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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University Hospital, Basel, Switzerland
Sponsor:
Collaborators:
University Hospital Inselspital, Berne
CHUV, Lausanne, Switzerland
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT02046460
First received: January 23, 2014
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Cervical Artery Dissection
Drug: Acetylsalicylic acid
Drug: vitamin K-antagonist
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection - TREAT-CAD

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
  • new acute DWI lesions [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • any major extracranial bleeds [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 169
Study Start Date: September 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: antithrombotic treatment
acetylsalicylic acid, 100mg o.p.d.
Drug: Acetylsalicylic acid
acetylsalicylic acid, 100mg 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02046460

Contacts
Contact: Stefan T. Engelter, MD stefan.engelter@usb.ch

Locations
Switzerland
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
CHUV, Lausanne, Switzerland
Investigators
Principal Investigator: Stefan T. Engelter, MD University Hospital Basle Switzerland Stroke Center
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02046460     History of Changes
Other Study ID Numbers: 340/12
Study First Received: January 23, 2014
Last Updated: August 19, 2014
Health Authority: Switzerland: Swissmedic

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

ClinicalTrials.gov processed this record on November 20, 2014