StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Randomized Controlled Trial

NCT ID: NCT06785727

Last Updated: 2025-01-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 612 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2029-07-01

Brief Summary

Two Dutch guidelines (Stroke and Cardiovascular Risk Management) provide conflicting advice on optimal statin treatment in older patients. In the SAFEST - RCT, the investigators will assess the impact of starting versus not starting 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 Major Adverse Cardiovascular Events (MACE) free survival during a two-year follow-up period.

Detailed Description

Objective: To assess the impact of starting versus not starting 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.

Study population: The patient population consists of frail older (>=70 yrs) patients with a recent acute ischemic stroke or TIA who are admitted to the hospital or visit the outpatient clinic or emergency department for diagnostic evaluation, and who were not receiving statin treatment at the time of the acute event. Frailty is defined by a pre-event Clinical Frailty Scale (CFS) score of 4-7 and/or a post-event score of 6-7.

Description of intervention(s): Participants in the intervention group will start with a statin with target values following the Dutch stroke guideline. The control group will not start with a statin, aligning with the Dutch Cardiovascular Risk Management (CVRM) guideline recommendations.

Outcome measures:

This study has two co-primary endpoints: (1) Health-Related Quality of Life (HrQoL), using the Patient-Reported Outcomes Measurement Information System - Global-10 (PROMIS-10) and (2) Major Adverse Cardiovascular Events (MACE) free survival, after 2 years. We will evaluate these two co-primary outcomes at multiple time points, specifically at 3, 6, 12, 18, and 24 months. For patients enrolled in the beginning of recruitment, an extended follow-up of three years will be conducted to provide additional insights into the two primary endpoints.

Conditions

Ischemic Stroke; Transient Ischemic Attack

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Prescribing a statin

Newly prescribing a statin

Group Type: EXPERIMENTAL

Statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin or simvastatin)

Intervention Type: DRUG

The intervention group receives statin treatment following the current "Herseninfarct en Hersenbloeding" guideline. The intensity and target value of statin treatment are determined according to this national guideline. Which statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin) will be selected and what dose will be prescribed is left to the discretion of the treating neurologist. The statins are registered in the Netherlands and use will be according to the licenses of the products. They will be collected at the local pharmacy by the patient (following practice as usual).

Not prescribing a statin

Not prescribing a statin

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin or simvastatin)

The intervention group receives statin treatment following the current "Herseninfarct en Hersenbloeding" guideline. The intensity and target value of statin treatment are determined according to this national guideline. Which statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin) will be selected and what dose will be prescribed is left to the discretion of the treating neurologist. The statins are registered in the Netherlands and use will be according to the licenses of the products. They will be collected at the local pharmacy by the patient (following practice as usual).

Intervention Type: DRUG

Other Intervention Names

Lipitor, Lescol XL, Crestor, Zocor

Eligibility Criteria

Inclusion Criteria

• age = 70 years or older at the time of ischemic stroke or TIA;
• inclusion within 6 weeks after diagnosis of ischemic stroke or TIA;
• not 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 Scfale.[49]

Exclusion Criteria

• Patients with a stroke or TIA of non-atherosclerotic etiology.
• Previous serious adverse drug reactions (defined as an adverse reaction that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a birth defect40) 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 (a proxy is allowed to assist by writing on behalf of the participant in cases of physical incapacity or by discussing questions with the participant, but the proxy cannot make decisions for the participant).
• Inability or unwillingness to provide written informed consent, either independently or with the assistance of a proxy (a proxy is allowed to assist by writing on behalf of the participant in cases of physical incapacity or by discussing the consent form with the participant, but the proxy cannot make decisions or provide consent on behalf of the participant).
• Extremely high-risk patients, i.e. patients who have had two or more cardiovascular events within a period of one year.

• Minimum Eligible Age: 70 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VU University of Amsterdam

OTHER

Sponsor Role: collaborator

Prof. dr. Nathalie van der Velde

OTHER

Sponsor Role: lead

Responsible Party

Prof. dr. Nathalie van der Velde

Full Professor Geriatric medicine (internal medicine)

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Renske van den Berg, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Nathalie van der Velde, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Central Contacts

Birgit Damoiseaux-Volman, PhD

Role: CONTACT

b.a.damoiseaux@amsterdamumc.nl

0031 20 566 9111

Susanna Prins, MSc

Role: CONTACT

s.r.prins@amsterdamumc.nl

0031 20 566 9111

References

Prins SR, Damoiseaux-Volman BA, Vermeer SE, Bossuyt PMM, Van Eekelen R, Bosmans JE, Van Poelgeest EP, Martens FMAC, Emmelot-Vonk MH, Verstraete E, Muller M, Moll Van Charante EP, Lindhout M, Van Der Velde N, Van Den Berg-Vos RM. Rationale and design of 'StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack-the Randomized Controlled Trial' (SAFEST-RCT). BMJ Neurol Open. 2025 Oct 5;7(2):e001297. doi: 10.1136/bmjno-2025-001297. eCollection 2025.

Reference Type: DERIVED

PMID: 41070271 (View on PubMed)

Other Identifiers

2022-502059-79-00

Identifier Type: -

Identifier Source: org_study_id