A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the minimum effective dose of Istaroxime, in
      patients requiring hospitalization for deterioration of chronic heart failure and left
      ventricular systolic dysfunction. This goal will be reached by comparing the hemodynamic
      effect of three different doses of the drug versus placebo. Efficacy will be measured as a
      change in Pulmonary Capillary Wedge Pressure from pre-infusion to the last assessment at six
      hours intravenous infusion.Secondary objectives will be to evaluate safety, tolerability and
      efficacy on other main hemodynamic parameters, echocardiographic and echo-doppler
      measurements, plus preliminary pharmacokinetics of the drug.
    

Detailed description: 
      Congestive heart failure is one of the most common cardiovascular conditions and it is
      presently reaching epidemic proportions. The prevalence of chronic heart failure has risen
      specifically as a result of the increased longevity and longer survival after myocardial
      infarction. In 2003, over one million hospitalization with a primary diagnosis of heart
      failure occurred in the United States of America, and a similar number has been reported in
      Europe, too. At present, approximately 5 million Americans are estimated to suffer of this
      syndrome and the number is expected to continue to increase with the increase and aging of
      the population. Despite advances in treatment, the mortality remains high in U.S.A. as in
      Europe, with nearly three hundred thousands patients dying of CHF as the primary or
      contributory cause each year.

      The total number of hospital admissions approaches 3 million yearly when HF is listed as a
      primary or secondary diagnosis. Although these patients have a relatively low mortality
      during the hospitalization (less than 4%), the readmission rates within 60 days of discharge
      range from 20 to 30% and mortality within 60 days of discharge is 5 - 10%.

      The primary aim of acute treatment of worsening CHF is to alleviate the symptoms of
      congestion and edema, improve the hemodynamic profile, and preserve renal function without
      causing myocardial injury. Improved hemodynamics usually results in relief of primary
      symptoms like dyspnea and edema and in a consequent improved sense of wellbeing and mental
      status. The improvement in hemodynamics may persist after the pharmacological interventions
      used in the acute phase are withdrawn.

      The need in this setting is to decrease the filling pressures (RA pressure and PCWP),
      increase cardiac output, without increasing the heart rate and inducing/worsening atrial or
      ventricular arrhythmias. In addition, the agent should improve diastolic function, modulate
      the exaggerated neurohormonal responses to CHF and preserve/protect the viable but non
      contractile myocardium (e.g.: the hibernated myocardium). The agent should also facilitate
      the earlier start of life-saving therapies (e.g. beta - blockers).Pre-clinical data on
      Istaroxime show that this drug increases contractility without increasing heart rate and
      oxygen consumption; furthermore it is improving diastolic dysfunction and it not causing
      vasodilatation.
    

Intervention name(s): Istaroxime; Istaroxime; Istaroxime; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 0.5 microgram/kg/min IV for 6 hours; 1.0 microgram/kg/min IV for 6 hours; 1.5 microgram/kg/min IV for 6 hours; Placebo
Other intervention name(s): PST2744; PST2744; PST2744; placebo of PST2744
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Acute Heart Failure; Inotropes; Lusitropic agents; Istaroxime; PST2744