- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02046460
Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection - TREAT-CAD (TREAT-CAD)
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
Status
Conditions
Intervention / Treatment
Detailed Description
Substudies:
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.
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.
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.
- 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).
- 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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Copenhagen, Denmark
- University Hospital, Stroke Center Bispebjerg Hospital Copenhagen, Denmark
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Berlin, Germany
- University Hospital, Stroke Center Charite Berlin, Germany
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Munich, Germany
- University Hospital, Stroke Center LMU Munich, Germany
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Aarau, Switzerland
- Kantonsspital, Stroke Center Aarau, Switzerland
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Basel, Switzerland
- University Hospital, Stroke Center Basel, Switzerland
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Berne, Switzerland
- University Hospital, Stroke Center Inselspital Berne, Switzerland
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Geneva, Switzerland
- University Hospital, Stroke Center Geneva, Switzerland
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Lausanne, Switzerland
- University Hospital, Stroke Center CHUV Lausanne, Switzerland
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St. Gallen, Switzerland
- Kantonsspital, Stroke Center St. Gallen, Switzerland
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Zurich, Switzerland
- University Hospital, Stroke Center Zurich, Switzerland
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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)
Study Plan
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 |
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Active Comparator: Oral Anticoagulation
Vitamin K-Antagonists, target INR 2.0-3.0
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Vitamin K-antagonists, target INR 2.0-3.0
Other Names:
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Experimental: Antiplatelets
Acetylsalicylic acid, 300mg o.p.d.
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Acetylsalicylic acid, 300mg o.p.d.
Other Names:
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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
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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.
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3 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
new ischemic strokes (including retinal infarction)
Time Frame: 3 months
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3 months
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new acute lesions on diffusion-weighted MRI
Time Frame: 3 months
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3 months
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any major extracranial hemorrhage
Time Frame: 3 months
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3 months
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any symptomatic intracranial hemorrhage
Time Frame: 3 months
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3 months
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any asymptomatic micro- or macrobleeds
Time Frame: 3 months
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3 months
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any death
Time Frame: 3 months
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3 months
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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
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3 months
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independence in activity of daily living (modified Rankin scale 0-2) at 3 months and at 6 months
Time Frame: 3 months
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3 months
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excellent functional outcome (modified Rankin scale 0,1) at 3 month and at 6 months
Time Frame: 3 months
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3 months
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any TIA (classical definition)
Time Frame: 3 months
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3 months
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recurrent cervical artery dissection
Time Frame: 3 months
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3 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Stefan T. Engelter, MD, University Hospital, Neurorehab. Felix Platter, University of Basel, Switzerland
Publications and helpful links
General 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Aneurysm
- Aortic Diseases
- Dissection, Blood Vessel
- Acute Aortic Syndrome
- Aortic Dissection
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Micronutrients
- Vitamins
- Anticoagulants
- Antifibrinolytic Agents
- Hemostatics
- Coagulants
- Aspirin
- Vitamin K
- Phenprocoumon
- Warfarin
- Acenocoumarol
Other Study ID Numbers
- 340/12
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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