{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:04:40Z","timestamp":1789646680191,"version":"4.0.0"},"reference-count":52,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Programme Hospitalier de Recherche Clinique","award":["PHRC 2020"],"award-info":[{"award-number":["PHRC 2020"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,10]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hypertension is the primary modifiable risk factor for cardiorenal complications of chronic kidney disease (CKD). It is well established that lowering blood pressure (BP) in patients with CKD reduces renal and cardiovascular complications. The guidelines advise starting the BP-lowering drug with ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB), but then there is no strong evidence to support the preferential use of any particular agent in controlling BP. Our hypothesis is that patients with CKD and uncontrolled hypertension are fluid overloaded and that the second line of treatment after an ACEi or an ARB should be a diuretic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a two-parallel group cluster randomised superiority phase 3 trial comparing a specific algorithm to lower BP in patients with moderate to severe CKD based on diuretics to standard of care. The primary endpoint is a composite time-to-event endpoint of (1) kidney failure with replacement therapy (KFRT), (2) estimated glomerular filtration rate decline \u226540%, (3) cardiovascular events (myocardial infarction, heart failure hospitalisation, stroke) and (4) all-cause mortality. Secondary endpoints include each component of the primary endpoint, systolic and diastolic BP at 3 months and 6 months post baseline then every 6 months, proportion of patients with controlled BP at 2 years, change from baseline in glomerular filtration rate and in proteinuria (g\/day) or proteinuria\/creatininuria (g\/g) at 3 months and 6 months post baseline then every 6 months, proportion of patients who used at least one diuretic, quality of life and safety. It is planned to include 720 patients in 40 centres.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study was approved by the Ethics Committee CPP Ile-de-France VII on 23 January 2023 (ref: 2022\u20135\u200901\u2009494-39-00). Study findings will be published in a peer-reviewed journal and presented at scientific conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05732727\">NCT05732727<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-122192","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:45:27Z","timestamp":1789645527000},"page":"e122192","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Intensification of blood pressure lowering therapeutics based on diuretics versus usual management for uncontrolled hypertension in patients with moderate to severe chronic kidney disease (THINK): protocol for an open label, two-parallel group, cluster randomised controlled, superiority, phase 3 trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct05732727","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-0246","authenticated-orcid":false,"given":"Floriane","family":"Le Vilain-Abraham","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Tours, Universit\u00e9 de Nantes, INSERM, SPHERE U1246, Tours, France"},{"name":"INSERM CIC1415, CHRU de Tours, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Halimi","sequence":"additional","affiliation":[{"name":"Unit\u00e9 INSERM 1327 Ischemia, Universit\u00e9 de Tours, Tours, France"},{"name":"Service de N\u00e9phrologie-Hypertension, Dialyse, Transplantation r\u00e9nale, CHU de Tours, Tours, France"},{"name":"F-CRIN INI-CRCT (Cardiovascular and 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