Treatment in morning versus evening study
| ISRCTN | ISRCTN18157641 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18157641 |
| Secondary identifying numbers | 17071 |
- Submission date
- 21/08/2014
- Registration date
- 20/10/2014
- Last edited
- 13/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
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. Participants 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. There are no known 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 July 2022
Who is funding the study?
British Heart Foundation (UK)
Who is the main contact?
Ms Wendy Saywood
wendys@memo.dundee.ac.uk
Contact information
Scientific
Medicine Monitoring Unit (MEMO)
University of Dundee
Dundee
DD2 1GZ
United Kingdom
| Phone | +44(0)1382 383437 |
|---|---|
| r.y.barr@dundee.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | https://www.timestudy.co.uk/info_sheets/TIME%20STUDY%20-%20Patient%20Information%20Sheet.pdf |
| Scientific title | Treatment In Morning versus Evening: an observational study |
| Study acronym | TIME |
| Study hypothesis | A trial comparing evening dosing of usual antihypertensive therapy with conventional morning dose is proposed. |
| Ethics approval(s) | 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 |
| Condition | Topic: Primary Care, Cardiovascular disease; Subtopic: Other Primary Care, Cardiovascular (all Subtopics); Disease: All Diseases, Other |
| Intervention | 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). |
| Intervention type | Other |
| Primary outcome measure | 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 study start date | 03/08/2011 |
| Overall study end date | 27/07/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Proposed following AM09: >20,000; Actual number recruited to date: 20,860 (AM09 (REC ref AM11): Approved 22/12/2015) |
| Total final enrolment | 21104 |
| 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 |
| 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 | 07/12/2011 |
| Recruitment end date | 05/06/2018 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
DD1 9SY
United Kingdom
Sponsor information
Hospital/treatment centre
R&D Office
Level 9
Ninewells Hospital and Medical School
Ninewells Avenue
Dundee
DD1 9SY
Scotland
United Kingdom
"ROR" |
https://ror.org/000ywep40 |
|---|
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 12/10/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Presentation of results at European Society of Cardiology (ESC) Congress (Barcelona 26-29 August 2022) and ISH (Kyoto, 12-16 October 2022) Substudies will be published separately. Results have been shared by email with all participants and participating research networks (see attached lay summary). |
| IPD sharing plan | Access to a de-identified participant dataset and data dictionary is available upon reasonable request to researchers who provide a methodologically sound proposal, with no prespecified restrictions on data use. Any such requests should be sent to the corresponding author for consideration by the trial steering committee. There might be restrictions on sharing data derived from record-linkage to NHS datasets. A period of 18 months after publication of the main study results should elapse before requests are made, to allow the authors to publish substudies and further analyses. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 09/02/2016 | Yes | No | |
| Protocol article | substudy protocol | 07/06/2018 | Yes | No | |
| Other publications | analysis of recruitment, retention and follow-up rates | 01/12/2017 | 18/03/2020 | Yes | No |
| Statistical Analysis Plan | version 1 | 29/06/2022 | 29/07/2022 | No | No |
| Plain English results | version 1.0 | 11/10/2022 | 13/10/2022 | No | Yes |
| Results article | 11/10/2022 | 13/10/2022 | Yes | No |
Additional files
Editorial Notes
13/10/2022: The following changes were made to the trial record:
1. The plain English results was uploaded as an additional file.
2. Publication reference added.
3. The recruitment start date was changed from 03/08/2011 to 07/12/2011.
4. The recruitment end date was changed from 04/07/2016 to 05/06/2018.
5. The publication and dissemination plan was updated.
6. The participant level data sharing plan was added.
7. The intention to publish date was changed from 31/12/2022 to 12/10/2022.
29/07/2022: The following changes were made to the trial record:
1. The statistical analysis plan was uploaded as an additional file.
2. The overall end date was changed from 30/06/2022 to 27/07/2022.
3. The publication and dissemination plan, was updated.
4. The plain English summary was updated to reflect these changes.
13/12/2021: The following changes were made to the trial record:
1. The overall end date was changed from 31/12/2021 to 30/06/2022.
2. The trial website was added.
3. The plain English summary was updated to reflect these changes.
16/04/2020: The following changes have been made:
1. The overall trial end date has been changed from 03/04/2021 to 31/12/2021.
2. The EudraCT number and ClinicalTrials.gov number have been added.
3. The total final enrolment number has been added.
4. The publication and dissemination plan has been added.
5. The intention to publish date has been added.
6. The participant level data statement has been added.
7. The scientific contact has been updated.
8. The plain English summary has been updated to reflect the changes above.
18/03/2020: The following changes have been made:
1. Publication reference added.
2. The overall trial end date has been changed from 31/05/2019 to 03/04/2021.
11/06/2018: Publication reference added.
23/08/2016: The following changes were made to the trial record:
1. The overall trial end date was changed from 04/07/2016 to 31/05/2019.
2. The target number of participants was changed from 'Planned Sample Size: 10269; UK Sample Size: 10269' to 'Proposed following AM09: >20,000; Actual number recruited to date: 20,860 (AM09 (REC ref AM11): Approved 22/12/2015)'.
10/02/2016: Publication reference added.
