Adriaan A Voors1, Marion Dahlke2, Sven Meyer2, Janina Stepinska2, Stephen S Gottlieb2, Andrew Jones2, Yiming Zhang2, Didier Laurent2, Riemer H J A Slart2, Gerjan J Navis2. 1. From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.). a.a.voors@umcg.nl. 2. From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
Abstract
BACKGROUND:Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association Class II to III chronic heart failure, left ventricular ejection fraction ≤45%, and estimated glomerular filtration rate (GFR) 30 to 89 mL/min per 1.73 m(2) receivedintravenous serelaxin 30 μg/kg per day or placebo for 24 hours. Primarily, we assessed the difference between serelaxin and placebo on renal plasma flow (para-aminohippuric acid clearance) and GFR (iothalamate clearance) over 8 to 24 hours. All 22 patients from 1 clinical site were excluded from primary analyses before unblinding because of implausible measurements. The primary analysis comprised 65 patients, mean age was 68 (±10) years, 89% were male, mean estimated GFR was 64 (±19) mL/min per 1.73 m(2), and 34% had New York Heart Association Class III symptoms. Renal plasma flow increased by 29% with serelaxin and 14% with placebo (13% relative increase with serelaxin; P=0.0386), whereas GFR changes did not differ significantly during 8 to 24 hours. Filtration fraction increased by 36% with serelaxin and 62% with placebo (16% relative decrease with serelaxin; P=0.0019) during 8 to 24 hours. Changes in systolic blood pressure were largely similar, and creatinine clearance did not differ between groups. Adverse event rates were similar with serelaxin (20.5%) and placebo (25.0%). CONCLUSIONS: In patients with chronic heart failure, serelaxin increased renal plasma flow and reduced the increase in filtration fraction compared with placebo, but did not affect GFR. These results suggest beneficial renal hemodynamic effects in patients with chronic heart failure. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01546532.
RCT Entities:
BACKGROUND:Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association Class II to III chronic heart failure, left ventricular ejection fraction ≤45%, and estimated glomerular filtration rate (GFR) 30 to 89 mL/min per 1.73 m(2) received intravenous serelaxin 30 μg/kg per day or placebo for 24 hours. Primarily, we assessed the difference between serelaxin and placebo on renal plasma flow (para-aminohippuric acid clearance) and GFR (iothalamate clearance) over 8 to 24 hours. All 22 patients from 1 clinical site were excluded from primary analyses before unblinding because of implausible measurements. The primary analysis comprised 65 patients, mean age was 68 (±10) years, 89% were male, mean estimated GFR was 64 (±19) mL/min per 1.73 m(2), and 34% had New York Heart Association Class III symptoms. Renal plasma flow increased by 29% with serelaxin and 14% with placebo (13% relative increase with serelaxin; P=0.0386), whereas GFR changes did not differ significantly during 8 to 24 hours. Filtration fraction increased by 36% with serelaxin and 62% with placebo (16% relative decrease with serelaxin; P=0.0019) during 8 to 24 hours. Changes in systolic blood pressure were largely similar, and creatinine clearance did not differ between groups. Adverse event rates were similar with serelaxin (20.5%) and placebo (25.0%). CONCLUSIONS: In patients with chronic heart failure, serelaxin increased renal plasma flow and reduced the increase in filtration fraction compared with placebo, but did not affect GFR. These results suggest beneficial renal hemodynamic effects in patients with chronic heart failure. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01546532.
Authors: Victoria L Wolf; Taylor L Phillips; Erin B Taylor; Jennifer M Sasser; Michael J Ryan Journal: Am J Physiol Heart Circ Physiol Date: 2019-05-24 Impact factor: 4.733