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Nephrol. Dial. Transplant.-2016--ndt-gfw321.pdf (534.6 kB)

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III-rationale, trial design and baseline data.

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posted on 2016-11-16, 11:15 authored by UK HARP-III Collaborative Group
Background Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. Methods UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor–neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin–angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. Results Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. Conclusions UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD.

Funding

UK HARP-III Collaborative Group acknowledges the support of the National Institute for Health Research, through the Clinical Research Network. The UK HARP-III trial was funded by a grant to the University of Oxford from Novartis (manufacturers of sacubitril/valsartan), but the study design, conduct, analysis and interpretation are the responsibility of the trial Steering Committee working with the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU). The University of Oxford is the regulatory sponsor for the trial. CTSU receives core funding from the UK Medical Research Council, British Heart Foundation and Cancer Research UK.

History

Citation

Nephrology Dialysis Transplantation (2016)

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

  • VoR (Version of Record)

Published in

Nephrology Dialysis Transplantation (2016)

Publisher

Oxford University Press (OUP) for European Renal Association - European Dialysis and Transplant Association (ERA-EDTA)

issn

0931-0509

eissn

1460-2385

Acceptance date

2016-07-24

Copyright date

2016

Available date

2016-11-16

Publisher version

http://ndt.oxfordjournals.org/content/early/2016/09/23/ndt.gfw321

Notes

Supplementary data are available online at http://ndt.oxfordjournals.org.

Language

en

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