Clinical trial NCT01546532: Renal Hemodynamic Effects of RLX030A in Subjects With Chronic Heart Failure (CHF)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Heart Failure (CHF)
Keywords: Heart failure
RLX030
hemodynamics
cardiovascular diseases
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline, during and after the end of 24 hours infusion
measure: 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
timeFrame: Baseline, during and after the end of 24 hours infusion
Secondary outcomes:
measure: Change from baseline in filtration fraction (FF) in subjects with CHF after 24 hours infusion of RLX030
timeFrame: Baseline, during and after the end of 24 hours of infusion
measure: Change over time in Diuresis
timeFrame: During 24 hours of infusion and after the end of the infusion
measure: Change over time in calculated creatinine clearance
timeFrame: During 24 hours of infusion and after the end of the infusion
measure: Change over time on fractional sodium excretion(natriuresis)
timeFrame: During 24 hours of infusion and after the end of the infusion
measure: Central aortic systolic pressure-time curve
timeFrame: During 24 hours of infusion and after the end of the infusion
measure: Radial augmentation index-time curve
timeFrame: During 24 hours of infusion and after the end of the infusion
measure: Number of patients with adverse events, serious adverse events and death
timeFrame: During 24 hours of infusion and after the end of the infusion
measure: Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf)Time
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C24h)
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)following intravenous administration
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Pharmacokinetics of RLX030: mean residence time (MRT)intravenous administration
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Pharmacokinetics of RLX030: volume of distribution at steady state (Vss) following intravenous administration
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Pharmacokinetics of RLX030: systemic clearance from serum (CL) following intravenous administration(natriuresis)
timeFrame: During 24 hours of infusion and for 24 hours after the end of infusion
measure: Corrected QT (QTc) Interval Using Fridericia's and Bazett's Formula
timeFrame: Baseline, during the 24 hours of infusion and after the end of the infusion
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Goettingen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Deventer
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Sneek
country: Netherlands
facility: Novartis Investigative Site
city: Grodzisk Mazowiecki
country: Poland
facility: Novartis Investigative Site
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Kraków
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Walbrzych
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Voors AA, Dahlke M, Meyer S, Stepinska J, Gottlieb SS, Jones A, Zhang Y, Laurent D, Slart RH, Navis GJ. Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study. Circ Heart Fail. 2014 Nov;7(6):994-1002. doi: 10.1161/CIRCHEARTFAILURE.114.001536. Epub 2014 Oct 6.