E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic heart failure and left ventricular systolic dysfunction |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the minimum effective dose of Istaroxime, in patients requiring hospitalisation for chronic heart failure and left ventricular systolic dysfunction. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety, tolerability and efficacy of Istaroxime at different doses on invasive hemodynamic (blood pressure, heart rate, cardiac index, stroke work index, right atrial pressure, systemic and pulmonary resisitances), Echocardiographic and Doppler parameters. Istaroxime effects are to be assessed on neurohormonal parameters and renal function. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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%. |
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study will be pursued by monitoring PCWP from right heart catheterization. PCWP will be measured at baseline, after a suitable stabilization period and every hour during the infusion. PCWP data will then be collected at 30, 60 and 120 min after the end of infusion. Changes from pre-infusion to the end of infusion will be considered for the primary statistical analysis. A 5 mmHg reduction in PCWP will be considered clinically significant.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |