Renal Hemodynamic Effects of RLX030A in Subjects With Chronic Heart Failure (CHF)
This study has been completed.
Sponsor:
Novartis Pharmaceuticals
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
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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
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 May 19, 2013