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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02046460
Recruitment Status : Recruiting
First Posted : January 27, 2014
Last Update Posted : January 8, 2019
University Hospital Inselspital, Berne
University of Lausanne Hospitals
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
The primary objective is to demonstrate the non-inferiority of treatment with ASA to anti-coagulant treatment with vitamin K antagonists in patients after a cervical artery dissection (CAD).

Condition or disease Intervention/treatment Phase
Cervical Artery Dissection Drug: Acetylsalicylic acid Drug: vitamin K-antagonist Phase 4

Detailed Description:

This is a randomized controlled, open labeled multicenter, non-inferiority trial with blinded assessment of outcome events. Implementation of this study is planned at Swiss Stroke Centers or Units.

Identical investigations will be performed in all patients eligible to participate in this study.

Imaging: For verification of CAD diagnosis, all study participants will undergo a standardized routine MRI scan of brain and neck before study entry. 14 +/- 7 days after treatment onset a second MRI of brain and neck will be performed. The following MRI sequences will be performed on a 3 Tesla scanner (1) spin echo (SE) T1w, turbo spin-echo (TSE) T2w, FLAIR to detect chronic ischemic brain lesions. (2) Diffusion weighted imaging (DWI) including apparent diffusion coefficient (ADC) maps to detect acute ischemic brain lesions. (3) susceptibility-weighted imaging (SWI) sequences or T2*w gradient echo (GRE) to detect hemorrhagic brain lesions (4) contrast-enhanced magnetic resonance angiography (CE-MRA) to improve delineation of the wall hematoma against the perfused vessel lumen, and to assess the degree of obstruction of the affected artery. MRI scans will be centrally analysed at the University Hospital Basel, and independently assessed by two observers who are blinded to the type of treatment and clinical outcome.

Clinical examination: Patients will be examined clinically by a neurologist at the screening visit, at the randomization visit, 14 +/- 7 days after randomization, at 3 months and at 6 months after randomization. At each visit, clinical outcome events will be assessed, focal neurological deficit measured using the National Institutes of Health (NIH) Stroke Scale,12 and functional level of independence using the modified Rankin Scale13. Clinical outcome events will be independently adjudicated in the coordinating center Basel, blinded to the type of treatment.

Blood sampling for biomarkers analyses will be done at two times; the first as soon as possible after verification of CAD-diagnosis and the second 14 +/- 7 days after treatment onset. Measured biomarkers include: MMP9 and TIMP2. The biomarkers will be analysed with multiplex electrochemiluminescent immunosorbent assays .

Treatment allocation: Patients will be randomized to receive either Aspirin (ASA) or anticoagulants (ratio 1:1). ASA means Aspirin™ 300 mg q.d. given orally. In patients who cannot swallow safely, ASA will be given intravenously (e.g. Aspegic™ 250 mg q.d.) until swallowing function has recovered. Anticoagulants mean the use of vitamin K antagonists (i.e., phenprocoumon [Marcoumar™] or acenocoumarol [Sintrom™]) with a target international normalized ratio (INR) of 2.0 - 3.0. Until the target INR has been reached, patients will receive anticoagulation with i.v. heparin or low molecular weight heparin). The choice of the distinct agent (e.g. phenprocoumon or acenocoumarol) can be chosen by the treating physician and the patient, taking into account the experience with these agents (phenprocoumon is more commonly used in the German speaking part, acenocoumarol is usually used in the French speaking part of Switzerland). Treatment should start as soon as diagnosis has been established, informed consent by patients or next-to-kin was obtained and baseline magnetic resonance (MR)-images have been performed (maximum time window maximum 24 hours). Treatment duration will be 90 days +/-14 days (i.e., until the follow-visit 2).

Miscellaneous: The patients will be asked to allow the usage of anonymous study data for possible individual patient data meta-analyses in the future in case of other randomized clinical trials (RCT) studying the same subject will become available.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 169 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection - TREAT-CAD
Study Start Date : September 2013
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin K
Drug Information available for: Menadione

Arm Intervention/treatment
Active Comparator: antithrombotic treatment
acetylsalicylic acid, 300mg o.p.d.
Drug: Acetylsalicylic acid
acetylsalicylic acid, 300mg o.p.d.
Other Name: ASA

Experimental: oral anticoagulation
vitamin K-antagonist, dosage according to INR 2.0-3.0
Drug: vitamin K-antagonist
vitamin K-antagonist, dosage according to INR 2.0-3.0
Other Name: Marcoumar

Primary Outcome Measures :
  1. 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: (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 macro bleeds, (iii) death.

Secondary Outcome Measures :
  1. New ischemic strokes; any symptomatic intracranial bleeds; any asymptomatic bleeds; any death; any increase in vessel wall hematoma; magnetic resonance spectroscopy (mRS) 0-2; mRS 0-1; any transient ischemic attack (TIA) [ Time Frame: 3 months ]
  2. new acute DWI lesions [ Time Frame: 3 months ]
  3. any major extracranial bleeds [ Time Frame: 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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" 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02046460

Contact: Stefan T. Engelter, MD

University Hospital Basle, Stroke Center Basle Recruiting
Basle, BS, Switzerland, 4031
Contact: Stefan T. Engelter, MD         
Principal Investigator: Stefan T. Engelter, MD         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
University Hospital Inselspital, Berne
University of Lausanne Hospitals
Principal Investigator: Stefan T. Engelter, MD University Hospital Basle Switzerland Stroke Center

Responsible Party: University Hospital, Basel, Switzerland Identifier: NCT02046460     History of Changes
Other Study ID Numbers: 340/12
First Posted: January 27, 2014    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019

Additional relevant MeSH terms:
Aneurysm, Dissecting
Vascular Diseases
Cardiovascular Diseases
Vitamin K
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors