Hemodynamic Responses to RLX030 Infusion in Subjects With Acute Heart Failure

Study Overview
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Brief Summary
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This study will assess the hemodynamic effect of RLX030 infusion in subjects with acute heart failure. In addition safety and effects on renal function and biomarkers will be assessed.

Official Title
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A Multicenter, Double Blind, Randomized, Parallel Group, Placebo-controlled Study to Evaluate the Hemodynamic Responses to Intravenous RLX030 Infusion in Subjects With Acute Heart Failure

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: RLX030
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients hospitalized or requiring admission to hospital for management of acute heart failure within the previous 48 hours. Pulmonary wedge pressure above or equal to18 mmHg determined by right heart catheterization Exclusion Criteria: Systolic blood pressure below 115 mmHg Significant valvular diseases or arrythmias Acute coronary syndrome in previous 45 days Treatment with mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) Impaired renal or hepatic function Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 87 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RLX030<br>RLX030 as intravenous infusion for 20 hours | Drug: RLX030<br>* Intravenous infusion of RLX030 over 20 hrs<br>* Other names: *International Nonproprietary Name;|
| Placebo Comparator: Placebo<br>Matching placebo as intravenous infusion for 20 hours. | Drug: Placebo<br>* Intravenous infusion of placebo over 20 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak change from baseline of PCWP (pulmonary capillary wedge pressure) | Measurements will be made using a Swan-Ganz indwelling catheter | baseline, after 8 and 20 hrs treatment | 
| Peak change from baseline of CI (cardiac index) | Measurements will be made using a Swan-Ganz indwelling catheter | baseline, after 8 and 20 hrs treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change over time of PCWP (pulmonary capillary wedge pressure) | Measurements will be made using a Swan-Ganz indwelling catheter | During 20 hours of infusion and up to 4 hours after stop of infusion | 
| Change over time of systemic vascular resistance (SVR) | Measurements will be made using a Swan-Ganz indwelling catheter | During 20 hours of infusion and up to 4 hours after stop of infusion | 
| Change over time of pulmonary vascular resistance (PVR) | Measurements will be made using a Swan-Ganz indwelling catheter | During 20 hours of infusion and up to 4 hours after stop of infusion | 
| Change over time of pulmonary arterial pressure (PAP) | Hemodynamic measurements were made using a Swan-Ganz catheter when patients were in a supine position | During 20 hours of infusion and up to 4 hours after stop of infusion | 
| Change over time of pulmonary and peripheral oxygen saturation | Hemodynamic measurements were made using a Swan-Ganz catheter when patients were in a supine position | During 20 hours of infusion and up to 4 hours after stop of infusion | 
| Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf) | Blood will be collected from an in dwelling catheter. | During 20 hours of infusion and 24 hours after stop of infusion | 
| Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) | Blood will be collected from an in dwelling catheter. | During 20 hours of infusion and 24 hours after stop of infusion | 
| Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C20h) | Blood will be collected from an in dwelling catheter. | During 20 hours of infusion and 24 hours after stop of infusion | 
| Pharmacokinetics of RLX030: terminal elimination half-life (T1/2) | Blood will be collected from an in dwelling catheter. | During 20 hours of infusion and 24 hours after stop of infusion | 
| Pharmacokinetics of RLX030: mean residence time (MRT) | Blood will be collected from an in dwelling catheter. | During 20 hours of infusion and 24 hours after stop of infusion | 
| Pharmacokinetics of RLX030: volume of distribution at steady state following intravenous administration | Blood will be collected from an in dwelling catheter. | During 20 hours of infusion and 24 hours after stop of infusion | 
| Change over time on calculated creatinine clearance | Urine samples will be collected for analyses. | During 20 hours of infusion and 4 hours after stop of infusion | 
| Change over time in Diuresis | Urine samples will be collected for analyses. | During 20 hours of infusion and 4 hours after stop of infusion | 
| Central aortic systolic pressure-time curve | A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms | During 20 hours of infusion and 24 hours after stop of infusion | 
| Radial augmentation index-time curve | A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms | During 20 hours of infusion and 24 hours after stop of infusion | 
| Number of patients with adverse events, serious adverse events and death | Adverse events will be assessed by signs/symptoms, clinical laboratory and electrocardiographs. | During 20 hours of infusion and 24 hours after stop of infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, RLX030, Hemodynamics, Cardiovascular Diseases