Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial
Michel Azizi, Jenifer M. Brown, Jamie P. Dwyer, John M Flack, Erica S W Jones, Raisa Kurlyandskaya, Hongjian Li, Filip Birve, Aina S. Lihn, Shira Perl, Markus P. SCHLAICH, Hirotaka Shibata, Ji-Guang Wang, Bryan Williams, Cesar Zaidman, Sonia Sassone, Miguel Cuenca, Diego Arakaki, Mariano I. Chahin, María Andrea Steinacher, Fredy Ferre Pacora, Juan Loureyro, Jun Yang, Markus P. SCHLAICH, Tine De Backer, Hans T Kindt, P. Delmotte, Blagovest Stoimenov, Kiril Dzhomanov, Krassimir Cvetkov, Dimitar Raev, Stefan Naydenov, Shivinder Jolly, John Vyselaar, Luis Noronha, Daniel Gaudet, A. Shekhar Pandey, Jennifer Ringrose, Yves Robitaille, Jiri Vesely, Jiri Krupicka, Ladislav Busak, Jitka Pruchova, Wolfgang Jungmair, Sebastian Cremer, Markus van der Giet, Stephan H. Schirmer, Spasija Parizova, Michael Doumas, George Stergiou, Konstantinos Tsioufis, Zoltán Miklós Járai, András Vorobcsuk, Tibor Kiss, Gizella Pap, Andras Csaba Nagy, Attila Farkas, Desmond Samuel, Mohd Faiz Faizul Fauzi, Mohamad Muslim Jamian, Louie Tirador, Gabriel Jocson, Marek Rajzer, Andrzej Januszewicz, Andrzej Tykarski, Michał Hoffmann, Jan Zbigniew Peruga, Edyta Zbroch, Piotr Sobieraj, Abdulmajid Mukhtar, Talal Aljabbary, Lubomir Antalik, Ján Fedačko, Peter Fulop, Lesley Burgess, Gulam Latiff, Julián Segura de la Morena, José Antonio García Donaire, Miguel Camafort Babkowski, Alejandro de la Sierra, Javier Sobrino Martínez, Anna Oliveras Serrano, Fernando Martinez, Manuel Gorostidi Pérez, Francisco Fuentes Jimenez, Chern‐En Chiang, Kang-Ling Wang, Yen-Wen Wu, I-Chang Hsieh, Praew Kotruchin, Yongkasem Vorasettakarnkij, Weranuj Roubsanthisuk, Prin Vathesatogkit, Krit Leemasawat, Hilmi Erdem Sumbul, Özge Turgay Yıldırım, ÇAĞRI YAYLA, Ozkan Gungor, İsmail Koçyiğit, Auditi Naziat
Abstract
BACKGROUND: Aldosterone dysregulation is an important contributor in the pathogenesis of hard-to-control hypertension. We aimed to assess the effect of baxdrostat, a selective aldosterone synthase inhibitor, on ambulatory blood pressure in patients with resistant hypertension. METHODS: The Bax24 international, phase 3, randomised, double-blind, placebo-controlled trial recruited adults (aged ≥18 years) with seated systolic blood pressure (SBP) ≥140 mm Hg and <170 mm Hg, despite receiving three or more antihypertensive medications, including a diuretic, from 79 clinical sites (primary, secondary, and tertiary centres, in addition to research centres) in 22 countries. Following a 2-week placebo run-in period, patients with 24 h ambulatory SBP ≥130 mm Hg were randomly assigned (1:1) to receive 2 mg baxdrostat or placebo orally once daily for 12 weeks, in addition to background therapy (stratified by baseline ambulatory SBP <140 mm Hg or ≥140 mm Hg). Investigators, patients, and trial staff were masked to treatment assignment. The primary endpoint was change in 24 h ambulatory SBP from baseline to week 12, assessed by analysis of covariance in patients administered at least one dose of study medication with valid ambulatory SBP measurement at baseline and week 12. Missing or invalid ambulatory SBP measurements were not imputed. The safety analysis included all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT06168409, and is complete. FINDINGS: Between March 1, 2024, and April 16, 2025, 854 patients were screened, 636 were excluded (437 before the placebo run-in and 199 during the placebo run-in) and 217 were randomly assigned to and received baxdrostat (n=108) or placebo (n=109). 140 patients (65%) were male, 77 (35%) patients were female, and 170 patients (78%) were White. The median age was 60·0 years (IQR 51·0-68·0). At 12 weeks, the change from baseline in the least-squares mean 24 h ambulatory SBP was -16·6 mm Hg (95% CI -18·8 to -14·3) in the baxdrostat group (n=89) and -2·6 mm Hg (-4·7 to -0·4) in the placebo group (n=95); the estimated placebo-corrected difference was -14·0 mm Hg (-17·2 to -10·8; p<0·0001). Adverse events occurred in 56 (52%) of 108 patients in the baxdrostat group and 40 (37%) of 109 patients in the placebo group. A confirmed potassium level of more than 6 mmol/L occurred in three (3%) of the 108 baxdrostat recipients and in none of the placebo recipients. INTERPRETATION: Baxdrostat significantly reduced 24 h ambulatory SBP versus placebo in patients with resistant hypertension, providing further evidence of the potential of aldosterone synthase inhibition for treatment of hard-to-control hypertension. FUNDING: AstraZeneca.