A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function (HORIZON-HF)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase II Study to Assess the Hemodynamic Effects of Istaroxime, a Novel Lusinotropic Agent, in Patients Hospitalized With Worsening Heart Failure and a Reduced Left Ventricular Systolic Function|
- To determine the minimum effective dose of ISTAROXIME by comparing the hemodynamic effect of 3 different doses of the drug versus placebo. Efficacy will be measured as a change in PCWP from right heart catheterization. [ Time Frame: 6 hours drug infusion ] [ Designated as safety issue: No ]
- safety, tolerability and efficacy on blood pressure, heart rate, cardiac index, stroke work index, right atrial pressure, systemic and pulmonary vascular resistances, Echocardiographic and Doppler parameters, neurohormonal parameters and renal function. [ Time Frame: 6 and 24 hours after start of infusion ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||August 2007|
|Primary Completion Date:||July 2007 (Final data collection date for primary outcome measure)|
Istaroxime dose of 0.5 microgram/kg body weight/minute of iv infusion for six ours
0.5 microgram/kg/min IV for 6 hours
Other Name: PST2744
Istaroxime dose of 1.0 microgram/kg body weight/minute of iv infusion for six ours
1.0 microgram/kg/min IV for 6 hours
Other Name: PST2744
Istaroxime dose of 1.5 microgram/kg body weight/minute of iv infusion for six ours
1.5 microgram/kg/min IV for 6 hours
Other Name: PST2744
Placebo Comparator: 4
Placebo iv infusion for six ours
Other Name: placebo of PST2744
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.
|Study Chair:||Mihai Gheorghiade, MD FACC||Northwestern University Feinberg School of Medicine - Chicago|
|Principal Investigator:||Witold Ruzyllo, MD||National Institute of Cardiology, Department of Coronary Artery Disease - Warsaw - POLAND|
|Principal Investigator:||Cezar Macarie, MD||Insitutul de Boli Cardiovasculare C.C. Iliescu Bucuresti, Bucharest - ROMANIA|
|Principal Investigator:||Dimitrios Th Kremastinos, MD||Second Cardiology Department, Athens University Medical School, University Hospital Attikon, Athens - GREECE|
|Principal Investigator:||Serban I Bubenek-Turconi, MD||First Anaesth. & Intensive Care Dept., CC Iliescu Heart Disease Institute, Bucharest - ROMANIA|
|Principal Investigator:||Maria Dorobantu, MD||Emergency Hospital "Loreasca", Bucharest - ROMANIA|
|Principal Investigator:||Jerzy Korewicki, MD||Institute of Cardiology, Warsaw, Poland|
|Principal Investigator:||Jaroslaw Drodz, MD||Hospital bieganskieko , Dept of Cardiology, Lodz - POLAND|
|Principal Investigator:||Piotr Ponikowski, MD||Iv Military Hospital, Wroclaw, POLAND|
|Principal Investigator:||John N Nanas, MD PhD||Alexandra University Hospital, Athens - GREECE|