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

December 11, 2020 updated by: Novartis Pharmaceuticals

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)

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

118

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10117
        • Novartis Investigative Site
      • Erlangen, Germany, 91054
        • Novartis Investigative Site
      • Goettingen, Germany, 37075
        • Novartis Investigative Site
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
  • Netherlands
      • Deventer, Netherlands, 7416 SE
        • Novartis Investigative Site
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Sneek, Netherlands, 8601 ZR
        • Novartis Investigative Site
  • Poland
      • 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
        • Novartis Investigative Site
  • United States
    • Maryland
      • Baltimore, Maryland, United States
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Change over time in Diuresis
Time Frame: During 24 hours of infusion and after the end of the infusion
Urine samples will be collected for analyses.
During 24 hours of infusion and after the end of the infusion
Change over time in calculated creatinine clearance
Time Frame: During 24 hours of infusion and after the end of the infusion
Urine samples will be collected for analyses.
During 24 hours of infusion and after the end of the infusion
Change over time on fractional sodium excretion(natriuresis)
Time Frame: During 24 hours of infusion and after the end of the infusion
Urine samples will be collected for analyses.
During 24 hours of infusion and after the end of the infusion
Central aortic systolic pressure-time curve
Time Frame: 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
During 24 hours of infusion and after the end of the infusion
Radial augmentation index-time curve
Time Frame: 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
During 24 hours of infusion and after the end of the infusion
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
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
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
Blood will be collected from an indwelling catheter.
During 24 hours of infusion and for 24 hours after the end of infusion
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

March 2, 2012

First Submitted That Met QC Criteria

March 6, 2012

First Posted (Estimate)

March 7, 2012

Study Record Updates

Last Update Posted (Actual)

December 19, 2020

Last Update Submitted That Met QC Criteria

December 11, 2020

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRLX030A2202
  • 2011-001588-37 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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