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Cervical Artery DissectionPhase 3TREAT-CADNCT02046460

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

A Phase 3 study testing Acetylsalicylic acid and Vitamin K antagonist in people with Cervical Artery Dissection, run by Stefan Engelter at 10 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cervical Artery Dissection
What is being tested?
Acetylsalicylic acid and Vitamin K antagonist
Could I receive a placebo?
No, everyone receives an active treatment
How many people
194 participants
Where
10 sitesin 3 countries
Study dates
Sep 2013to Jun 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute ischemic or non-ischemic symptoms within 2 weeks
  • 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
Show all 11Show fewer
  • 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.
  • Written informed consent by patient or next-to-kin
  • 24h latency period in case of thrombolysis
  • Age > 18 years by time of inclusion

Who cannot join

  • MR-contraindications (claustrophobia precluding MRI: patients agreeing to undergo MRI scanning with mild sedation may be entered into the study)
  • 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)
  • Pregnancy (Note: for women in child bearing age a pregnancy test has to be done prior to study entry)

Trial locations and contacts

10 sites in 3 countries.

10 sites in 3 countries

Switzerland7 sites
  • Kantonsspital, Stroke Center Aarau, Switzerland

    Aarau

  • University Hospital, Stroke Center Basel, Switzerland

    Basel

  • University Hospital, Stroke Center Inselspital Berne, Switzerland

    Bern

  • University Hospital, Stroke Center Geneva, Switzerland

    Geneva

  • University Hospital, Stroke Center CHUV Lausanne, Switzerland

    Lausanne

  • Kantonsspital, Stroke Center St. Gallen, Switzerland

    Sankt Gallen

  • University Hospital, Stroke Center Zurich, Switzerland

    Zurich

Other trials in Switzerland

Germany2 sites
  • University Hospital, Stroke Center Charite Berlin, Germany

    Berlin

  • University Hospital, Stroke Center LMU Munich, Germany

    Munich

Other trials in Germany

Denmark1 site
  • University Hospital, Stroke Center Bispebjerg Hospital Copenhagen, Denmark

    Copenhagen

Other trials in Denmark

About this study

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.

Read the 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.
Being tested
Acetylsalicylic acid, Vitamin K antagonist

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Acetylsalicylic acidDrug

    Also called ASA

    Acetylsalicylic acid, 300mg o.p.d.

  • Vitamin K antagonistDrug

    Also called Phenprocoumon, Warfarin, Acenocoumarol

    Vitamin K-antagonists, target INR 2.0-3.0

Study groups in NCT02046460
Study groupRoleWhat they receive
Oral AnticoagulationActive comparatorVitamin K-Antagonists, target INR 2.0-3.0
Receives: Drug: Vitamin K antagonist
AntiplateletsExperimentalAcetylsalicylic acid, 300mg o.p.d.
Receives: Drug: Acetylsalicylic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary composite outcome measure - labeled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) -

    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.

    Measured: 3 months

Secondary outcomes (11)
  1. new ischemic strokes (including retinal infarction)

    Measured: 3 months

  2. new acute lesions on diffusion-weighted MRI

    Measured: 3 months

  3. any major extracranial hemorrhage

    Measured: 3 months

  4. any symptomatic intracranial hemorrhage

    Measured: 3 months

  5. any asymptomatic micro- or macrobleeds

    Measured: 3 months

  6. any death

    Measured: 3 months

  7. any increase in volume of the vessel wall hematoma at the followup cervical MRI as compared to the baseline MR-scan

    Measured: 3 months

  8. independence in activity of daily living (modified Rankin scale 0-2) at 3 months and at 6 months

    Measured: 3 months

  9. excellent functional outcome (modified Rankin scale 0,1) at 3 month and at 6 months

    Measured: 3 months

  10. any TIA (classical definition)

    Measured: 3 months

  11. recurrent cervical artery dissection

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2014 (estimated)
  2. Study startSep 2013
  3. Primary completionJun 2019
  4. Study completionJun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
194 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02046460
Sponsor's protocol ID
340/12
Acronym
TREAT-CAD
Status last verified
May 2024
First submitted
23 Jan 2014
Last updated
21 May 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Traenka C, Gensicke H, Schaedelin S, Luft A, Arnold M, Michel P, Kagi G, Kahles T, Nolte CH, Kellert L, Rosenbaum S, Sztaizel R, Brehm A, Stippich C, Psychogios M, Lyrer P, Engelter ST; TREAT-CAD investigators. Biomarkers and antithrombotic treatment in cervical artery dissection - Design of the TREAT-CAD randomised trial. Eur Stroke J. 2020 Sep;5(3):309-319. doi: 10.1177/2396987320921151. Epub 2020 Jun 29.

    PubMed 33072885
  • Engelter ST, Traenka C, Gensicke H, Schaedelin SA, Luft AR, Simonetti BG, Fischer U, Michel P, Sirimarco G, Kagi G, Vehoff J, Nedeltchev K, Kahles T, Kellert L, Rosenbaum S, von Rennenberg R, Sztajzel R, Leib SL, Jung S, Gralla J, Bruni N, Seiffge D, Feil K, Polymeris AA, Steiner L, Hamann J, Bonati LH, Brehm A, De Marchis GM, Peters N, Stippich C, Nolte CH, Christensen H, Wegener S, Psychogios MN, Arnold M, Lyrer P; TREAT-CAD investigators. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial. Lancet Neurol. 2021 May;20(5):341-350. doi: 10.1016/S1474-4422(21)00044-2. Epub 2021 Mar 23.

    PubMed 33765420
  • Engelter ST, Enz LS, Ravanelli F, Kaufmann JE, Gensicke H, Schaedelin S, Luft AR, Globas C, Goeggel-Simonetti B, Fischer U, Strambo D, Kagi G, Nedeltchev K, Kahles T, Kellert L, Rosenbaum S, von Rennenberg R, Brehm A, Seiffge D, Renaud S, Brandt T, Sarikaya H, Zietz A, Wischmann J, Polymeris AA, Fischer S, Bonati LH, De Marchis GM, Peters N, Nolte CH, Christensen H, Wegener S, Psychogios MN, Arnold M, Lyrer P, Traenka C. The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection. Eur Stroke J. 2025 Sep;10(3):871-881. doi: 10.1177/23969873251315362. Epub 2025 Feb 5.

    PubMed 39910883

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Acetylsalicylic acid and Vitamin K antagonist in people with Cervical Artery Dissection, run by Stefan Engelter at 10 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Switzerland, Germany, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary composite outcome measure - labeled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) - (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02046460, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024.

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