StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack – The Randomized Controlled Trial

2024-517343-31-00 Protocol NL86273.100.24 Therapeutic use (Phase IV) Ongoing, recruiting

Start 11 Apr 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 23 sites · Protocol NL86273.100.24

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 600
Countries 1
Sites 23

Ischemic stroke and transient ischemic attack

To evaluate the effect of initiating statin therapy versus no statin therapy on Major Adverse Cardiovascular Events (MACE)-free survival and health-related quality of life (HRQoL) over a two-year follow-up in frail individuals aged 70 and above with a recent ischemic stroke or TIA.

Key facts

Sponsor
Amsterdam UMC Stichting
Participant type
Patients
Age range
65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
11 Apr 2025 → ongoing
Decision date (initial)
2024-12-10
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No
Funding sources
ZonMw

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the effect of initiating statin therapy versus no statin therapy on Major Adverse Cardiovascular Events (MACE)-free survival and health-related quality of life (HRQoL) over a two-year follow-up in frail individuals aged 70 and above with a recent ischemic stroke or TIA.

Secondary objectives 1

  1. To assess the impact of statin therapy on cognitive functioning, frailty progression, functional outcomes, and societal costs.

Conditions and MedDRA coding

Ischemic stroke and transient ischemic attack

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2022-502059-79-00 StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack Amsterdam UMC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. A recent ischemic stroke or TIA (within 6 weeks before inclusion)
  2. Age equal to or greater than 70 years at the time of the ischemic stroke or TIA
  3. Frailty, as defined by a pre-event score of 4-7 and/or a post-event score of 6-7 on the validated Clinical Frailty Scale
  4. Not using statin therapy at the time of the index event

Exclusion criteria 5

  1. Previous serious adverse drug reactions (defined as an adverse reaction that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitaliza-tion, results in persistent or significant disability or incapacity, or is a birth defect) to statins or other contraindications to statin use.
  2. Very severe frailty or very limited life expectancy (< 6 months) as defined by a score >= 8 points on the validated Clinical Frailty Scale
  3. Inability to communicate in Dutch
  4. Inability to respond to questions, either independently or with the assistance of a proxy.
  5. Inability or unwillingness to provide written informed consent, either independently or with the assistance of a proxy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. • MACE-free survival over a two-year period, measured at 3, 6, 12, 18, and 24 months, with additional follow-up at three years for those enrolled early in the recruitment phase.
  2. • Health-Related Quality of Life (HRQoL) measured using the Patient-Reported Outcomes Measurement Information System - Global-10 (PROMIS-10) at 3, 6, 12, 18, and 24 months, with additional follow-up at three years for those enrolled early in the recruitment phase.

Secondary endpoints 5

  1. Number of new major cardiovascular events
  2. Cognitive function at 12 and 24 months.
  3. Falls (number and time to first fall)
  4. Frailty status at 12 and 24 months.
  5. Functional outcome at 12 and 24 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Fluvastatine 20 mg PCH, capsules

PRD626456 · Product

Active substance
Fluvastatin
Pharmaceutical form
CAPSULE
Route of administration
ORAL
Max daily dose
80 mg milligram(s)
Max total dose
87600 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
C10AA04 — FLUVASTATIN
Marketing authorisation
RVG 34892
MA holder
PHARMACHEMIE BV
MA country
Netherlands
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Atorvastatine Viatris 10 mg Filmtabletten

PRD10573698 · Product

Active substance
Atorvastatin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
80 mg milligram(s)
Max total dose
87600 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
C10AA05 — ATORVASTATIN
Marketing authorisation
BE383695
MA holder
VIATRIS GX
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Pravastatine Viatris 10 mg Tabletten

PRD10513172 · Product

Active substance
Pravastatin Sodium
Substance synonyms
SODIUM (3R,5R)-7-{(1S,2S,6S,8S,8AR)-1,2,6,7,8,8A-HEXAHYDRO-6-HYDROXY-2-METHYL-8-[(S)-2-METHYLBUTYRYLOXY]-1-NAPHTHYL}-3,5-DIHYDROXYHEPTANOATE
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
80 mg milligram(s)
Max total dose
87600 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
C10AA03 — PRAVASTATIN
Marketing authorisation
BE373213
MA holder
VIATRIS GX
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Simvastatine Mylan 40 mg, filmomhulde tabletten

PRD10016855 · Product

Active substance
Simvastatin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
80 mg milligram(s)
Max total dose
87600 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
C10AA01 — SIMVASTATIN
Marketing authorisation
RVG 30106
MA holder
MYLAN PHARMACEUTICALS LIMITED
MA country
Netherlands
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Rosuvastatine Viatris 5 mg Filmtabletten

PRD10919029 · Product

Active substance
Rosuvastatin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
80 mg milligram(s)
Max total dose
87600 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
C10AA07 — ROSUVASTATIN
Marketing authorisation
BE440815
MA holder
VIATRIS GX
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

75 Total trials 44 Recruiting 14 Ended
Academic / Non-commercial
Sponsor organisation
Amsterdam UMC Stichting
Address
Meibergdreef 9
City
Amsterdam
Postcode
1105 AZ
Country
Netherlands

Scientific contact point

Organisation
Amsterdam UMC Stichting
Contact name
Prof. dr. R.M. van den Berg - Vos

Public contact point

Organisation
Amsterdam UMC Stichting
Contact name
Prof. dr. R.M. van den Berg - Vos

Locations

1 EU/EEA country · 23 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 600 23
Rest of world — 0 —

Investigational sites

Netherlands

23 sites · Ongoing, recruiting
Erasmus Medisch Centrum 1
Neurologie, Dr Molewaterplein 40, 3015 GD, Rotterdam
Elkerliek Ziekenhuis
Neurologie, Wesselmanlaan 25, 5707 HA, Helmond
Leids Universitair Medisch Centrum (LUMC)
Neurologie, Albinusdreef 2, 2333 ZA, Leiden
UMC Groningen
Neurologie, Hanzeplein 1, 9700RB, Groningen
Isala Klinieken Stichting
Neurologie, Dokter Van Heesweg 2, 8025 AB, Zwolle
Stichting Viecuri Medisch Centrum voor Noord-Limburg
Neurologie, Tegelseweg 210, 5912 BL, Venlo
Gelre Hospitals
Neurology, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn
Stichting OLVG
Neurologie, Jan Tooropstraat 164, 1061 AE, Amsterdam
Maasstad Ziekenhuis Stichting
Neurologie, Maasstadweg 21, 3079 DZ, Rotterdam
Zuyderland Medisch Centrum Stichting
Neurologie, Henri Dunantstraat 5, 6419 PC, Heerlen
Rijnstate Ziekenhuis Stichting
Neurologie, Wagnerlaan 55, 6815 AD, Arnhem
Jeroen Bosch Ziekenhuis Stichting
Neurologie, Henri Dunantstraat 1, 5223 GZ, 'S-Hertogenbosch
Academisch Ziekenhuis Maastricht
Neurologie, P Debyelaan 25, 6229 HX, Maastricht
Amsterdam UMC Stichting
Neurology, Meibergdreef 9, 1105 AZ, Amsterdam
Catharina Ziekenhuis Stichting
Neurology, Michelangelolaan 2, 5623 EJ, Eindhoven
Sint Franciscus Vlietland Groep Stichting
Neurologie, Kleiweg 500, 3045 PM, Rotterdam
Flevoziekenhuis Stichting
Neurologie, Hospitaalweg 1, 1315 RA, Almere
Medisch Spectrum Twente
Neurologie, Koningsplein 1, 7512 KZ, Enschede
Haaglanden Medisch Centrum Stichting
Neurology, Lijnbaan 32, 2512 VA, 'S-Gravenhage
Stichting Elisabeth-Tweesteden Ziekenhuis
Neurology, Hilvarenbeekseweg 60, 5022 GC, Tilburg
Universitair Medisch Centrum Utrecht
Neurology, Heidelberglaan 100, 3584 CX, Utrecht
Frisius MC
Neurology, Henri Dunantweg 2, 8934 AD, Leeuwarden
St. Antonius Ziekenhuis
Neurology, Koekoekslaan 1, 3435 CM, Nieuwegein

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2025-04-11 2025-04-11

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1 Protocol 2024-517343-31-00 1
Protocol (for publication) D4 Gebeurteniskalender SAFEST-RCT 1
Protocol (for publication) D4 Vragenlijsten SAFEST-RCT 1
Recruitment arrangements (for publication) K1 Recruitment procedure SAFEST-RCT 1
Subject information and informed consent form (for publication) E3 Flyer SAFEST RCT versie 2 dd 29-04-2025 with TT 2
Subject information and informed consent form (for publication) L1 SIS and ICF 2024-517343-31-00 1
Subject information and informed consent form (for publication) L2 Flyer SAFEST-RCT 2
Summary of Product Characteristics (SmPC) (for publication) E2 SmPC Atorvastatine 1
Summary of Product Characteristics (SmPC) (for publication) E2 SmPC Fluvastatine 1
Summary of Product Characteristics (SmPC) (for publication) E2 SmPC Pravastatine 1
Summary of Product Characteristics (SmPC) (for publication) E2 SmPC Rosuvastatine 1
Summary of Product Characteristics (SmPC) (for publication) E2 SmPC Simvastatine 1
Synopsis of the protocol (for publication) D1 Dutch synopsis of the protocol 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-19 Netherlands Acceptable
2024-12-06
 2024-12-10
2 SUBSTANTIAL MODIFICATION SM-2 2025-05-26 Netherlands Acceptable 2025-06-18
3 SUBSTANTIAL MODIFICATION SM-3 2025-12-01 Netherlands Acceptable 2025-12-17

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