Guidelines for the design and conduct of human clinical trials on ingestion-time differences – chronopharmacology and chronotherapy – of hypertension medications
Ramón C. Hermida, Michael H. Smolensky, Horia Bălan, Richard J. Castriotta, Juan J. Crespo, Yaron Dagan, Sherine El‐Toukhy, José R. Fernández, Garret A. FitzGerald, Akio Fujimura, Yong-Jian Geng, Ramon G. Hermida‐Ayala, António Pedro Machado, Luiz Menna‐Barreto, Artemio Mojón, Alfonso Otero, R. Daniel Rudic, Eva Schernhammer, Carsten Skarke, Tomoko Y. Steen, Martin E. Young, Xiaoyun Zhao
Abstract
procedure, not by inaccurate arithmetic averages. (vi) ABPM should be performed with validated and calibrated devices at least hourly throughout two or more consecutive 24 h periods (48 h in total) to achieve the highest reproducibility of mean wake-time, sleep-time and 48 h BP values plus the reliable classification of dipping status. (vii) Calculation of minimum required sample size in adherence with proper statistical methods must be provided. (viii) Hypertension chronopharmacology and chronotherapy trials should preferably be randomized double-blind, randomized open-label with blinded-endpoint, or crossover in design, the latter with sufficient washout period between tested treatment-time regimens.