Table 2:

Review of randomized control clinical trials investigating the use of aldosterone synthase inhibitors for the management of (a) hard to control blood pressure and (b) for the management of primary aldosteronism.

Study (year)	Aldosterone synthase inhibitor	Study design, number of patients	Patient population	Primary outcome	Treatment groups	Primary outcome result	Incidence of significant hyperkalemia
Calhoun et al (2011)⁴⁹	Osilodrostat	Phase II RCT, 524	Adults with stage 1 or 2 HTN, untreated or treated with ≥ 2 anti-hypertensives, eGFR > 60 mL/min	Change in trough mean DBP at 8 weeks compared to baseline	Placebo, osilodrostat (0.25 mg daily, 0.5 mg daily, 1 mg daily, 0.5 mg twice daily), eplerenone 50 mg twice daily	1 mg qd osilodrostat decreased DBP by −7.1 mmHg. Secondary outcome notable for statistically significant reduction in SBP compared to placebo for all doses of osilodrostat studied.	Incidence of K > 6: one in each osilodrostat group, hyperkalemia resolved on repeat lab draw.
BrigHTN (2023)⁵⁰	Baxdrostat	Phase II RCT, 275	Adults with resistant HTN: 3 anti-hypertensive medications with BP > 130/80. Patient with eGFR <45 mL/min were excluded	Change in mean systolic BP at 12-week visit compared to baseline	Placebo, baxdrostat (0.5 mg daily, 1 mg daily, 2 mg daily)	Decrease in SBP compared to placebo for 2 mg dose of −11 mmhg (CI −16.4 to −5.5), for 1 mg group −8.1 mmHg (−13.5 to −2.8)	6 cases of hyperkalemia requiring interruption or treatment, 4 patients were able to resume baxdrostat and complete trial with normokalaemia.
Target-HTN (2023)⁵³	Lorundrostat	Phase II RCT, 200	Adults with BP > 130/80 despite 4 weeks of ≥ 2 anti-hypertensives, eGFR > 60 mL/min	Change in systolic automated office BP at 8 weeks compared to baseline	Placebo, lorundrostat (12.5 mg daily, 12.5 mg twice daily, 25 mg twice daily, 50 mg daily, or 100 mg daily)	Decrease from placebo in least-squares mean BP of −11.9 mmHg (CI −14 .1 to −1.5) for 100 mg daily, −9.6 mmHg (−15.8 to −3.4) for 50 mg daily. Lower doses did not reach statistical significance.	6 patients had hyperkalemia above 6, managed through holding or decreasing dose of lorundrostat, complete the trial
BaxHTN (2025)⁵²	Baxdrostat	Phase III RCT, 794	Adults with uncontrolled HTN: BP > 140 despite treatment with 2 antihypertensives, resistant HTN: BP > 140 despite treatment with 3 antihypertensives with a diuretic	Change in seated systolic BP at 12-week visit compared to baseline	Placebo, badxrostat (1 mg daily, 2 mg daily)	Treatment difference from placebo was −8.7 mmHg (CI −11.5 to −5.8) for 1 mg, −9.8 mmHg (CI −12.6 to −7) for 2 mg.	Clinical intervention due to hyperkalemia: 7 of 264 for.1 mg, 21 of 266 patients with 2 mg, 0 of 264 in placebo.
Advance-HTN (2025)⁵¹	Lorundrostat	Phase IIb, 282	Adults with SBP 140–180 mmHg and DBP 65–110 or adults with DBP 90–110, taking 2–5 anti-hypertensives. Patient with eGFR <45 mL/min were excluded. Home anti-hypertensives were discontinued and were replaced with standard therapies.	Change in 24-hour average systolic BP at 12 weeks compared to baseline	Placebo, lorundrostat 50 mg daily (stable dose), lorundrostat 50 mg daily until 4 weeks after randomization, then increased to 100 mg daily if office SBP remained > 130 mmHg (dose-adjustment group)	Decrease compared to placebo of −7.9 mmHg (CI −13.3 to −2.6) for stable dose group, −6.5 mmHg (CI −11.8 to −1.2) for dose-adjustment group	Hyperkalemia leading to dose adjustment: 5 of 94 in stable dose group, 8 of 95 in dose-adjustment group, 0 of 95 in placebo group
LAUNCH-HTN (2025)⁵⁴	Lorundrostat	Phase III, 1083	Adults with SBP 140–180 mmHg and DBP 65–110 or adults with DBP 90–110, taking 2–5 anti-hypertensives. Patient with eGFR <45 mL/min were excluded. Home anti-hypertensives were discontinued and were replaced with standard therapies.	Change in office SBP at 6 weeks compared to baseline	Placebo, lorundrostat 50 mg once daily, lorundrostat 50 mg once daily until 6 weeks, then 100 mg if SBP > 130 mmHg	Mean group difference between placebo and stable 50 mg dose of −9.1 mmHg (CI −13.3 to −4.9)	Dose reduction, interruption, or discontinuation due to hyperkalemia: 11 of 538 in standard dose group 7 of 270 in higher dose group, 1 of 270 in placebo group
Mulatero et al (2024)⁵⁵	Dexfadrostat	Phase IIa, 35	Adults with primary aldosteronism and office SBP of 145–190 mmHg	Change in aldosterone to renin ratio and mean 24 hour ambulatory SBP at 8 weeks compared to baseline	Dexfadrostat (4 mg, 8 mg, 12 m daily)	Decrease in least-squares mean 24 hour ambulatory SBP decreased by 10.7 mmHg (CI −13.6 to −7.9)	No instances of hyperkalemia noted during treatment period.
SPARK (2025)⁵⁶	Baxdrostat	Phase IIa, 15	Adults with hypertension and primary aldosteronism	Change in office systolic BP at 12 weeks compared to baseline	Baxdrostat (2 mg daily for 2 weeks, then increased to 4 mg or 8 mg as tolerated)	Mean reduction in SBP by −24.9 mmHg (CI −19 to −30.8)	No patients had hyperkalemia during the primary study period of 12 weeks.