Design considerations for hypertension chronotherapy trials: insights from experience and modelling

TY - JOUR

T1 - Design considerations for hypertension chronotherapy trials

T2 - insights from experience and modelling

AU - Walch, Olivia

AU - Rogers, Amy

AU - Huang, Yitong P

AU - Ruben, Marc D

AU - Dyar, Kenneth A

AU - Flynn, Robert W V

AU - Mackenzie, Isla S

AU - Manfredini, Roberto

AU - Cappuccio, Francesco P.

AU - Pigazzani, Filippo

N1 - © 2026. The Author(s).

PY - 2026/5/19

Y1 - 2026/5/19

N2 - Chronotherapy aims to maximise treatment efficacy while minimising side effects by scheduling treatment according to personal biological rhythms. In recent years, randomised clinical trials (RCTs) have been conducted to evaluate whether scheduled blood pressure interventions can improve patient outcomes. However, reports of time-of-day effects have attracted rebuttals and engendered methodological debate. A perfectly controlled chronotherapy trial (i.e., a trial that assesses the effect of assigning time of intervention) will never be feasible in the real world; yet some factors may be more critical to consider and control for than others. To advance the conversation about how best to evaluate the effects of antihypertensive chronotherapeutic interventions in RCTs, we discuss critical considerations for clinical trials of chronotherapy for hypertension and apply mathematical modelling to provide quantitative insights into the extent to which such factors may influence the detected effect size.

AB - Chronotherapy aims to maximise treatment efficacy while minimising side effects by scheduling treatment according to personal biological rhythms. In recent years, randomised clinical trials (RCTs) have been conducted to evaluate whether scheduled blood pressure interventions can improve patient outcomes. However, reports of time-of-day effects have attracted rebuttals and engendered methodological debate. A perfectly controlled chronotherapy trial (i.e., a trial that assesses the effect of assigning time of intervention) will never be feasible in the real world; yet some factors may be more critical to consider and control for than others. To advance the conversation about how best to evaluate the effects of antihypertensive chronotherapeutic interventions in RCTs, we discuss critical considerations for clinical trials of chronotherapy for hypertension and apply mathematical modelling to provide quantitative insights into the extent to which such factors may influence the detected effect size.

KW - Chronotherapy

KW - Chronotherapy Trial

KW - Chronotype

KW - Dosing time

KW - Hypertension

KW - Mathematical Modelling

KW - Trial Design

KW - Randomised Clinical Trials

U2 - 10.1186/s12916-026-04915-8

DO - 10.1186/s12916-026-04915-8

M3 - Article

C2 - 42157233

SN - 1741-7015

JO - BMC Medicine

JF - BMC Medicine

ER -