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

NCT06785727 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2022-502059-79-00
• Study Type: interventional
• Target: 612
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ischemic Stroke; Transient Ischemic Attack

Keywords

statin; ischemic stroke; transient ischemic attack; quality of life

Outcome Measures

Primary Outcomes (2)

• 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.

  3, 6, 12, 18, 24 (and 36) months.

• Major Adverse Cardiovascular Events (MACE) free survival

  Classical 3-point MACE (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and non-cardiovascular death. Measurements at3, 6, 12, 18, 24 (and 36) months.

  3, 6, 12, 18, 24 (and 36) months.

Secondary Outcomes (7)

• Functional Outcome

  1 and 2 years

• Cognition MoCA

  1 and 2 years

• Number of falls

  1 and 2 years

• Time to first fall

  2 years

• General quality of life EuroQol Questionnaire (EQ-5D-5L)

  1 and 2 years

Study Arms (2)

Prescribing a statin

EXPERIMENTAL

Newly prescribing a statin

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

Not prescribing a statin

NO INTERVENTION

Not prescribing a statin

Interventions

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

Also known as: Lipitor, Lescol XL, Crestor, Zocor

Prescribing a statin

Eligibility Criteria

• Age: 70 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• age = 70 years or older at the time 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.\[49\]

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prof. dr. Nathalie van der Velde: lead
• VU University of Amsterdam: collaborator

Related Publications (1)

• 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.

  PMID: 41070271 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Ischemic Attack, Transient

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Fluvastatin; Pravastatin; Rosuvastatin Calcium; Simvastatin

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines; Lovastatin

Study Officials

• Renske van den Berg, Prof. dr.

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

  PRINCIPAL INVESTIGATOR

• Nathalie van der Velde, Prof. dr.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Birgit Damoiseaux-Volman, PhD

CONTACT

0031 20 566 9111; b.a.damoiseaux@amsterdamumc.nl

Susanna Prins, MSc

CONTACT

0031 20 566 9111; s.r.prins@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor Geriatric medicine (internal medicine)

Model Details: Multicentre prospective randomized open-label approach with blinded end-points evaluation (PROBE)

Study Record Dates

• First Submitted: January 16, 2023
• First Posted: January 21, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 21, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After data-collection/analysis.
• Access Criteria: Requirements for sharing SAFEST data include: * privacy laws of the Netherlands, policy of NFU and AmsterdamUMC must be followed * data will anonymously * data can only be used to study the research question for which participants signed the ICF * data will not be shared for commercial purposes.