Treat Stroke to Target (TST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborators:
Pfizer
AstraZeneca
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01252875
First received: December 2, 2010
Last updated: December 9, 2013
Last verified: December 2013

December 2, 2010
December 9, 2013
March 2010
September 2018   (final data collection date for primary outcome measure)
Recurrent of non fatal stroke, non fatal IM, and vascular death [ Time Frame: each three weeks until target is not achieved then each 6 months ] [ Designated as safety issue: No ]
Recurrent of non fatal stroke, non fatal IM, and vascular death
Same as current
Complete list of historical versions of study NCT01252875 on ClinicalTrials.gov Archive Site
Recurrent of fatal and non fatal stroke, stroke and TIA. [ Time Frame: each three weeks until target is not achieved then each 6 months ] [ Designated as safety issue: No ]
Recurrent of fatal and non fatal stroke, stroke and TIA, major coronary event (MI, sudden death, coronary revascularization for an ACS), any coronary endpoints (MI, hospitalization for ACS, coronary revascularization), any revascularization procedures (coronary, carotid, peripheral), carotid revascularization (either surgical or endovascular), vascular death, total death
Same as current
Not Provided
Not Provided
 
Treat Stroke to Target
EVALUATION OF TWO SECONDARY CARE STRATEGIES AFTER STROKE OR TRANSIENT ISCHEMIC ATTACK (TIA): ACHEIVED TARGET LDL-C TO 100 mg/dL (+/- 10,mg/dL) OR LESS THAN 70 mg/dL.

The aim of this study is the evaluation of two usual care strategies after stroke or TIA : achieved target LDL-C of 100 mg/dL (+/-10 mg/dL) or less than 70 mg/dL. Investigators will use the statin and titrate the dosage to achieve the target assigned by randomization in monotherapy or in combination with ezetimibe or other drugs.

The primary end-point is the occurrence of recurrent non fatal stroke, non fatal MI, and vascular death in each group.

3760 patients will be recruited and followed for eight and a half years maximum.

The aim of this study is the evaluation of two usual care strategies after stroke or TIA : achieved target LDL-C of 100 mg/dL (+/-10 mg/dL) or less than 70 mg/dL. Investigators will use the statin and titrate the dosage to achieve the target assigned by randomization in monotherapy or in combination with ezetimibe or other drugs.

Inclusion criteria:

  • Recent (less than 3 months) ischemic stroke As soon as possible after the event, once the neurologic deficit is stabilized (investigator judgment). These ischemic strokes include TIA with ischemic lesion documented by CT or MRI.
  • Or recent TIA (less than 15 days) without documentation of ischemic lesion on CT/MR imaging. Must be limb weakness or aphasia lasting more than 10 min.
  • And documented atherosclerotic stenosis in carotid artery (investigator judgment) (based on the results of Duplex echography, CTA, MRA or X ray- angiography), Or in the aortic arch (investigator judgment) (based on TEE or CTA), Or in other brain artery: vertebral, basilar or other intracranial artery (based on CTA, MRA, XRA), Or in coronary arteries (past history of acute coronary syndrome, coronary revascularization or positive coronary angiography)
  • And statin treatment is indicated, following ANSM guidelines (French drug agency), age >18 years, rankin score ≤ 4, patient or a legal representative signs consent, patient is affiliated to social security system

Exclusion criteria :

  • Ischemic stroke/TIA du to arterial dissection (investigator judgment)
  • Cardiac source of embolism (e.g., mitral stenosis, endomyocardial fibrosis) without documented atherosclerotic stenosis : a patient with atrial fibrillation or a past history of recent myocardial infarction or calcified aortic stenosis can be randomized if he otherwise fulfils inclusion criteria
  • Symptomatic hemorrhagic stroke : Presence of microbleeds on gradient echo imaging (T2*) is not an exclusion criteria. Hemorrhagic transformation of an ischemic stroke is not an exclusion criteria
  • Uncontrolled hypertension (investigator judgment)
  • LDL-C <100 mg/dL or patients for whom treatment intensification is impossible
  • F/U impossible or bad observance anticipated.
  • Co-morbid condition that may interfere with the F/U or with the evaluation of primary endpoint
  • Participation to another clinical trial

The primary end-point is:

occurrence of recurrent non fatal stroke, non fatal MI, and vascular death in each group.

Secondary endpoints:

  • Fatal and non fatal stroke
  • Stroke and TIA
  • Major coronary event (MI, sudden death, coronary revascularization for an ACS)
  • Any coronary endpoints (MI, hospitalization for ACS, coronary revascularization)
  • Any revascularization procedures (coronary, carotid, peripheral)
  • Carotid revascularization (either surgical or endovascular)
  • Vascular death
  • Total death

Hypothesis :

  • Follow-up of three years
  • Risk of primary end-point in the control group (Target LDL <100 mg/dL) : 4% per year (12 % at 36 months)
  • 5% Alpha, 80% power, total number of subject is :
  • 3068 patients with a RRR 25%
  • 20% drop-out: 3760 patients (385 primary EP)

Study specifications Follow-up : eight and a half years Follow-up visit : every 6 months Number of centers (French Stroke Units, under the auspice of the French Neurovascular Society) : 60-100

Ancillary study As an ancillary study, 800 patients (400 in each arm in 4 centers) will participate in the TST-PLUS (Plaque Ultrasound Study), in which they will have three ultrasound examination (baseline, 1 year and 3 years) and baseline blood sampling. The primary endpoint of this substudy will be the rate of occurrence of new carotid plaque, with the hypothesis that Rate of plaque occurrence in the <100 mg/dL group will be 25% after 3 years (45% in EVA when atherosclerosis was present at baseline) RRR of plaque of 25% in the <70 mg/dL group Alpha 5%, power 80%

As an ancillary study, 1000 patients will participate in the TST-PGS (Pharmacogenetics) Study, in which they will have 1 blood sampling either at baseline or during one of the follow-up visits of TST. The aim of this study is to show that the benefit (risk of ischemic stroke, myocardial infarction, and vascular death) observed with a strategy of LDL-C <0.7 g / l compared to a strategy of LDL-C to 1 ± 0.1 g / l is higher in carriers of polymorphism 719Arg of the gene KIF-6 than non-carriers of this polymorphism.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Ischemic Stroke
  • Transient Ischemic Attack
  • Atherosclerotic Stenosis
  • Procedure: Target : 100 mg/dL (+/-10 mg/dL)
    Statin +/- other lipid lowering therapy during 3 years, Target : LDL-C =100 mg/dL (+/-10 mg/dL), recording recurrent non fatal stroke, non fatal MI, and vascular death and others endpoints such as new onset diabetes, hemorrhagic strokes.
    Other Name: treat to target
  • Procedure: 70 mg/dL
    Statin +/-lipid lowering therapy during eight and a half years maximum, Target : LDL-C concentration of less than 70 mg/dL, recording recurrent of non fatal stroke, non fatal IM, and vascular death and others endpoints such as: new onset diabetes, hemorrhagic strokes.
    Other Name: treat to target
  • LDL-C to100 mg/dL (+/-10 mg/dL)

    Target : 100 mg/dL (+/-10 mg/dL):

    Patients recruited in this arm will receive statin +/-other lipid lowering therapy in order to reach a LDL-C concentration of 100 mg/dL(+/-10 mg/dL).

    Intervention: Procedure: Target : 100 mg/dL (+/-10 mg/dL)
  • LDL-C < 70 mg/dL
    70 mg/dL: Patients recruited in this arm will receive statin +/-other lipid lowering therapy in order to reach a LDL-C concentration of less than 70 mg/dL.
    Intervention: Procedure: 70 mg/dL
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
3760
September 2018
September 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • • Recent (less than 3 months) ischemic stroke
  • As soon as possible after the event, once the neurologic deficit is stabilized (investigator judgment)
  • These ischemic strokes include TIA with ischemic lesion documented by CT or MRI

    • Or recent TIA (less than 15 days)

  • without documentation of ischemic lesion on CT/MR imaging
  • Must be limb weakness or aphasia lasting more than 10 min

    • And documented atherosclerotic stenosis

  • In carotid artery (investigator judgment) (based on the results of Duplex echography, CTA, MRA or X ray- angiography)
  • Or in the aortic arch (investigator judgment) (based on TEE or CTA)
  • Or in other brain artery: vertebral, basilar or other intracranial artery (based on CTA, MRA, XRA)
  • Or in coronary arteries (past history of acute coronary syndrome, coronary revascularization or positive coronary angiography)

    • And

  • Statin treatment is indicated, following ANSM guidelines (French drug agency)
  • age >18 years
  • rankin score ≤ 4
  • patient or a legal representative signs consent
  • Patient is affiliated to social security system

Exclusion Criteria:

  • • Ischemic stroke/TIA du to
  • arterial dissection (investigator judgment)
  • Cardiac source of embolism (e.g., mitral stenosis, endomyocardial fibrosis) without documented atherosclerotic stenosis : a patient with atrial fibrillation or a past history of recent myocardial infarction or calcified aortic stenosis can be randomized if he otherwise fulfils inclusion criteria

    • Symptomatic hemorrhagic stroke

  • Presence of microbleeds on gradient echo imaging (T2*) is not an exclusion criteria.
  • Hemorrhagic transformation of an ischemic stroke is not an exclusion criteria

    • Uncontrolled hypertension (investigator judgment)
    • LDL-C <100 mg/dL or patients for whom treatment intensification is impossible
    • F/U impossible or bad observance anticipated.
    • Co-morbid condition that may interfere with the F/U or with the evaluation of primary endpoint
    • Participation to another clinical trial
Both
18 Years and older
No
Contact: Pierre Amarenco, MD +33 (0) 1 40 25 87 26 pierre.amarenco@bch.aphp.fr
France
 
NCT01252875
P081244
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
  • Pfizer
  • AstraZeneca
  • Merck Sharp & Dohme Corp.
Principal Investigator: Pierre Amarenco, MD Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP