Long-Term Intermittent Administration of Levosimendan in Patients With Advanced Heart Failure (LAICA)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Martín J García González, Hospital Universitario de Canarias
ClinicalTrials.gov Identifier:
NCT00988806
First received: September 29, 2009
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to determine whether the treatment strategy of long-term intermittent every 30 days, continuous intravenous infusion for 24 hours of Levosimendan, associated to optimal contemporary treatment for advanced heart failure reduce the incidence of admission for heart failure worsening at 12 months follow up, compared with the strategy based solely in the optimal contemporary treatment for advanced heart failure.


Condition Intervention Phase
Advanced Heart Failure
Drug: Levosimendan
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Double-blind Randomized Placebo-controlled Study to Evaluate the Efficacy and Safety of Intermittent, Long-term Administration of Levosimendan in Patients With Advanced Heart Failure

Resource links provided by NLM:


Further study details as provided by Hospital Universitario de Canarias:

Primary Outcome Measures:
  • Evaluate the incidence of admission for heart failure worsening in patients with advanced heart failure, defined as first admission to emergency services or hospitalization more than 12 hours due to a heart failure worsening. [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time from randomization until first hospitalization for heart failure worsening. All-cause mortality. Major cardiac events. Serious adverse events. Changes in NYHA scale and quality of life of patients. To analyze the cost-effectiveness of treatment. [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 213
Study Start Date: November 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Levosimendan
infusion of levosimendan at doses of 0.1 mcg / kg / min for 24 hours.
Drug: Levosimendan

Patients included in the intervention group receive optimal drug therapy for heart failure symptoms and also infusion of levosimendan at doses of 0.1 mcg / kg / min for 24 hours every 30 days.

Failure to reach an appropriate level of heart failure compensation before the deadline of 30 days for the next study drug administration or placebo, the administration of them will be every 15 days. Thereafter, failure to reach an appropriate level of heart failure compensation for patients or worsen after two consecutive infusions of study drug or placebo every 15 days, proceed to open the code patient randomization and and apply the most appropriate treatment.

Placebo Comparator: Placebo
infusion of placebo for 24 hours.
Drug: Levosimendan

Patients included in the intervention group receive optimal drug therapy for heart failure symptoms and also infusion of levosimendan at doses of 0.1 mcg / kg / min for 24 hours every 30 days.

Failure to reach an appropriate level of heart failure compensation before the deadline of 30 days for the next study drug administration or placebo, the administration of them will be every 15 days. Thereafter, failure to reach an appropriate level of heart failure compensation for patients or worsen after two consecutive infusions of study drug or placebo every 15 days, proceed to open the code patient randomization and and apply the most appropriate treatment.

Drug: Placebo

Patients included in the placebo group receive optimal drug therapy for heart failure and also infusion of placebo at the same infusion rate as levosimendan doses of 0.1 mcg / kg / min for 24 hours every 30 days.

Failure to reach an appropriate level of heart failure compensation before the deadline of 30 days for the next study drug administration or placebo, the administration of them will be every 15 days. Thereafter, failure to reach an appropriate level of heart failure compensation for patients or worsen after two consecutive infusions of study drug or placebo every 15 days, proceed to open the code patient randomization and and apply the most appropriate treatment.


Detailed Description:

Aims: To evaluate the efficacy and safety of long-term, intermittent intravenous administration for 24 hours of Levosimendan for the treatment of advanced heart failure. Main end-point: incidence of admission due to decompensation, defined as first admission to emergency services or hospitalization more than 12 hours due to heart failure worsening.

Secondary end-points: major cardiac events, serious adverse events, change in NYHA scale at baseline, 30 days, 6 and 12 months; effects on inflammatory and neurohormonal activation in heart failure, identify factors associated with better survival of patients, quality of life, cost-effectiveness of treatment.

Study Design: Prospective, randomized, double-blind placebo controlled trial.

Scope of the study: patients with advanced heart failure.

Study Subjects: Patients over 18 years old with advanced HF of any etiology, with at least one admission for acute decompensation treated or treatable with Levosimendan within 6 months prior to randomization.

Interventions: a 24-hour infusion every 30 days of Levosimendan or placebo in addition to optimal pharmacological treatment for HF during 12 months.

Determinations: clinical monitoring, protocol-specified analytical determinations, echocardiographic assessment, invasive hemodynamic assessment, functional assessment by 6 min walk test in corridor, quality of life assessment at baseline, after 30 days, 6 months and 12 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age over 18
  • Severe symptoms of heart failure with dyspnea and/or fatigue at rest or minimal effort (functional class III and IV of NYHA)
  • Episodes of fluid retention (pulmonary or systemic venous congestion, peripheral edema) and/or low cardiac output at rest (peripheral hypoperfusion)
  • objective evidence of severe cardiac dysfunction determined by the presence of at least one of the following:
  • Left ventricular ejection fraction </= 30%
  • A severe impairment of cardiac function by echocardiography with Doppler transmitral flow pattern pseudonormal or restrictive.
  • A left ventricular filling pressure elevated (PCP> 16 mmHg and / or DBP average> 12 mm Hg for pulmonary artery catheterization)
  • Levels of BNP or NT-proBNP higher in the absence of noncardiac causes for this.
  • Severe impairment of functional capacity as evidenced by one of the following:
  • Inability to exercise
  • A distance <300 m or less in women and / or patients >/= 75 years in the 6-minute walk test
  • A test of myocardial oxygen consumption <12-14 ml / kg / min.
  • >/= 1 prior history of HF hospitalization in the previous 6 months
  • Presence of all the above criteria despite attempts to optimize therapy including diuretics, inhibitors of the renin-angiotensin-aldosterone system and beta-blockers, unless these drugs were not tolerated or were contraindicated, and cardiac resynchronization therapy when indicated.
  • consent to participate in the study.

Exclusion Criteria:

  • Levosimendan allergy or hypersensitivity.
  • Severe renal impairment (creatinine clearance <30 ml / min).
  • Severe liver impairment.
  • History of autoimmune disease.
  • Pregnancy.
  • Women of childbearing age not using adequate contraception (hormonal, IUD, barrier + spermicide)
  • Heart disease with significant obstructions to ventricular filling or emptying.
  • Severe hypotension (Systolic < 90 mmHg).
  • Tachycardia > 120 bpm or a history of torsion point type ventricular tachycardia.
  • Severe concomitant disease with decreased short-term prognosis.
  • Inability to give informed consent.
  • Participation in another study.
  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: NCT00988806

Locations
Spain
Department of Cardiology. Hospital Universitario de Canarias
La Laguna, S.C. de Tenerife, Spain, 38320
Sponsors and Collaborators
Hospital Universitario de Canarias
Investigators
Principal Investigator: Martín J García González, MD, PhD Hospital Universitario de Canarias. La Laguna. Tenerife. Spain
  More Information

Publications:
Responsible Party: Martín J García González, Consultant MD, PhD, Hospital Universitario de Canarias
ClinicalTrials.gov Identifier: NCT00988806     History of Changes
Other Study ID Numbers: LAICA Study 2009, EudraCT 2009-011441-11
Study First Received: September 29, 2009
Last Updated: September 17, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Universitario de Canarias:
Advanced heart failure
Levosimendan
Intermittent long-term infusions

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 September 22, 2014