting doses will be based on baseline SBP levels * SBP ≥ 85-99mmHg: 0.05 mcg/kg/min * SBP ≥100 mmHg: 0.1 mcg/kg/min

Levosimendan

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent
  • Systolic dysfunction (LVEF ≤ 35% by echo assessment within 6 months before enrolment)
  • No requirement for hospital admission for diagnostic work up or elective treatment to define etiology and/or treatment plan
  • Already on optimal standard HF treatment based on individual tolerance, including cardiac resynchronization therapy (CRT)/ICD device according to current guidelines
  • At least 2 hospital admissions for HF in the 6 months before enrolment, the most recent one within 30-90 days before enrolment with requirement for inotrope administration

You may not qualify if:

  • Participant in other studies in the last 30 days
  • Life expectancy \< 1 year for comorbid conditions other than HF
  • Pregnancy, lactation, childbearing potential unless on adequate contraception
  • Acute coronary syndromes, percutaneous or surgical revascularization, valve surgery performed within 8 weeks before enrolment
  • Planned percutaneous or surgical procedures (except for heart transplantation)
  • CRT within 6 months before enrolment
  • Cardiogenic shock
  • Supine systolic BP \< 85 mmHg
  • Severe liver insufficiency (\>three-fold increase in AST-ALT )
  • Sever chronic kidney dysfunction (estimated GFR \< 30 ml/min)
  • Sustained ventricular tachycardia
  • Severe chronic or current acute infection (temperature \>38 C, WBC \>15,000/mm3)
  • Severe chronic obstructive pulmonary disease (FEV1 \<30% predicted or on oxygen therapy)
  • Severe persistent anemia (Hb \< 10 g/l))
  • ACHF exacerbation due to conditions requiring specific treatment (e.g. anemia, atrial fibrillation, supraventricular tachycardia ) Documented low compliance or unavailable for programmed follow-up visits and phone contact

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

Ospedali Riuniti di Ancona Cardiology Presidio Lancisi

Ancona, Ancona, 60020, Italy

Location

Azienda Ospedaliero-Universitaria, Consorziale Policlinico di Bari, U.O. Cardiologia Universitaria, Dipartimento Emergenza e Trapianti di Organi

Bari, Bari, Italy

Location

Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge

Cassano Murge, Bari, 70020, Italy

Location

Ospedali Riuniti di Bergamo Cardiovascular Medicine

Bergamo, Bergamo, 24128, Italy

Location

Ospedale Brotzu Cardiology

Cagliari, Cagliari, 09134, Italy

Location

Ospedale Sant'Anna Cardiology

Como, Como, 22100, Italy

Location

Ospedale SS Annunziata Cardiology

Cosenza, Cosenza, 87100, Italy

Location

Istituti Ospitalieri di Cremona Cardiology

Cremona, Cremona, 26100, Italy

Location

Ospedale Santa Maria Nuova Cardiology

Florence, Firenze, 50100, Italy

Location

Ospedale Vito Fazzi

Lecce, Lecce, 73199, Italy

Location

Istituto Auxologico Italiano - IRCCS Clinical Cardiology Cardiovascular Department

Milan, Milan, 20148, Italy

Location

Azienda Ospedaliera Niguarda Heart Failure and Heart Transplant Program

Milan, Milan, 20162, Italy

Location

Azienda Ospedaliera S. Gerardo Hear Failure and Cardiomyopathy Clinic

Monza, Monza, 20052, Italy

Location

Gruppo Policlinico di Monza Clinical Cardiology and Heart Failure Unit Cardiology Department

Monza, Monza, 20052, Italy

Location

Ospedale Santa Maria della Misericordia Cardiology

Perugia, Perugia, 06156, Italy

Location

Ospedale Guglielmo da Saliceto Cardiology Department

Piacenza, Piacenza, 29100, Italy

Location

Azienda Ospedaliera San Camillo-Forlanini, Cardiology, Heart Failure Clinic

Roma, Roma, 00151, Italy

Location

Università di Roma Sapienza Dipartimento di Scienze Cardiovascolari e Respiratorie

Roma, Roma, 00161, Italy

Location

Azienda Ospedaliera San Giovanni- Addolorata 1st Cardiology Unit

Roma, Roma, 00184, Italy

Location

Ospedale Santo Spirito, Cardiology

Roma, Roma, 00193, Italy

Location

Azienda Ospedaliero-Universitaria, Ospedale di Cattinara Cardiology

Trieste, Trieste, 34149, Italy

Location

Ospedale di Circolo e Fondazione Macchi Cardiology

Varese, Varese, 21100, Italy

Location

MeSH Terms

Conditions

Heart Failure

Interventions

DiureticsSimendan

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Natriuretic AgentsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesHydrazonesHydrazinesOrganic ChemicalsPyridazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Fabrizio Oliva, MD

    Heart Failure Heart Transplant Program, Cardiovascular Department, Niguarda Hospital, Milan, Italy

    STUDY CHAIR

  • Michele Senni, MD

    Cardiovascular Medicine Ospedali Riuniti, Bergamo, Italy

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 3, 2011

First Posted

February 4, 2011

Study Start

February 1, 2011

Primary Completion

June 1, 2015

Study Completion

March 1, 2017

Last Updated

April 10, 2017

Record last verified: 2017-04

Locations

IT(22)