Plain English Summary
Background and study aims
Treatment in Morning versus Evening (TIME) is a study to compare the treatment for high blood pressure using hypertensive drugs given in the evening with the usual morning medication. This is done using an online system to record any side effects or changes due to the change in their medication. This automated system has worked well in our initial phase of this study with good patient response. Record-linkage to hospitalisations and deaths will be carried out and events monitored. Heart attack, stroke or death will be recorded and analysed to see if the timing of the medication has any impact.
Who can participate?
People who are already taking antihypertensive medication in usual care.
What does the study involve?
Participants take part by registering on a secure, study-specific website. Those who are eligible, are randomly allocated to continue taking medication at their usual time (usually morning) or to switch to taking medication in the evening. Subjects receive regular emails with simple links to record responses to track progress. Participants, people on their behalf, or GPs can record any side effects at any time online. Participants are followed up for 4 years.
What are the possible benefits and risks of participating?
Taking hypertensive medication in the evening may reduce the number of heart attack or stroke compared with usual morning dosing, and so is potentially of benefit to all hypertensive patients in the future. We do not think that there are any risks for patients taking part in the study.
Where is the study run from?
The study is sponsored by the University of Dundee, UK and run from the Medicines Monitoring Unit (MEMO) within this. The study is internet based and participants can be recruited from across the UK. They will be recruited from general practices, hospitals or by social media.
When is the study starting and how long is it expected to run for?
August 2011 to May 2019
Who is funding the study?
British Heart Foundation (UK)
Who is the main contact?
Ms Wendy Saywood
Ms Geraldine Mackle
Dept of Clinical Pharmacology
Division of Medicine and Therapeutics
Treatment In Morning versus Evening: an observational study
A trial comparing evening dosing of usual antihypertensive therapy with conventional morning dose is proposed.
East of Scotland Research Ethics Service (EoSRES) REC 1; 28/05/2011 (approval for the pilot study), 26/05/2014 (approval to move on to full study); ref. 11/AL/0309
Both; Observational; Design type: Not specified
Primary study design
Secondary study design
Patient information sheet
Topic: Primary Care, Cardiovascular disease; Subtopic: Other Primary Care, Cardiovascular (all Subtopics); Disease: All Diseases, Other
Timing of medication switch: Subjects already taking hypertensive medication in usual care will be identified from collaborating practices and within secondary care clinics. Subjects will be invited to participate in the study by registering on a study website. Registered subjects who meet the inclusion criteria will be randomised to continue taking medicine at their usual time (most often in the morning) or to switch to taking medication in the evening (or morning if evening is their usual time).
Primary outcome measures
The Anti Platelet Trialists' Collaboration: composite endpoint of non-fatal myocardial infarction, non-fatal stroke or vascular death.
Secondary outcome measures
1. Each component of the primary endpoint
2. Hospitalisation for non-fatal stroke
3. Hospitalisation for non-fatal MI
4. Vascular death
5. All-cause mortality
6. Hospitalisation or death from congestive heart failure.
1. Adherence to the evening dosing regimen vs morning (patient reported) with particular reference to patients taking diuretic therapy.
2. Patient reported and hospitalised adverse events in the morning versus evening groups will be compared. In particular falls and fractures will be recorded.
3. Home BP readings taken by a subset of patients will be compared between morning & evening dosing.
4. An additional proposed substudy is a telephone administered cognitive function assessment to compare patients on morning and evening dosing.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Both diagnosed and treated for hypertension (all forms) with at least one antihypertensive drug
2. Aged above 18 years
3. Have a valid email address
Target number of participants
Proposed following AM09: >20,000; Actual number recruited to date: 20,860 (AM09 (REC ref AM11): Approved 22/12/2015)
Participant exclusion criteria
1. Subjects who take twice daily antihypertensive therapy.
2. Subjects who work shift patterns that include a night shift.
3. Subjects who unwilling to consent to:
3.1. Follow up
3.2. Provide a surrogate to be contacted and/or
3.3. Give consent for their family practice to release follow up clinical data
3.4. To have their physical case records abstracted if required
3.5. To have their electronic case records searched and abstracted if required
3.6. To allow their consent from to be copied to authorities from whom the study team is requesting medical data
4. Those participating in another clinical trial or who have done in the last 3 months.
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Ninewells Hospital and Medical School
British Heart Foundation (BHF) (UK); Grant Codes: CS/14/1/30659
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26861939