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

September 15, 2023 updated by: Stefan Engelter

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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

194

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Copenhagen, Denmark
        • University Hospital, Stroke Center Bispebjerg Hospital Copenhagen, Denmark
      • Berlin, Germany
        • University Hospital, Stroke Center Charite Berlin, Germany
      • Munich, Germany
        • University Hospital, Stroke Center LMU Munich, Germany
      • Aarau, Switzerland
        • Kantonsspital, Stroke Center Aarau, Switzerland
      • Basel, Switzerland
        • University Hospital, Stroke Center Basel, Switzerland
      • Berne, Switzerland
        • University Hospital, Stroke Center Inselspital Berne, Switzerland
      • Geneva, Switzerland
        • University Hospital, Stroke Center Geneva, Switzerland
      • Lausanne, Switzerland
        • University Hospital, Stroke Center CHUV Lausanne, Switzerland
      • St. Gallen, Switzerland
        • Kantonsspital, Stroke Center St. Gallen, Switzerland
      • Zurich, Switzerland
        • University Hospital, Stroke Center Zurich, Switzerland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 least one):

    • 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.
  3. Written informed consent by patient or next-to-kin
  4. 24h latency period in case of thrombolysis
  5. Age > 18 years by time of inclusion

Exclusion Criteria:

  1. MR-contraindications (claustrophobia precluding MRI: patients agreeing to undergo MRI scanning with mild sedation may be entered into the study)
  2. Contraindications to the use of anticoagulation (vitamin k antagonists, heparin) or ASA (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/) and the judgment of the treating physician)
  3. Pregnancy (Note: for women in child bearing age a pregnancy test has to be done prior to study entry)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Oral Anticoagulation
Vitamin K-Antagonists, target INR 2.0-3.0
Vitamin K-antagonists, target INR 2.0-3.0
Other Names:
  • Phenprocoumon, Warfarin, Acenocoumarol
Experimental: Antiplatelets
Acetylsalicylic acid, 300mg o.p.d.
Acetylsalicylic acid, 300mg o.p.d.
Other Names:
  • ASA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary composite outcome measure - labeled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) -
Time Frame: 3 months
CIHD - includes the following efficacy and safety outcome measures during the treatment period: includes the following efficacy and safety outcome measures during the treatment period: (i) occurrence of any stroke (including retinal infarction), new acute lesions on diffusion weighted MRI (ii) any major extracranial hemorrhage, any symptomatic intracranial hemorrhage and any asymptomatic micro- or macrobleeds, (iii) death.
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
new ischemic strokes (including retinal infarction)
Time Frame: 3 months
3 months
new acute lesions on diffusion-weighted MRI
Time Frame: 3 months
3 months
any major extracranial hemorrhage
Time Frame: 3 months
3 months
any symptomatic intracranial hemorrhage
Time Frame: 3 months
3 months
any asymptomatic micro- or macrobleeds
Time Frame: 3 months
3 months
any death
Time Frame: 3 months
3 months
any increase in volume of the vessel wall hematoma at the followup cervical MRI as compared to the baseline MR-scan
Time Frame: 3 months
3 months
independence in activity of daily living (modified Rankin scale 0-2) at 3 months and at 6 months
Time Frame: 3 months
3 months
excellent functional outcome (modified Rankin scale 0,1) at 3 month and at 6 months
Time Frame: 3 months
3 months
any TIA (classical definition)
Time Frame: 3 months
3 months
recurrent cervical artery dissection
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Stefan T. Engelter, MD, University Hospital, Neurorehab. Felix Platter, University of Basel, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

June 1, 2019

Study Completion (Actual)

June 1, 2019

Study Registration Dates

First Submitted

January 23, 2014

First Submitted That Met QC Criteria

January 23, 2014

First Posted (Estimated)

January 27, 2014

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 15, 2023

Last Verified

September 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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