Plain English Summary
Background and study aims
Statins reduce deaths from heart problems by 25%. Treatment is cheap, effective, safe, and randomised trials show that it is well-tolerated causing few side effects. However, half of all patients prescribed statins have stopped them one year later, primarily due to the perceived side-effects. One explanation for this is that people are experiencing adverse events that they misattribute to the statin and stop the medication.
We propose to harness individuals’ tendency to experiment with medication and create a coalition between doctor and patient that legitimizes and affirms experimentation in a way that will allow both to make inferences about the cause of adverse events that are more likely to be correct than currently is the case.
Who can participate?
Anyone living in the trial area over the age of 18, who is recommended by their GP to be on a statin can take part.
What does the study involve?
Participants will be placed into 3 groups. The open-label group will receive atorvastatin on and off in 4-week blocks. The closed-label group will receive atorvastatin and placebo in alternating 4-week blocks (but the capsules will look the same). The control group will receive treatment as usual. Participants will be supported to monitor adverse events and draw sound inferences about their cause using symptom diaries, 4-week on-off periods of medication use, and a review from their GP.
What are the possible benefits and risks of participating?
The benefits of taking part for participants is the opportunity to speak to the GP about the best way to reduce cholesterol and try a new approach to test whether the medicine (i.e. atorvastatin) is suitable to take long-term.
Taking part in the trial involves giving up some time to attend up to four study visits, and if randomised to one of the treatment groups, to complete a daily diary (taking about 5 minutes) for a week each month for the next six months. Taking part involves having a blood sample (requiring up to 8ml of blood). All blood tests come with a risk of bruising and pain.
Where is the study run from?
South Oxford Health Centre (UK)
When is the study starting and how long is it expected to run for?
May 2019 to April 2020 (updated 02/10/2019, previously: March 2020)
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
1. Jenny Brooks (public),
Jenny.brooks@phc.ox.ac.uk
2. Dr Kate Tudor (scientific)
kate.tudor@phc.ox.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Ms Jenny Brooks
ORCID ID
Contact details
Nuffield Department of Primary Care Health Sciences
University of Oxford Radcliffe
Observatory Quarter
Woodstock Road
Oxford
OX2 6GG
United Kingdom
01865289765
jenny.brooks@phc.ox.ac.uk
Type
Scientific
Additional contact
Dr Kate Tudor
ORCID ID
Contact details
Nuffield Department of Primary Care Health Sciences
University of Oxford Radcliffe Observatory Quar
Woodstock Road
Oxford
OX2 6GG
United Kingdom
01865289301
kate.tudor@phc.ox.ac.uk
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
41074
Study information
Scientific title
Tackling Statin Intolerance with N-of-1 trials in primary care (TASINI): testing the feasibility of a GP delivered behavioural intervention to increase statin adherence.
Acronym
TASINI
Study hypothesis
This is a feasibility trial. The principal question is whether a GP led intervention can improve adherence to statin medication (using an n-of-1-trial)
Ethics approval
Approved 22/02/2019, North of Scotland Research Ethics Committee (Summerfield House, 2 Eday Road, Aberdeen, AB15 6RE; Tel: +44 (0)1224 558458; Email: nosres@nhs.net), ref: 19/NS/0014
Study design
Individual randomised multi-centred trial
Primary study design
Interventional
Secondary study design
n-of-1 trial
Trial setting
GP practices
Trial type
Prevention
Patient information sheet
See additional files
Condition
Cardiovascular disease - preventing heart attack and stroke
Intervention
Participants will be randomised using an online randomization generator (http://www.randomization.com) to one of three arms: usual care, blinded n-of-1 experiment, and open-label n-of-1 experiment.
Participants in the open-label arm will receive atorvastatin 20mg on and off in 4 week blocks. Participants in the closed label arm will receive encapsulated atorvastatin 20mg and placebo in 4 week blocks (the order of statin/placebo will be randomised for the final 16 weeks of the study). Participants in the control group will receive usual care.
Participants will be supported to monitor adverse events and draw sound inferences about their cause using symptom diaries, 4-week on-off periods of medication use, and a review from their GP. We will then test the feasibility of this approach to assess whether GPs deliver the intervention as planned, whether patients engage with this, and whether it improves adherence to statins.
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
1. The proportion of invited patients who enrol in the trial.
2. The proportion of enrolled participants who accept GPs behavioural intervention.
3. Proportion of patients in the treatment conditions who decide to continue statin therapy compared to the proportion who decide to continue statin therapy in the usual care control arm.
Secondary outcome measures
1. Difference in the proportion of participants who decide to continue statin therapy in the ‘open-label’ (unblinded) treatment arm (i.e. alternating between medication and no treatment) compared to the proportion of participants who decide to continue statin therapy in the ‘closed-label’ (blinded) treatment arm (i.e. alternating between statin and placebo) and compared to the proportion of participants receiving usual care (control arm). Timepoint: 24 week follow up; decision to persist with statin therapy treatment full time.
2. Count of the number of adverse events by system class and preferred term level (according to MedDRA) in the blinded arm compared to the unblinded arm. Timepoint: 24 week follow up. Analysis of the symptom diary.
3. Count of the number of times that participant attributes side effects to statin medication in blinded arm compared to the unblinded arm. Timepoint: 24 week follow up; analysis of symptom diary.
4. The difference in mean pain severity (taken from Brief Pain Inventory) scores between statin therapy and placebo in the open label arm compared to the closed label arm. Timepoint: 24-week follow up; analysis of symptom diary.
5. The difference in mean pain interference scores (taken from the brief pain inventory) between statin therapy and placebo in the open-label arm compared to the closed label arm. Timepoint: 24-week follow up; analysis of symptom diary.
6. If applicable, focus groups with patients who declined to participate in the main study on the reasons for this decision. Timepoint: focus groups after recruitment period ends.
7. Compare participant BMQ scores before and after the intervention. Compare BMQ score changes between study groups. Timepoint: 24 week follow up.
Overall trial start date
01/05/2019
Overall trial end date
01/04/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Any patient that:
1. Is 18 years of age or older
2. Requiring statin therapy according to NICE guidelines and the GP thinks statins are indicated
3. Has previously been prescribed/recommended statin treatment
4. Has stopped/is considering stopping statin treatment/ or has not started statin treatment due to concerns about or experience of side-effects
5. Is willing and able to give informed consent for participation in the study and comply with study procedures
6. If on ezetimibe or another alternative to atrovstatin, willing to potentially cease said medication if randomised to one of the intervention arms
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
95
Total final enrolment
93
Participant exclusion criteria
Any patient that:
1. The GP thinks it is not indicated to recommence statins or the previous intolerance was severe enough to mean that recommencing statins may comprise a significant risk to health
2. Is unable to adhere to study procedures through illness or infirmity
3. Has any contraindications listed in the Summary of Product Characteristics (SmPC) for atorvastatin 20mg or placebo drug, including pregnancy
4. Is participating in any research project that may interact with the current study
Recruitment start date
01/06/2019
Recruitment end date
06/09/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
South Oxford Health Centre
Lake St
Oxford
OX1 4RP
United Kingdom
Sponsor information
Organisation
University of Oxford
Sponsor details
Joint Research Office
1st floor
Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
United Kingdom
01865616480
heather.house@admin.ox.ac.uk
Sponsor type
Research organisation
Website
Funders
Funder type
Government
Funder name
NIHR BRC Oxford Chronic Disease Cluster
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Funder name
NIHR CLAHRC Oxford
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal
IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication
Intention to publish date
31/03/2021
Participant level data
Other
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN11142694_PIS_Version 3.0_28Feb19.pdf Uploaded 27/06/2019