Abstract 4366848: Advance-HTN Trial Participant Characteristics Associated with a Failure to be Randomized

Abstract

Background: Placebo or sham-controlled clinical trials of new hypertension therapies often use run-in periods to assess participant adherence to background antihypertensive (AHT) therapy, assess participant response to a standardized AHT regimen and/or measure out of office blood pressure (BP) prior to randomization to ensure true uncontrolled hypertension. When these factors are assessed a large proportion of participants are excluded prior to randomization which can negatively impact a trial’s ability to enroll in an efficient manner. The Advance-HTN trial demonstrated the BP lowering efficacy of lorundrostat compared with placebo. Participants taking 2 to 5 AHT medications were enrolled and then switched to a standardized AHT regimen for a 3-week run-in period. The standardized regimen included olmesartan, a diuretic (hydrochlorothiazide or indapamide) and in certain cases amlodipine (if participant was taking ≥3 medications at enrollment). Participants were subsequently randomized if BP was uncontrolled when 24-hour ambulatory BP was measured while taking the standardized regimen. Objective: This post hoc analysis aims to understand which Advance-HTN participant characteristics were associated with a failure to be randomized among participants that were enrolled and participated in the standardized AHT regimen run-in period. Methods: Multivariable logistic regression was performed comparing participants who took part in the run-in period and failed to be randomized with those participants that were successfully randomized. Candidate predictors included participant demographics, labs and medication use (Table). Results: Of the 926 participants who started the standardized AHT regimen 285 proceeded to randomization. In the multivariable model, diabetes was associated with lower odds of failure to be randomized (OR: 0.61, 95% CI: 0.45-0.81, p < 0.001). Similarly, higher office systolic BP at screening was associated with lower odds of failure to be randomized (OR: 0.83 per 10 mmHg increase, 95% CI: 0.74-0.93, p < 0.001). In contrast, use of indapamide in the standardized AHT regimen was associated with greater odds of failing to be randomized (OR: 1.39, 95% CI: 1.03-1.87, p = 0.03). Conclusion: Advance-HTN participant characteristics associated with a failure to be randomized were identified. These data may inform future hypertension trial design including participant selection strategies to maximize enrollment of patients with true uncontrolled hypertension