A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function

• Status: Completed
• Trial end date: 2007-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: sigma-tau i.f.r. S.p.A.
• Collaborator: MDS Pharma Services

Criteria

Inclusion Criteria:

• Signing of a written informed consent form.

• Male or female patients aged between 18 and 85 years.

• Negative pregnancy test at screening, for women of childbearing potential.

• Body weight less or equal to 100 kg.

• Blood pressure not more than SAP=150 or DAP=90 mmHg.

• Heart rate in the range of 60-110 bpm

• Adequate Echo window available.

• Hospital admission to a monitored bed with a primary diagnosis of worsening of heart failure and LV Ejection Fraction less or equal to 35% documented by 2D-Echocardiogram, or radionuclide angiography or LV angiogram within 6 months prior to screening or at hospitalization.

• the clinical condition of the patient are stabilized within 48 hours from hospitalization and do not require continuous iv drug treatments

• no need for additional new oral treatments or any intravenous treatment administration over the following 8 hours is foreseen

Randomisation period inclusion criteria:

• Any residual sign of heart failure (e.g.: Jugular Venous Distension, and/or Rales and/or Peripheral Oedema) associated with a PCWP more or equal to 20 mmHg,

• The last three consecutive determinations of PCWP, obtained during the stabilization period, have to be in a maximum range of variability of 10%.

Exclusion Criteria:

• Ongoing treatment with oral or intravenous inotropes and/or inodilators.

• Patient treated with digoxin within the last week, can be randomised if the plasma concentration of digoxin are tested before randomisation and its value will be less than 0.5 ng/ml.

• Intermittent inotropes administration within 2 weeks.

• Symptoms of Heart Failure at randomization e.g.: dyspnoea

• Systolic blood pressure < 90 mmHg.

• Atrial fibrillation within 2 weeks.

• Left Ventricular Bundle Branch Block

• Cardiogenic shock or mechanical ventilation.

• Creatinine level > 3.0 mg/dl or requiring dialysis treatment.

• Left ventricular failure primarily from uncorrected obstructive valvular disease, hypertrophic obstructive cardiomyopathy, restrictive/obstructive cardiomyopathy, uncorrected thyroid disease, known acute myocarditis, known amyloid cardiomyopathy.

• Artificial heart valve.

• Electrical device implanted (ICD, CRT)

• Evidence of acute coronary syndrome within 3 months.

• History of stroke or transient ischemic attack in the 6 months prior to screening.

• History of sustained ventricular tachycardia.

• Coronary by-pass grafting or PTCA within the last 30 days

• INR > 1.5.

• Status post successful cardiac resuscitation.

• Serum K < 3.5 mEq/l or > 5.3 mEq/l just prior to treatment.

• ALT, AST > 3 times the upper normal limit just prior to treatment.

• Hemoglobin < 10 g/dl (either gender) just prior to treatment.

• Other clinically significant laboratory or medical conditions, which in the opinion of the Investigator make the patient unsuitable for evaluation in the study.

• Anticipated survival of less than 2 months for concomitant diseases.