Journal of Clinical Trials
Open Access
ISSN: 2167-0870
ISSN: 2167-0870
David A Rorie, Amy Rogers, Isla S Mackenzie, Evelyn Findlay, Thomas M MacDonald, Ian Ford, David J Webb, Bryan Williams, Morris Brown and Neil Poulter
Aims: The Treatment in Morning versus Evening (TIME) pilot study sought to establish the feasibility of an onlineonly study detecting whether evening dosing of antihypertensives is more cardio protective than morning dosing. Methods: The TIME study uses a prospective, randomised, open-label, blinded end-point (PROBE) design. In response to various forms of advertising, patients from primary and secondary care, and databases of patients who had previously consented to being contacted about research in the UK, enrolled on the study website (www.timestudy.co.uk). Furthermore, 1,794 hypertensive subjects were written to in three primary care practices as a form of targeted advertising. Participants had to be over 18, prescribed at least one hypertensive drug and have a valid email address. Subjects self-registered, consented, and entered demographics and drug treatments online, before being randomised to taking their antihypertensive therapy in the morning or evening. Automated email followup was used to track patient reported cardiovascular outcomes for the year-long pilot study. Result: 355 participants were randomised and followed up for ≥ 12 months. During this period, 14 participants withdrew from the randomised time of treatment. 59 patients were randomised from 3 practices which wrote to patients publicising the study, giving a rate of 33 randomised per 1,000 patients written to. The 10-year ASSIGN cardiovascular risk of the randomised participants varied by age; 21% for all ages (n=355), 25% for >55 yrs (n=269), 27% for >60 yrs (n=227) and 30% for >65 yrs (n=150). Based on participant cardiovascular risk during the pilot, a full trial with 80% power to detect a 20% improved outcome of nocturnal dosing would require 631 events to occur. Conclusion: The TIME study pilot achieved recruitment efficiently. Based on the pilot data, the TIME study appears viable and has been funded by the British Heart Foundation to recruit over 10,269 subjects and to follow them up for 4 years.