Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection - TREAT-CAD

Last updated: May 18, 2024
Sponsor: Stefan Engelter
Overall Status: Completed

Phase

3

Condition

Chest Pain

Cardiovascular Disease

Occlusions

Treatment

Acetylsalicylic acid

Vitamin K antagonist

Clinical Study ID

NCT02046460
340/12
  • Ages > 18
  • All Genders

Study Summary

Primary objective: To demonstrate the non-inferiority of acetylsalicylic acid (ASA) to anticoagulant treatment (vitamin K antagonists) in CAD-patients with regard to outcome and complication measures.

Methods: Randomized controlled, open labeled multicenter, non-inferiority trial with blinded assessment of outcome events.

Primary endpoint: Primary composite outcome measure - labeled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) - includes the following efficacy and safety outcome measures during the treatment period: (i) occurrence of any stroke*, new acute lesions on diffusion weighted MRI (ii) any major extracranial hemorrhage, any symptomatic intracranial hemorrhage and any asymptomatic micro- or macrobleeds, (iii) death.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Acute ischemic or non-ischemic symptoms within 2 weeks

  2. Verification of CAD-diagnosis (carotid and/or vertebral) by MR-techniques (at leastone):

  • mural hematoma or

  • pseudo-aneurysm or

  • long filiform stenosis or

  • intimal flap or

  • double lumen or

  • occlusion situated more than 2 cm above the bifurcation of the carotid artery,revealing a pseudo aneurysm or a long filiform stenosis after recanalisation.

  1. Written informed consent by patient or next-to-kin

  2. 24h latency period in case of thrombolysis

  3. Age > 18 years by time of inclusion

Exclusion

Exclusion Criteria:

  1. MR-contraindications (claustrophobia precluding MRI: patients agreeing to undergoMRI scanning with mild sedation may be entered into the study)

  2. Contraindications to the use of anticoagulation (vitamin k antagonists, heparin) orASA (according to the Swiss "Arzneimittelkompendium"http://www.compendium.ch/search/de or the "Rote Liste" (German centers) or "Lægemiddelstyrelsen - produktresume" for the Danish center (https://laegemiddelstyrelsen.dk/da/bivirkninger/find-medicin/produktresumeer/) andthe judgment of the treating physician)

  3. Pregnancy (Note: for women in child bearing age a pregnancy test has to be doneprior to study entry)

Study Design

Total Participants: 194
Treatment Group(s): 2
Primary Treatment: Acetylsalicylic acid
Phase: 3
Study Start date:
September 01, 2013
Estimated Completion Date:
June 30, 2019

Study Description

Substudies:

  1. In-depth analysis of the TREAT-CAD randomized trial:

    The investigators will perform a subgroup analysis on the per-protocol population investigating if the antithrombotic treatment effect (anticoagulation versus aspirin) depends on specific patient baseline characteristics. The investigators will look at the following subgroups: Presenting with cerebral ischemia - either clinical ischemic events, MRI lesions, or both - versus presenting with local symptoms only, occlusion of the dissected artery at baseline (no/yes), early versus delayed treatment start (divided by the median of the study population), acute recanalization therapy including intravenous thrombolysis and/or endovascular therapy (no/yes), intracranial extension of the dissected artery (no/yes), site of dissection defined as internal carotid artery dissection versus vertebral artery dissection, single versus multivessel dissection, younger versus older age (divided by the median of the study population), and male versus female.

  2. TCD Monitoring Substudy:

    The objective of the TREAT-CAD transcranial Doppler (TCD) substudy is to (i) detect the frequency of microembolic signals (MES) in CAD patients, stratified to the type of treatment (aspirin vs. anticoagulation) - in the setting of an RCT (randomized controlled trial)- and (ii) to evaluate the meaning of MES by addressing the following questions: (a) Is there an association of MES (presence or number) with the occurrence of clinical and/or surrogate MR (magnetic resonance) outcome measures; (b) Is there an interaction between MES, type of treatment and outcome events. Participants are asked to allow a 6-h TCD monitoring in between day 1 and day 4 since start of the allocated study treatment. Recordings were allowed to be split in up to three episodes (2 h each). In patients with ICAD (internal carotid artery dissection), the ipsilateral middle cerebral artery is investigated. In patients with VAD (vertebral artery dissection), the ipsilateral posterior cerebral artery is investigated.

  3. Biomarker substudy:

    The objective of the biomarker study is to investigate whether the plasma level of MMP9 (matrix-metalloproteinase 9) and the ratio of the plasma MMP9 to TIMP2 (tissue inhibitor of metalloproteinases 2) is associated with efficacy and safety measures in CAD patients, when stratified to the allocated treatment regime. Plasma samples are collected from participants at baseline (i.e., prior to start of the allocated treatment within the TREAT-CAD main study) and at Follow-up visit 1. The specific focus on MMP9 and TIMP2 is based on preliminary observational data pointing to higher MMP9 and MMP9/TIMP2 ratios in CAD versus control patients.

  4. 6 Month-follow-up for TREAT-CAD To compare (i) the frequency of clinical and MRI outcomes 6 months after cervical artery dissection among the per-protocol participants of the TREAT-CAD trial and (ii) to focus on events occurring between 3 and 6 months, stratified to the type of antithrombotic medication taken (as-treated analysis).

  5. Detailed imaging analysis in the TREAT-CAD study To identify possible imaging risk factors for recurrent stroke and to evaluate the dependence of antithromobotic therapy on imaging factors.

Connect with a study center

  • University Hospital, Stroke Center Bispebjerg Hospital Copenhagen, Denmark

    Copenhagen,
    Denmark

    Site Not Available

  • University Hospital, Stroke Center Charite Berlin, Germany

    Berlin,
    Germany

    Site Not Available

  • University Hospital, Stroke Center LMU Munich, Germany

    Munich,
    Germany

    Site Not Available

  • University Hospital Basle, Stroke Center Basle

    Basle, BS 4031
    Switzerland

    Site Not Available

  • Kantonsspital, Stroke Center Aarau, Switzerland

    Aarau,
    Switzerland

    Site Not Available

  • University Hospital, Stroke Center Basel, Switzerland

    Basel,
    Switzerland

    Site Not Available

  • University Hospital, Stroke Center Inselspital Berne, Switzerland

    Berne,
    Switzerland

    Site Not Available

  • University Hospital, Stroke Center Geneva, Switzerland

    Geneva,
    Switzerland

    Site Not Available

  • University Hospital, Stroke Center CHUV Lausanne, Switzerland

    Lausanne,
    Switzerland

    Site Not Available

  • Kantonsspital, Stroke Center St. Gallen, Switzerland

    St. Gallen,
    Switzerland

    Site Not Available

  • University Hospital, Stroke Center Zurich, Switzerland

    Zurich,
    Switzerland

    Site Not Available

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