ZILEBESIRAN AS ADD-ON THERAPY IN PATIENTS WITH HYPERTENSION INADEQUATELY CONTROLLED WITH A STANDARD ANTIHYPERTENSIVE MEDICATION: EFFICACY AND SAFETY RESULTS FROM THE KARDIA-2 STUDY
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Le résumé fourni par la source
Objective: Zilebesiran is an investigational RNA interference therapeutic that targets hepatic angiotensinogen, the most upstream precursor of the renin-angiotensin system. In the Phase 2 KARDIA-1 study, single subcutaneous (SC) doses of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to Months 3 and 6 versus placebo. The objective of KARDIA-2, a Phase 2 randomized, double-blind, placebo-controlled study, was to assess efficacy, safety, and pharmacodynamics of zilebesiran in combination with a standard-of-care antihypertensive medication class in patients with uncontrolled hypertension. Design and method: KARDIA-2 enrolled adults with mild-to-moderate hypertension who were untreated or receiving stable therapy with up to two antihypertensives. Patients entered a run-in period, where previous antihypertensives were discontinued, and were subsequently randomized to open-label, once-daily oral olmesartan 20 or 40 mg, amlodipine 5 mg, or indapamide 2.5 mg as background antihypertensive therapy. After at least 4 weeks of run-in, patients with 24-hr mean ambulatory SBP of 130–160 mmHg were randomized 1:1 to single-dose SC zilebesiran 600 mg or placebo as add-on therapy. Escape antihypertensives could be initiated after Month 3 if a patient's SBP met pre-specified escape criteria. However, assessments while patients were on or within two weeks of stopping any escape medication were excluded in analyses. The primary endpoint was change in 24-hr mean ambulatory SBP from baseline to Month 3, assessed as the least-square mean difference between zilebesiran and placebo. Key secondary endpoints were change from baseline to Month 3 in office SBP, time-adjusted change from baseline to Month 6 in 24-hr mean ambulatory and office SBP, and proportion of patients with 24-hr mean ambulatory SBP less than 130 mmHg and/or a reduction of at least 20 mmHg without escape medication at Month 6. Results: KARDIA-2 enrolled 672 patients and is currently ongoing. Primary, secondary, safety, and pharmacodynamic endpoints will be presented at the meeting. Conclusions: KARDIA-2 will provide insights into the potential benefit of adding zilebesiran to patients with hypertension inadequately controlled with standard-of-care antihypertensive monotherapy, building on efficacy and safety learnings from previous Phase 1 and 2 studies of this novel therapeutic strategy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- ZILEBESIRAN AS ADD-ON THERAPY IN PATIENTS WITH HYPERTENSION INADEQUATELY CONTROLLED WITH A STANDARD ANTIHYPERTENSIVE MEDICATION: EFFICACY AND SAFETY RESULTS FROM THE KARDIA-2 STUDY
- Date Crossref
- 01/05/2024
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Queen Mary University of London pays non établi dans la noticeUniversité ou école supérieure
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Queen Mary University of London, Barts Health NHS Trust et Vilnius University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.