eprintid: 10041344
rev_number: 20
eprint_status: archive
userid: 608
dir: disk0/10/04/13/44
datestamp: 2018-01-15 15:07:49
lastmod: 2021-09-20 00:14:48
status_changed: 2018-01-15 15:07:49
type: article
metadata_visibility: show
creators_name: Judge, PK
creators_name: Haynes, R
creators_name: Herrington, WG
creators_name: Storey, BC
creators_name: Staplin, N
creators_name: Bethel, A
creators_name: Bowman, L
creators_name: Brunskill, N
creators_name: Cockwell, P
creators_name: Dayanandan, R
creators_name: Hill, M
creators_name: Kalra, PA
creators_name: McMurray, JJ
creators_name: Taal, M
creators_name: Wheeler, DC
creators_name: Landray, MJ
creators_name: Baigent, C
title: 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
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G93
keywords: Science & Technology, Life Sciences & Biomedicine, Transplantation, Urology & Nephrology, cardiovascular disease, chronic kidney disease, neprilysin, progression, PRESERVED EJECTION FRACTION, NEPRILYSIN INHIBITOR LCZ696, REQUIRING PROLONGED OBSERVATION, CONVERTING ENZYME-INHIBITION, CLINICAL-TRIALS, DIABETIC-NEPHROPATHY, DOUBLE-BLIND, FOLLOW-UP, RECEPTOR, FAILURE
note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/
abstract: 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.
date: 2016-09-17
date_type: published
publisher: OXFORD UNIV PRESS
official_url: https://doi.org/10.1093/ndt/gfw321
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1521035
doi: 10.1093/ndt/gfw321
lyricists_name: Wheeler, David
lyricists_id: DWHEE12
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Nephrology Dialysis Transplantation
volume: 32
number: 12
pagerange: 2043-2051
pages: 9
issn: 1460-2385
citation:        Judge, PK;    Haynes, R;    Herrington, WG;    Storey, BC;    Staplin, N;    Bethel, A;    Bowman, L;                                         ... Baigent, C; + view all <#>        Judge, PK;  Haynes, R;  Herrington, WG;  Storey, BC;  Staplin, N;  Bethel, A;  Bowman, L;  Brunskill, N;  Cockwell, P;  Dayanandan, R;  Hill, M;  Kalra, PA;  McMurray, JJ;  Taal, M;  Wheeler, DC;  Landray, MJ;  Baigent, C;   - view fewer <#>    (2016)    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.                   Nephrology Dialysis Transplantation , 32  (12)   pp. 2043-2051.    10.1093/ndt/gfw321 <https://doi.org/10.1093/ndt%2Fgfw321>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10041344/1/gfw321.pdf