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. - The Horizon-HF Trial

• Conditions: Chronic heart failure and left ventricular systolic dysfunction; MedDRA version: 8.1Level: LLTClassification code 10008908Term: Chronic heart failure

• Registration Number: EUCTR2005-004972-20-GR
• Lead Sponsor: Sigma-Tau i.f.r. S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-12
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Patients will be enrolled in the study during the first 48 hours of hospitalisation (screening period).

Screening period inclusion criteria:
- Capability of understanding the nature of the trial and willingness to participate as documented by signing the written informed consent form.
- Male or female patients aged between 18 and 85 years.
- Negative pregnancy test at screening, for women of childbearing potential only.
- Body weight less than or equal to 100 kg.
- Blood pressure not more than SAP150 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 Left Ventricular Ejection Fraction less than or equal to 35% documented by 2D-Echocardiogram, or radionuclide angiography or LV angiogram within 6 months prior to screening or at hospitalisation.
- the clinical condition of the patient is stailized within 48 hours form hospitalization and does 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
- a balloon-flotation pulmonary artery catherter insertion is feasible

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 Pulmonary Capillary Wedge Pressure (PCWP) greater than or equal to 20 mmHG.
- The last three consecutive determinations of PCWP, obtained during the stabilisation period, have to be in a maximum range of variability 0f 10%.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Ongoing treatment with oral or intravenous inotropes and/or inodilators (amrinone, digoxin, dopamine, dobutamine, enoximone, levosimendan, milrinone). 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.
- 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified