Rationale and Design of a Randomized, Double-Blind, Placebo Controlled Multicenter Trial to Study Efficacy, Security, and Long Term Effects of Intermittent Repeated Levosimendan Administration in Patients with Advanced Heart Failure: LAICA study

Abstract

BackgroundAdvanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation.MethodsThe LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 μg/kg/min dose, without a loading dose, every 30 days, or placebo.ResultsThe main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events.ConclusionsThe LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Rehospitalization after intermittent levosimendan treatment in advanced heart failure patients: a meta‐analysis of randomized trials

“…The LAICA study aimed to test the effects of monthly 24‐h infusions of levosimendan on the incidence of in‐hospital admissions for acute decompensated HF in 97 patients in the advanced stages of the disease. This was a multicentre, prospective, randomized, double‐blind, placebo‐controlled, parallel‐group trial, with several additional secondary endpoints.…”

Reappraisal on pharmacological and mechanical treatments of heart failure

“…LEAF studied short-term intravenous infusion of levosimendan, which appears to be more effective than placebo for treating patients with HF complicated by AMI [49]. The result of this confusion may be that the composite endpoint events are not uniform, and LAICA [50] and LeoDOR [51] are warranted to confirm those findings.…”

“…Pharmacotherapy Tolvaptan TACTICS-HF [8], AQUAMARINE [9,10], Shirakabe et al [11], EVEREST [12], SECRET, QUEST, METEOR [13] Ivabradine SHIFT [14,15], INTENSIFY, ETHIC-AHF, Bagriy et al [17], CARVIVA HF [18] Sacubitril/valsartan PARADIGM-HF [19][20][21][22][23], PIONEER-HF [24,25], EVALUATE-HF [26], TRANSITION [27,28], PARAMOUNT [29,30], PARAGON-HF [31] Nebivolol SENIORS [33][34][35][36][37], Sessa et al [38], Brehm et al [39], ELANDD [40], CARNEBI [41] Levosimendan LIDO [42], SURVIVE [43], REVIVE [44], LevoRep [45], Zhang et al [46], LION-HEART [47], LEAF [48], Jia et al [49], LAICA [50], Leo-DOR [51] MRA Eplerenone: EPHESUS [75], EMPHASIS-HF [52][53][54][55]…”

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

“…Recently, intermittent levosimendan has been assessed in two double-blind, randomized, placebo-controlled trials, the LION-HEART and LAICA studies [47,48].…”

“…LAICA [48] was an Investigator Initiated Trial evaluating monthly 24-hour infusions of levosimendan for a year in addition to optimal medical therapy for reducing the incidence of hospitalization for acute decompensated HF in patients with advanced chronic AdHF. Secondary endpoints were cumulative incidence of hospitalization for acute decompensated HF and/or mortality at 30 days, and after 3, 6, and 12 month; the time-interval from randomization to first hospitalization for acute cardiac decompensation or death; incidence of adverse events; and changes in NYHA functional class over the one-year followup.…”