TJK was funded by a Wellcome Trust Intermediate Fellowship (Ref: 095898/Z/11/Z ). VKS was funded by Wellcome Trust/Scottish Translational Medicine and Therapeutics Initiative (Ref: WT085664, Personal No. JAF was funded by an Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship (AMS-CSF3-Fallowfield, ). Any questions will be answered by the Data Disclosure Office.įunding: The preclinical research work was independently conducted at the University of Edinburgh, with serelaxin supplied by Novartis Pharmaceuticals under Material Transfer Agreement (MTA). For access to study data, enquiries should be submitted to Novartis via and must follow the process outlined on the website.
#Labchart reader arithmetic smoothing trial
Data from the preclinical research is held by the University of Edinburgh and is available on request by contacting Data from the Novartis sponsored clinical trial (RLX030X2201) is held in the clinical database at Novartis. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant preclinical and clinical data are provided within the paper and its Supporting Information files. Received: SeptemAccepted: FebruPublished: February 28, 2017Ĭopyright: © 2017 Snowdon et al. Taal, Royal Derby Hospital, UNITED KINGDOM PLoS Med 14(2):Īcademic Editor: Maarten W. (2017) Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial.
The clinical study’s main limitations were the relatively small sample size and stable, well-compensated population.Ĭitation: Snowdon VK, Lachlan NJ, Hoy AM, Hadoke PWF, Semple SI, Patel D, et al. Administration of serelaxin was safe and well tolerated, with no detrimental effect on systemic blood pressure or hepatic perfusion. In the randomized clinical study, infusion of serelaxin for 120 min increased total renal arterial blood flow by 65% (95% CI 40%, 95% p < 0.001) from baseline. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT/eNOS/NO signaling pathway in the kidney. The primary endpoint was the change from baseline in total renal artery blood flow. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min.
Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction.
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