{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:48:26Z","timestamp":1787064506587,"version":"build-2736575974"},"reference-count":26,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000035","name":"Institute of Nutrition, Metabolism and Diabetes","doi-asserted-by":"publisher","award":["PJT-195982"],"award-info":[{"award-number":["PJT-195982"]}],"id":[{"id":"10.13039\/501100000035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,12,5]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Primary aldosteronism (PA) is a highly prevalent but underdiagnosed cause of hypertension, characterised by renin-independent aldosterone production. PA is associated with a higher incidence of cardiovascular and kidney complications, independent of blood pressure. Although mineralocorticoid receptor antagonists (MRAs) are the standard treatment when surgical adrenalectomy is not clinically indicated or possible, response is typically monitored using indirect clinical markers such as blood pressure and potassium. Emerging evidence suggests that achieving renin unsuppression may result in better outcomes, yet this hypothesis has not been tested in a randomised controlled trial. The objective of this trial is to evaluate whether a renin-guided MRA titration strategy improves biochemical efficacy compared with standard titration in patients with PA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a multicentre, open-label, pragmatic randomised controlled trial in four academic centres in Canada. 58 adults with confirmed PA, suppressed renin at baseline, and an indication for long-term MRA therapy will be enrolled. Key exclusion criteria include prior MRA use, estimated glomerular filtration rate &lt;30\u2009mL\/min\/1.73\u2009m\u00b2, potassium levels &gt;4.8\u2009mmol\/L and pregnancy. The primary endpoint is the proportion of participants with unsuppressed renin at 12 months. Secondary outcomes include blood pressure, left ventricular mass, kidney function, MRA dose, quality of life and various safety outcomes. Participants will be randomised 1:1 to a renin-guided titration strategy or standard care. In the intervention arm, MRAs will be titrated to achieve unsuppressed renin (&gt;10\u2009ng\/L, &gt;15\u2009mIU\/L or &gt;1.0\u2009ng\/mL\/hour). The control arm follows usual clinical practice, without serial renin measurements during dose titration. All participants will be followed for 12 months, with visits at 1, 3, 6, 9 and 12 months. Analysis will follow the intention-to-treat principle and use Fisher\u2019s exact test for proportions, mixed-effects models for continuous outcomes and Kaplan-Meier estimates for time-to-event data. The trial is powered to detect a 42% absolute difference in the primary outcome (40% in the control groups vs 82% in the experimental group; alpha 0.05, 80% power, 15% loss to follow-up). This trial will be the first to prospectively assess the biochemical efficacy of a renin-guided MRA titration strategy in PA. If successful, the next phase will be to assess the efficacy of this strategy on important surrogate outcomes and patient-reported outcome measures.<\/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 Research and Ethics Board of the Centre int\u00e9gr\u00e9 universitaire de sant\u00e9 et de services sociaux du Nord-de-l\u2019\u00cele-de-Montr\u00e9al (project number 2024-2727). All the participating sites have received the ethics approval. The findings will be disseminated through national and international presentations and peer-reviewed publications.<\/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=\"NCT06108427\">NCT06108427<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-111167","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T11:50:53Z","timestamp":1766145053000},"page":"e111167","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Renin-guided therapy with mineralocorticoid receptor antagonists in primary aldosteronism: feasibility study (RETAME-PA) \u2014 a clinical research protocol for a randomised controlled trial"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06108427","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Amel","family":"Merabtine","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7536-8497","authenticated-orcid":false,"given":"Alexander A","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A","family":"Kline","sequence":"additional","affiliation":[{"name":"University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Dubrofsky","sequence":"additional","affiliation":[{"name":"Women\u2019s College Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-3531","authenticated-orcid":false,"given":"Gregory L","family":"Hundemer","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ottawa Hospital General Campus, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-3735","authenticated-orcid":false,"given":"R\u00e9mi","family":"Goupil","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"},{"name":"Department of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"},{"name":"H\u00f4pital du Sacr\u00e9-Coeur de Montr\u00e9al, Montreal, 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