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Trial record 1 of 1 for:    NCT01252875
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Treat Stroke to Target (TST)

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ClinicalTrials.gov Identifier: NCT01252875
Recruitment Status : Completed
First Posted : December 3, 2010
Last Update Posted : August 6, 2019
Sponsor:
Collaborators:
Pfizer
AstraZeneca
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE December 2, 2010
First Posted Date  ICMJE December 3, 2010
Last Update Posted Date August 6, 2019
Actual Study Start Date  ICMJE March 15, 2010
Actual Primary Completion Date May 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
recurrent ischemic stroke or stroke of undetermined origin, myocardial infarction, urgent coronary or carotid revascularization following new symptoms requiring hospitalization, and vascular death. [ Time Frame: each 6 months ]
recurrent ischemic stroke or stroke of undetermined origin, myocardial infarction, urgent coronary or carotid revascularization following new symptoms requiring hospitalization, and vascular death.
Original Primary Outcome Measures  ICMJE
 (submitted: December 2, 2010)
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 ]
Recurrent of non fatal stroke, non fatal IM, and vascular death
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Recurrent nonfatal ischemic stroke [ Time Frame: each 6 months ]
    Recurrent nonfatal ischemic stroke
  • Nonfatal myocardial infarction [ Time Frame: each 6 months ]
    Nonfatal myocardial infarction
  • Recurrent ischemic stroke, fatal or non [ Time Frame: each 6 months ]
    Recurrent ischemic stroke, fatal or non
  • Recurrent ischemic stroke or TIA [ Time Frame: each 6 months ]
    Recurrent ischemic stroke or TIA
  • Intracranial hemorrhage (intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma) [ Time Frame: each three weeks until target is not achieved then each 6 months ]
    Intracranial hemorrhage (intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma)
  • All stroke (ischemic or hemorrhagic) [ Time Frame: each three weeks until target is not achieved then each 6 months ]
    All stroke (ischemic or hemorrhagic)
  • Any major coronary events (including fatal and nonfatal myocardial infarction) [ Time Frame: each 6 months ]
    Any major coronary events (including fatal and nonfatal myocardial infarction)
  • Any coronary heart disease end-point (myocardial infarction, hospitalization for acute corornary symptoms, coronary revascularization procedure) [ Time Frame: each 6 months ]
    Any coronary heart disease end-point (myocardial infarction, hospitalization for acute corornary symptoms, coronary revascularization procedure)
  • Any revascularisation procedure (coronary, carotid, or peripheral artery)) [ Time Frame: each 6 months ]
    Any revascularisation procedure (coronary, carotid, or peripheral artery))
  • Carotid artery revascularization procedure (urgent following new symptoms or elective) [ Time Frame: each 6 months ]
    Carotid artery revascularization procedure (urgent following new symptoms or elective)
  • Vascular death (ischemic stroke or undetermined stroke, fatal myocardial infarction, other vascular deaths, sudden death, death of undetermined cause, i.e., without other cause documented such as cancer, infection, accident, suicide, etc…) [ Time Frame: each 6 months ]
    Vascular death (ischemic stroke or undetermined stroke, fatal myocardial infarction, other vascular deaths, sudden death, death of undetermined cause, i.e., without other cause documented such as cancer, infection, accident, suicide, etc…)
  • All causes deaths [ Time Frame: each 6 months ]
    All causes deaths
  • Primary endpoint plus intracranial hemorrhage [ Time Frame: each 6 months ]
    Primary endpoint plus intracranial hemorrhage
  • New onset diabetes [ Time Frame: each 6 months ]
    New onset diabetes
Original Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2010)
Recurrent of fatal and non fatal stroke, stroke and TIA. [ Time Frame: each three weeks until target is not achieved then each 6 months ]
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treat Stroke to Target
Official Title  ICMJE 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.
Brief Summary

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.

Detailed Description

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:

Recurrent ischemic stroke or stroke of undetermined origin, myocardial infarction, urgent coronary or carotid revascularization following new symptoms requiring hospitalization, and vascular death.

Secondary endpoints:

  • Recurrent nonfatal ischemic stroke
  • Nonfatal myocardial infarction
  • Recurrent ischemic stroke, fatal or non
  • Recurrent ischemic stroke or TIA
  • Intracranial hemorrhage (intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma)
  • All stroke (ischemic or hemorrhagic)
  • Any major coronary events (including fatal and nonfatal myocardial infarction)
  • Any coronary heart disease end-point (myocardial infarction, hospitalization for acute corornary symptoms, coronary revascularization procedure)
  • Any revascularisation procedure (coronary, carotid, or peripheral artery))
  • Carotid artery revascularization procedure (urgent following new symptoms or elective)
  • Vascular death (ischemic stroke or undetermined stroke, fatal myocardial infarction, other vascular deaths, sudden death, death of undetermined cause, i.e., without other cause documented such as cancer, infection, accident, suicide, etc…)
  • All causes deaths
  • Primary endpoint plus intracranial hemorrhage
  • New onset diabetes

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Ischemic Stroke
  • Transient Ischemic Attack
  • Atherosclerotic Stenosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 15, 2019)
2873
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2010)
3760
Actual Study Completion Date  ICMJE May 26, 2019
Actual Primary Completion Date May 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01252875
Other Study ID Numbers  ICMJE P081244
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE
  • Pfizer
  • AstraZeneca
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Pierre Amarenco, MD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date June 2019

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