E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects Hospitalized with Acute Decompensated Heart Failure and Renal Dysfunction |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007554 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10038443 |
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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 compare the effect of four intravenous (I.V.) SLV320 doses with placebo on the change in serum creatinine from Baseline to Day 14. |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of four I.V. SLV320 doses with placebo on the change in the following variables from Baseline to various time points: Dyspnea (Likert Scale,Provocative Dyspnea Assessment [PDA]); serum creatinine; plasma cystatin C; estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD] formula); Subject Global Clinical Assessment Score; osmolality; serum osmolality; blood urea nitrogen (BUN); urea; sodium and potassium in urine; sodium and potassium in serum; troponin I, BNP. 2. To compare the effect of four I.V. doses of SLV320 with placebo using the trichotomous endpoint of treatment success, treatment failure, or no change (see protocol, pp.2-3) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Sono previste delle indagini opzionali sui marcatori biologici
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E.3 | Principal inclusion criteria |
1. Be capable of understanding the nature of the study and be willing to participate, as documented by signed written informed consent or signed informed consent by a legally authorized representative. 2. Be 18 years or older (male or female). 3. If female, be surgically sterile (bilateral oophorectomy and/or hysterectomy) or be at least one year postmenopausal as judged by the Investigator. 4. Have renal dysfunction (defined as estimated eGFR of 2080 mL/min [Cockcroft-Gault formula]). 5. Have BNP ≥400 pg/mL or NT-pro-BNP >2000 pg/mL. 6. Have a history of systolic or diastolic chronic heart failure of at least 14 days duration for which loop diuretic therapy has been prescribed. 7. Have clinical evidence of volume overload manifested by at least two of the following features: (a) dyspnea (b) rales (c) peripheral edema and/or pre-sacral edema (d) increased jugular venous distension (>8 cm) (e) chest X-ray consistent with CHF. 8. Require hospitalization for treatment of the current episode of ADHF with I.V. diuretics and − Have received at least 40 mg I.V. furosemide (or equivalent) for the treatment of the current episode of ADHF prior to the start of the initial study drug infusion unless a rationale for a lower dose is provided by the enrolling Investigator, and − Receives the first study treatment within 24 hours (± four hours) following presentation to the hospital (including the emergency department) for this episode of ADHF. 9. Anticipated need for I.V. furosemide ≥40 mg/day (or equivalent dose of I.V. loop diuretic) for at least 24 hours after start of study drug. |
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E.4 | Principal exclusion criteria |
Are women of child-bearing potential. 2. Have low output syndrome, defined as having the need for treatment with I.V. inotropes or vasopressors. 3. Have systolic blood pressure <95 mmHg at the time of randomization. 4. Have body temperature >38C (100.4F) at the time of randomization. 5. Need mechanical ventilation. 6. Have significant stenotic valvular disease (severe aortic or mitral stenosis). 7. Have clinical evidence of acute coronary syndromes in the two weeks prior to screening. 8. Have myocardial infarction or hemodynamically destabilizing significant arrythmias (ventricular tachycardia, bradyarrythmias with slow ventricular rate [<45 bpm] or atrial fibrillation/flutter with a rapid ventricular response of >130 bpm), or electrocardiographic evidence of 2nd degree heart block (Mobitz Type II) or 3rd degree AV-block in the absence of a pacemaker, within 30 days of screening. 9. Have acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy. 10. Have serum potassium <3.5 mEq/L and/or serum sodium <130 mEq/L. Serum potassium 3.03.4 mEq/L will be allowed if parenteral supplemental potassium is being administered. 11. Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &#8805;3 times the upper limit of normal; and/or total bilirubin >3 mg/dL. 12. Have clinically significant laboratory abnormalities or medical conditions which, in the opinion of the Investigator, make them unsuitable for evaluation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to compare the difference between the SLV320 doses and placebo in the change in serum creatinine from Baseline to Day 14. The null hypothesis states that there is no difference in the change from Baseline to Endpoint between any of the SLV320 doses and placebo. For each of the four SLV320 doses the alternative hypothesis states that the mean difference in the change from Baseline to Endpoint between the SLV320 dose and placebo is not zero. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 85 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
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 | 1 |