Chronic Heart Failure (CHF)
Conditions
Keywords
Heart failure, RLX030, hemodynamics, cardiovascular diseases
Brief summary
This study will assess the renal hemodynamic effect of RLX030 infusion in subjects with chronic heart failure. In addition safety and effects on renal function and biomarkers will be assessed.
Interventions
DRUGPlacebo
Intravenous infusion of Placebo over 24 hours
DRUGRLX030
RLX030 as intravenous infusion for 24 hours.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed. * Male and female heart failure patients with body weight \<160 kg, on standard therapy including a stable dose of furosemide 40-240 mg/day orally (p.o). or equivalent dose of loop diuretics, reduced systolic function (LVEF ≤ 45% measured within the past 6 months), BNP ≥ 100 pg/mL or NT-pro-BNP of ≥ 400 pg/mLNYHA Class II or III, and worsening symptoms, e.g. fatigue, dyspnea, breathlessness within 3 months * Mild to moderate renal impairment
Exclusion criteria
* Systolic blood pressure (SBP) \< 110 mm Hg at the time of randomization * Administration of intravenous radiographic contrast agent within 72 hours prior to randomization or acute contrast-induced nephropathy at the time of randomization * Current use of non-steroidal antiinflammatory drugs (NSAIDs) * Current or planned (through the completion of study drug infusion) treatment with any i.v. therapies, including vasodilators (including nesiritide), positive inotropic agents, vasopressors, levosimendan, or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device). * Clinically significant hepatic impairment defined as hepatic encephalopathy of any degree or total bilirubin \> 50 μmol/l (3 mg/dl) or, if patient is not on warfarin therapy, INR \> 2.0 (or Prothrombin Time \> 2 \* ULN) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in renal plasma flow (RPF) measured by Para-aminohippuric acid (PAH) clearance in subjects with CHF after 24 hours intravenous (i.v) infusion of RLX030 | Baseline, during and after the end of 24 hours infusion | Serial blood and urine collections over time for determination of PAH and its clearance respectively |
| Change from baseline in glomerular filtration rate (GFR) as measured by Iothalamate (IOTH) clearance in subjects with CHF after 24 hours i.v. infusion of RLX030 | Baseline, during and after the end of 24 hours infusion | Serial blood and urine collections over time for determination of IOTH and its clearance respectively |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of RLX030: mean residence time (MRT)intravenous administration | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Change from baseline in filtration fraction (FF) in subjects with CHF after 24 hours infusion of RLX030 | Baseline, during and after the end of 24 hours of infusion | The filtration fraction (FF) is derived as the ratio of GFR divided by RBF in percent. |
| Change over time in Diuresis | During 24 hours of infusion and after the end of the infusion | Urine samples will be collected for analyses. |
| Change over time in calculated creatinine clearance | During 24 hours of infusion and after the end of the infusion | Urine samples will be collected for analyses. |
| Change over time on fractional sodium excretion(natriuresis) | During 24 hours of infusion and after the end of the infusion | Urine samples will be collected for analyses. |
| Central aortic systolic pressure-time curve | During 24 hours of infusion and after the end of the infusion | A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms |
| Radial augmentation index-time curve | During 24 hours of infusion and after the end of the infusion | A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms |
| Number of patients with adverse events, serious adverse events and death | During 24 hours of infusion and after the end of the infusion | Monitoring of adverse events, serious adverse events and death from screening to end of study |
| Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf)Time | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C24h) | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)following intravenous administration | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Pharmacokinetics of RLX030: volume of distribution at steady state (Vss) following intravenous administration | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Pharmacokinetics of RLX030: systemic clearance from serum (CL) following intravenous administration(natriuresis) | During 24 hours of infusion and for 24 hours after the end of infusion | Blood will be collected from an indwelling catheter. |
| Corrected QT (QTc) Interval Using Fridericia's and Bazett's Formula | Baseline, during the 24 hours of infusion and after the end of the infusion | Continuous 12 lead Holter ECG monitoring for extraction of ECGs and analysis |
Countries
Germany, Netherlands, Poland, United States
Outcome results
None listed