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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01546532
First received: March 2, 2012
Last updated: February 7, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Chronic Heart Failure (CHF)
Drug: RLX030
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline, during and after the end of 24 hours infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, during and after the end of 24 hours infusion ] [ Designated as safety issue: No ]
    Serial blood and urine collections over time for determination of IOTH and its clearance respectively


Secondary Outcome Measures:
  • Change from baseline in filtration fraction (FF) in subjects with CHF after 24 hours infusion of RLX030 [ Time Frame: Baseline, during and after the end of 24 hours of infusion ] [ Designated as safety issue: No ]
    The filtration fraction (FF) is derived as the ratio of GFR divided by RBF in percent.

  • Change over time in Diuresis [ Time Frame: During 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: No ]
    Urine samples will be collected for analyses.

  • Change over time in calculated creatinine clearance [ Time Frame: During 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: No ]
    Urine samples will be collected for analyses.

  • Change over time on fractional sodium excretion(natriuresis) [ Time Frame: During 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: No ]
    Urine samples will be collected for analyses.

  • Central aortic systolic pressure-time curve [ Time Frame: During 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: No ]
    A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms

  • Radial augmentation index-time curve [ Time Frame: During 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: During 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    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) [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an indwelling catheter.

  • Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C24h) [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an indwelling catheter.

  • Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)following intravenous administration [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an indwelling catheter.

  • Pharmacokinetics of RLX030: mean residence time (MRT)intravenous administration [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an indwelling catheter.

  • Pharmacokinetics of RLX030: volume of distribution at steady state (Vss) following intravenous administration [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an indwelling catheter.

  • Pharmacokinetics of RLX030: systemic clearance from serum (CL) following intravenous administration(natriuresis) [ Time Frame: During 24 hours of infusion and for 24 hours after the end of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an indwelling catheter.

  • Corrected QT (QTc) Interval Using Fridericia's and Bazett's Formula [ Time Frame: Baseline, during the 24 hours of infusion and after the end of the infusion ] [ Designated as safety issue: No ]
    Continuous 12 lead Holter ECG monitoring for extraction of ECGs and analysis


Enrollment: 118
Study Start Date: February 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RLX030
RLX030 as intravenous infusion for 24 hours.
Drug: RLX030
RLX030 as intravenous infusion for 24 hours.
Placebo Comparator: Placebo
Placebo as intravenous infusion for 24 hours.
Drug: Placebo
Intravenous infusion of Placebo over 24 hours

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546532

Locations
United States, Maryland
Novartis Investigative Site
Baltimore, Maryland, United States
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Erlangen, Germany, 91054
Novartis Investigative Site
Goettingen, Germany, 37075
Novartis Investigative Site
Hamburg, Germany, 20246
Netherlands
Novartis Investigative Site
Deventer, Netherlands, 7416 SE
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Sneek, Netherlands, 8601 ZR
Poland
Novartis Investigative Site
Grodzisk Mazowiecki, Poland, 05-825
Novartis Investigative Site
Katowice, Poland, 40-637
Novartis Investigative Site
Krakow, Poland, 31-202
Novartis Investigative Site
Kraków, Poland, 31-501
Novartis Investigative Site
Lublin, Poland, 20-954
Novartis Investigative Site
Walbrzych, Poland, 58-309
Novartis Investigative Site
Warszawa, Poland, 04-628
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01546532     History of Changes
Other Study ID Numbers: CRLX030A2202, 2011-001588-37
Study First Received: March 2, 2012
Last Updated: February 7, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Novartis:
Heart failure
RLX030
hemodynamics
cardiovascular diseases

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 29, 2014