Ischemic StrokeSAFEST-cohNCT06785740
Statins in Frail Older Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study
An observational study of Ischemic Stroke and TIA, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 4 sites in Netherlands.
Trial summary
Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST-cohort, the investigators will assess the impact of continuing versus discontinuing a statin in frail individuals aged 70 and above with a recent ischemic stroke or… Read more about this study
- Who is it for?
- Ages 70 to 120 years
- Conditions the study is for
- Ischemic Stroke, TIA
- What is being tested?
- Statin
- How many people
- 300 participants
- Where
- 4 sitesNetherlands
- Study dates
- 1 Nov 2024to Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 to 120 years
- All sexes
- No healthy volunteers
- Older adult
Study population: frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA)
Who may be able to join
- age = 70 years or older at the time of ischemic stroke or TIA;
- inclusion within 6 weeks after diagnosis of ischemic stroke or TIA;
- already using statin therapy at the time of the index event;
- frailty as defined by a pre-event score of 4-7 and/or post-event score of 6-7 on the validated Clinical Frailty Scale.
Who cannot join
- Previous serious adverse drug reactions (defined as an adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisa-tion, results in persistent or significant disability or incapacity, or is a birth defect32) to statins or other contraindications to statin use.
- Very severe frailty or very limited life expectancy (< 6 months) as defined by a score >= 8 points on the validated Clinical Frailty Scale.
- Inability to communicate in Dutch.
- Inability to respond to questions, either independently or with the assistance of a proxy.
- Inability or unwillingness to provide written informed consent, either independently or with the assistance of a proxy.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands4 sites, 4 recruiting
- Recruiting
Flevoziekenhuis
Almere Stad
Elizabeth Osei, MD, PHD, 0031368688720, losei@flevoziekenhuis.nl
- Recruiting
Amsterdam UMC, location AMC
Amsterdam
Susanna Prins, MD, 0031205669111, s.r.prins@amsterdamumc.nl
- Recruiting
Catharina Ziekenhuis
Eindhoven
Rob Gons, MD, PHD, 031402399426, rob.gons@catharinaziekenhuis.nl
- Recruiting
Isala Klinieken
Zwolle
Wilmar Jolink, MD, PHD, 0031886242461, w.m.t.jolink@isala.nl
About this study
Official title: StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study
Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST-cohort, the investigators will assess the impact of continuing versus discontinuing a statin in frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA) on their health-related quality of life and MACE free survival during a two-year follow-up period.
Read the detailed description
The stroke incidence strongly increases with age.Many of the older individuals that suffered a stroke will have to live with stroke sequelae and will need lifelong care, either at home or in a nursing facility.
Hence, secondary prevention strategies are of the highest importance. Statins are used for the prevention of subsequent cardiovascular events in ischemic stroke and TIA patients. The efficacy of statin therapy has been firmly established in middle-aged stroke patients. However, despite the high prevalence of stroke in older people, the evidence for the efficacy of statin therapy in older individuals that suffered an ischemic stroke or TIA is sparse. This primarily arises from the underrepresentation of older patients in statin trials.
In a recent meta-analysis, it was found that in people aged 70 and above, statin use lowered the annual incidence of major vascular events with approximately one percent. However, the trials in this meta-analysis mostly included fit, non-frail older adults.
Frailty is a geriatric condition characterized by an increased vulnerability to external stressors, linked to adverse outcomes, including premature mortality. A considerable proportion of the older population is frail. However, since trials that include older individuals often focus on fit, non-frail older adults, there is currently no evidence for the most effective treatment strategy in the frail older group.
While it might be tempting to extrapolate the benefits of statin therapy from younger patients to frail older patients, it is vital to acknowledge the considerable disparities between these groups. Firstly, frail older stroke survivors may not have a life-expectancy longer than the time to benefit. Secondly, due to the high percentage of polypharmacy in frail older people, this patient group has a higher risk for the occurrence of drug-drug interactions and adverse effects, which have the ability to significantly affect the quality of life.
The limited body of evidence regarding the effectiveness of statins in the older population, combined with their higher susceptibility to side effects and drug interactions, results in uncertainty for patients as well as for doctors and policymakers when deciding how to treat this patient group.This uncertainty is clearly reflected in the two Dutch guidelines ("Herseninfarct en Hersenbloeding" and "Cardiovascular Risk Management (CVRM)" respectively), providing conflicting advice on optimal statin treatment in older patients.
The investigators hypothesize that in frail older patients with a recent ischemic stroke or TIA, discontinuing statins will increase health-related quality of life (HrQoL) without a substantial decrease in Major Adverse Cardiovascular Events (MACE) free survival, which includes cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke.
In this prospective cohort study, no intervention will be implemented. Participants will be followed for two years (and for the patients included in the first years of the inclusion period - three). During this time, data is collected including questionnaires on quality of life, occurrence of MACE or falls, and possible changes in statin treatment.
- Conditions
- Ischemic Stroke, TIA
- Being tested
- Statin
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StatinDrug
Also called atorvastatin, rosuvastatin, pravastatin, simvastatin, fluvastatin
Statin use
| Study group | Role | What they receive |
|---|---|---|
| Statin continued | Patients in which the statin was continued after the index event Receives: Drug: Statin | |
| Statin discontinued | Patients in which the statin was discontinued after the index event |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health-Related Quality of Life (HrQoL)
This will be measured using the PROMIS-10 scale scores (ranging from 0 to 100, with higher scores indicating better health), including global mental health and global physical health subscales. Measurements at 3, 6, 12, 18, 24 (and 36) months.
months.
Measured: 3, 6, 12, 18, 24 (and 36) months
Major Adverse Cardiovascular Events (MACE) free survival
Classical 3-point MACE (cardiovascular death, nonfatal MI, or nonfatal stroke) and non-cardiovascular death.
Measurements at 3, 6, 12, 18, 24 (and 36) months.
Measured: 3, 6, 12, 18, 24 (and 36) months
Secondary outcomes (7)
Functional outcome
This will be assessed using the modified Rankin Scale (mRS), with scores ranging from 0 to 6 (lower scores indicating better function).
Measured: 3, 6, 12, 18, 24 months
Cognition
This will be measured using the Montreal Cognitive Assessment (MoCA) with scores ranging from 0 (worst) to 30 (best) or the Telephone version of the MoCA (TMoCA) with scores ranging from 0 (worst) to 22 (best)
Measured: 3, 6, 12, 18, 24 months
Number of falls
Falls, measured using the falls calender. Participant returns the fall calender every 3 months.
Measured: 3, 6, 12, 18, 24 months
Time to first fall
Falls, measured using the falls calender. Participant returns the fall calender every 3 months.
Measured: 3, 6, 12, 18, 24 months
General quality of life using the EQ-5D-5L
General QoL, measured by the EuroQol Questionnaire (EQ-5D-5L), with scores ranging from 0-100, the higher, the better.
Measured: 3, 6, 12, 18, 24 months
Societal costs
Societal costs measured by The Older Persons and Informal Caregivers Survey - Minimum Data Set (TOPICS-MDS) (questions 23 - 37)
Measured: 3, 6, 12, 18, 24 months
Cardiovascular risk status
This will be assessed by collecting vital signs (height, weight, and blood pressure) and lipid levels. The exact way how to combine these factors into one risk status will be determined.
Measured: 3, 6, 12, 18, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2025
- Study start1 Nov 2024
- Primary completionSep 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- VU University of Amsterdam
- Responsible party
- Principal investigator, Prof. dr. Nathalie van der Velde, Amsterdam UMC, location AMC
- Investigators
- Renske van den Berg-Vos, Prof. dr., Principal investigator, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsNathalie van der Velde, Prof. dr., Principal investigator, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06785740
- Sponsor's protocol ID
- 2024.0202
- Acronym
- SAFEST-coh
- Status last verified
- Jan 2025
- First submitted
- 3 Jul 2024
- Last updated
- 21 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The SAFEST database can be requested by other researchers. These requests will be reviewed according the requirements for sharing SAFEST data.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT06785740
- Acronym / sponsor ID
- SAFEST-coh / 2024.0202
- Conditions
- Ischemic Stroke, TIA
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- VU University of Amsterdam
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 21 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST-cohort, the investigators will assess the impact of continuing versus discontinuing a statin in frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA) on their health-related quality of life and MACE free survival during a two-year follow-up period.
Detailed description
The stroke incidence strongly increases with age.Many of the older individuals that suffered a stroke will have to live with stroke sequelae and will need lifelong care, either at home or in a nursing facility.
Hence, secondary prevention strategies are of the highest importance. Statins are used for the prevention of subsequent cardiovascular events in ischemic stroke and TIA patients. The efficacy of statin therapy has been firmly established in middle-aged stroke patients. However, despite the high prevalence of stroke in older people, the evidence for the efficacy of statin therapy in older individuals that suffered an ischemic stroke or TIA is sparse. This primarily arises from the underrepresentation of older patients in statin trials.
In a recent meta-analysis, it was found that in people aged 70 and above, statin use lowered the annual incidence of major vascular events with approximately one percent. However, the trials in this meta-analysis mostly included fit, non-frail older adults.
Frailty is a geriatric condition characterized by an increased vulnerability to external stressors, linked to adverse outcomes, including premature mortality. A considerable proportion of the older population is frail. However, since trials that include older individuals often focus on fit, non-frail older adults, there is currently no evidence for the most effective treatment strategy in the frail older group.
While it might be tempting to extrapolate the benefits of statin therapy from younger patients to frail older patients, it is vital to acknowledge the considerable disparities between these groups. Firstly, frail older stroke survivors may not have a life-expectancy longer than the time to benefit. Secondly, due to the high percentage of polypharmacy in frail older people, this patient group has a higher risk for the occurrence of drug-drug interactions and adverse effects, which have the ability to significantly affect the quality of life.
The limited body of evidence regarding the effectiveness of statins in the older population, combined with their higher susceptibility to side effects and drug interactions, results in uncertainty for patients as well as for doctors and policymakers when deciding how to treat this patient group.This uncertainty is clearly reflected in the two Dutch guidelines ("Herseninfarct en Hersenbloeding" and "Cardiovascular Risk Management (CVRM)" respectively), providing conflicting advice on optimal statin treatment in older patients.
The investigators hypothesize that in frail older patients with a recent ischemic stroke or TIA, discontinuing statins will increase health-related quality of life (HrQoL) without a substantial decrease in Major Adverse Cardiovascular Events (MACE) free survival, which includes cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke.
In this prospective cohort study, no intervention will be implemented. Participants will be followed for two years (and for the patients included in the first years of the inclusion period - three). During this time, data is collected including questionnaires on quality of life, occurrence of MACE or falls, and possible changes in statin treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Statin continued | – | Drug: StatinPatients in which the statin was continued after the index event |
| Statin discontinued | – | –Patients in which the statin was discontinued after the index event |
Who may qualify
- Ages
- 70 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- frail individuals aged 70 and above with a recent ischemic stroke or transient ischemic attack (TIA)
Key inclusion criteria (4 listed)
- age = 70 years or older at the time of ischemic stroke or TIA;
- inclusion within 6 weeks after diagnosis of ischemic stroke or TIA;
- already using statin therapy at the time of the index event;
- frailty as defined by a pre-event score of 4-7 and/or post-event score of 6-7 on the validated Clinical Frailty Scale.
Key exclusion criteria (5 listed)
- Previous serious adverse drug reactions (defined as an adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisa-tion, results in persistent or significant disability or incapacity, or is a birth defect32) to statins or other contraindications to statin use.
- Very severe frailty or very limited life expectancy (< 6 months) as defined by a score >= 8 points on the validated Clinical Frailty Scale.
- Inability to communicate in Dutch.
- Inability to respond to questions, either independently or with the assistance of a proxy.
- Inability or unwillingness to provide written informed consent, either independently or with the assistance of a proxy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| StatinAlso: atorvastatin, rosuvastatin, pravastatin, simvastatin, fluvastatinStatin use | Drug | Statin continued |
Primary outcome
Health-Related Quality of Life (HrQoL)
Time frame: 3, 6, 12, 18, 24 (and 36) months
This will be measured using the PROMIS-10 scale scores (ranging from 0 to 100, with higher scores indicating better health), including global mental health and global physical health subscales. Measurements at 3, 6, 12, 18, 24 (and 36) months. months.
Major Adverse Cardiovascular Events (MACE) free survival
Time frame: 3, 6, 12, 18, 24 (and 36) months
Classical 3-point MACE (cardiovascular death, nonfatal MI, or nonfatal stroke) and non-cardiovascular death. Measurements at 3, 6, 12, 18, 24 (and 36) months.
7 secondary outcomes
Functional outcome
Time frame: 3, 6, 12, 18, 24 months
Cognition
Time frame: 3, 6, 12, 18, 24 months
Number of falls
Time frame: 3, 6, 12, 18, 24 months
Time to first fall
Time frame: 3, 6, 12, 18, 24 months
General quality of life using the EQ-5D-5L
Time frame: 3, 6, 12, 18, 24 months
Societal costs
Time frame: 3, 6, 12, 18, 24 months
Cardiovascular risk status
Time frame: 3, 6, 12, 18, 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2025.
- Individual participant dataSharing planned: Yes. The SAFEST database can be requested by other researchers. These requests will be reviewed according the requirements for sharing SAFEST data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Renske van den Berg-Vos, Prof. dr. principal investigator
Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Nathalie van der Velde, Prof. dr. principal investigator
Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ischemic Stroke and TIA, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Susanna R Prins, MSc (0031 20 566 9111, s.r.prins@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health-Related Quality of Life (HrQoL) (time frame: 3, 6, 12, 18, 24 (and 36) months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2025.