{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:25:07Z","timestamp":1789849507954,"version":"4.0.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":178,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2013neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients \u226518 years of age with an estimated glomerular filtration rate (eGFR) of \u226545 but &amp;lt;60 mL\/min\/1.73 m2 and urine albumin:creatinine ratio (uACR) &amp;gt;20 mg\/mmol or eGFR \u226520 but &amp;lt;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\u2013angiotensin 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfw321","type":"journal-article","created":{"date-parts":[[2016,9,19]],"date-time":"2016-09-19T20:48:45Z","timestamp":1474318125000},"page":"2043-2051","source":"Crossref","is-referenced-by-count":16,"title":["Randomized multicentre pilot study of sacubitril\/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III\u2014rationale, trial design and baseline data"],"prefix":"10.1093","volume":"32","author":[{"name":"UK HARP-III Collaborative 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