Safety and Efficacy Study to Evaluate the Effect of SLV320 on Renal Function in Patients With Worsening Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of IV SLV320 in acute heart failure patients with renal dysfunction.

Detailed Description
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The purpose of this study is to determine the efficacy and safety of IV SLV320 in acute heart failure patients with renal dysfunction.

Official Title
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A Double-Blind, Placebo-Controlled, Randomized, Multi-Center, Dose-Finding Study of SLV320, a Selective A1 Adenosine Receptor Antagonist, to Evaluate the Effect on Renal Function and Safety in Subjects Hospitalized With Acute Decompensated Heart Failure and Renal Dysfunction (Reno-Defend 1)

Conditions
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Acute Decompensated Heart Failure; Renal Dysfunction

Intervention / Treatment
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* Drug: SLV320
* Drug: SLV320
* Drug: SLV320
* Drug: SLV320
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Renal dysfunction defined as estimated eGFR of 20-80 mL/min; history of systolic or diastolic chronic heart failure of at least 14 days duration for which loop diuretic therapy has been prescribed; clinical evidence for volume overload; BNP ≥ 500 pg/mL or NT-pro-BNP > 2000 pg/mL; hospitalization. Exclusion Criteria Have low output syndrome, defined as having the need for treatment with I.V. inotropes or vasopressors; Need mechanical ventilation; Have significant stenotic valvular disease (severe aortic or mitral stenosis); 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 >120 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; Have acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: SLV320<br>* 1.25mg i.v. bid<br>|
| Experimental: 2<br> | Drug: SLV320<br>* 3.75mg i.v. bid<br>|
| Experimental: 3<br> | Drug: SLV320<br>* 7.5mg i.v. bid<br>|
| Experimental: 4<br> | Drug: SLV320<br>* 15.0mg i.v. bid<br>|
| Placebo Comparator: 5<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum creatinine from baseline to Day 14 |  | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare four SLV320 doses to placebo on the change in the following variables: Dyspnea (Likert Scale and PDA scale), eGFR (MDRD Formula), Subject Global Clinical Assessment Score, Urine Osmolality, Serum Osmolality |  | Up to Day 3 (Dyspnea); Up to Day 4 (Urine Osmolality); Up to Day 60 (eGFR, Subject Global Clinical Assessment Score, Serum Osmolality) | 
| 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 |  | Up to Day 14 | 
| To compare the effect of four I.V. doses of SLV320 with placebo on top of diuretic use |  | Up to Day 3 | 
| To compare the effect of four I.V. doses of SLV320 with placebo using a composite endpoint of all-cause mortality, cardiovascular hospitalization or hospitalization for worsening renal function, in time to event and frequency |  | Up to Day 180 | 
| To determine the pharmacokinetic profile of I.V. SLV320 |  | Up to Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLV320; Acute Decompensated Heart Failure (ADHF); chronic heart failure; renal failure; I.V. doses; hospitalization