Renal Hemodynamic Effects of RLX030A in Subjects With Chronic Heart Failure (CHF)

Novartis Pharmaceuticals118 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

118

Conditions

Chronic Heart Failure (CHF)

Interventions

RLX030DRUG

RLX030 as intravenous infusion for 24 hours.

PlaceboDRUG

Intravenous infusion of Placebo over 24 hours

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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/exclusion criteria may apply.

Locations (15)

Novartis Investigative Site

Baltimore, Maryland, United States

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Erlangen, Germany

Outcomes

Primary Outcomes

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

Serial blood and urine collections over time for determination of PAH and its clearance respectively

Time frame: Baseline, during and after the end of 24 hours infusion

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

Serial blood and urine collections over time for determination of IOTH and its clearance respectively

Time frame: Baseline, during and after the end of 24 hours infusion

Secondary Outcomes

Change from baseline in filtration fraction (FF) in subjects with CHF after 24 hours infusion of RLX030

The filtration fraction (FF) is derived as the ratio of GFR divided by RBF in percent.

Time frame: Baseline, during and after the end of 24 hours of infusion

Change over time in Diuresis

Urine samples will be collected for analyses.

Time frame: During 24 hours of infusion and after the end of the infusion

Change over time in calculated creatinine clearance

Urine samples will be collected for analyses.

Time frame: During 24 hours of infusion and after the end of the infusion

Change over time on fractional sodium excretion(natriuresis)

Urine samples will be collected for analyses.

Time frame: During 24 hours of infusion and after the end of the infusion

Data from ClinicalTrials.gov

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Novartis Investigative Site

Göttingen, Germany

Novartis Investigative Site

Hamburg, Germany

Novartis Investigative Site

Deventer, Netherlands

Novartis Investigative Site

Groningen, Netherlands

Novartis Investigative Site

Sneek, Netherlands

Novartis Investigative Site

Grodzisk Mazowiecki, Poland

Novartis Investigative Site

Katowice, Poland

...and 5 more locations

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

Time frame: During 24 hours of infusion and after the end of the 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

Time frame: During 24 hours of infusion and after the end of the infusion

Number of patients with adverse events, serious adverse events and death

Monitoring of adverse events, serious adverse events and death from screening to end of study

Time frame: During 24 hours of infusion and after the end of the infusion

Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf)Time