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

Chronic Heart Failure (CHF) Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Renal Hemodynamic Effects of RLX030 and Placebo Infused for 24 Hours in Subjects With Chronic Heart Failure (CHF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01546532
• Other study ID #: CRLX030A2202
• Secondary ID: 2011-001588-37
• Status: Completed
• Phase: Phase 2
• Start date: February 2012
• Est. completion date: December 2012

Study information

• Verified date: February 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Heart Failure (CHF)
• Heart Failure

Intervention

Drug:
• RLX030
RLX030 as intravenous infusion for 24 hours.
• Placebo
Intravenous infusion of Placebo over 24 hours

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Goettingen
Germany	Novartis Investigative Site	Hamburg
Netherlands	Novartis Investigative Site	Deventer
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Sneek
Poland	Novartis Investigative Site	Grodzisk Mazowiecki
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Kraków
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Walbrzych
Poland	Novartis Investigative Site	Warszawa
United States	Novartis Investigative Site	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline, during and after the end of 24 hours infusion
Primary	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	Baseline, during and after the end of 24 hours infusion
Secondary	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.	Baseline, during and after the end of 24 hours of infusion
Secondary	Change over time in Diuresis	Urine samples will be collected for analyses.	During 24 hours of infusion and after the end of the infusion
Secondary	Change over time in calculated creatinine clearance	Urine samples will be collected for analyses.	During 24 hours of infusion and after the end of the infusion
Secondary	Change over time on fractional sodium excretion(natriuresis)	Urine samples will be collected for analyses.	During 24 hours of infusion and after the end of the infusion
Secondary	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 24 hours of infusion and after the end of the infusion
Secondary	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 24 hours of infusion and after the end of the infusion
Secondary	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	During 24 hours of infusion and after the end of the infusion
Secondary	Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf)Time	Blood will be collected from an indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	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 indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C24h)	Blood will be collected from an indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)following intravenous administration	Blood will be collected from an indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	Pharmacokinetics of RLX030: mean residence time (MRT)intravenous administration	Blood will be collected from an indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	Pharmacokinetics of RLX030: volume of distribution at steady state (Vss) following intravenous administration	Blood will be collected from an indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	Pharmacokinetics of RLX030: systemic clearance from serum (CL) following intravenous administration(natriuresis)	Blood will be collected from an indwelling catheter.	During 24 hours of infusion and for 24 hours after the end of infusion
Secondary	Corrected QT (QTc) Interval Using Fridericia's and Bazett's Formula	Continuous 12 lead Holter ECG monitoring for extraction of ECGs and analysis	Baseline, during the 24 hours of infusion and after the end of the infusion

External Links

•   Results for CRLX030A2202 from the Novartis Clinical Trials website