Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT00238667 |
Other study ID # |
CAMER5UA |
Secondary ID |
2006-002827-1804 |
Status |
Completed |
Phase |
Phase 3
|
First received |
October 11, 2005 |
Last updated |
May 19, 2015 |
Start date |
November 2005 |
Est. completion date |
May 2014 |
Study information
Verified date |
September 2005 |
Source |
St George's, University of London |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
United Kingdom: Research Ethics Committee |
Study type |
Interventional
|
Clinical Trial Summary
This is a feasibility study to determine if a sufficient number of patients can be recruited
throughout the United Kingdom and whether sufficient endpoints can be generated for a full
scale therapeutic trial of anticoagulants versus antiplatelets in acute cervical artery
dissection treatment.
Description:
ST. GEORGE'S HEADED NOTEPAPER
CADISS FEASIBILITY STUDY (Cervical Artery Dissection in Stroke Study) PROTOCOL
Aim:
To determine the feasibility of a clinical trial comparing antiplatelet therapy with
anticoagulation in the acute treatment of patients with cervical artery dissection.
Specifically to address whether:
1. There are sufficient clinical endpoints to provide the power to determine treatment
effect;
2. Adequate numbers of patients can be recruited.
Dissection of the carotid and vertebral arteries is a major cause of stroke in persons < 50
years of age, mainly due to embolism from clot sealing the tear. At present physicians treat
these patients with anticoagulants or antiplatelet drugs to prevent further stroke, but
neither therapy is evidence-based. Anticoagulants may be powerful anti-embolic agents but
are also more dangerous than aspirin, and potentially could encourage further dissection.
Most published studies are flawed by retrospective data, with no reference to the number of
patients in the original study cohort and do not include the critical principles of
randomisation and 'blinding'.
Proposal of present 'feasibility'study:
The only prospective data available (1) suggest that anticoagulants are more effective than
antiplatelet agents in reducing further TIA and stroke after dissection, but the numbers
were small and lack reliable statistical confirmation. This study was not a randomised
controlled trial and therefore may be open to bias in selection of treatment. As well, it
found that most recurrent events occur within the first month and thereafter the number
tails off. A total of about 1800 patients for a two armed therapeutical trial was necessary
to be calculated on these data.
Authors of a previous Cochrane review (2) reviewing available published literature
calculated that a total of about 2000 patients (1000 in each treatment arm) is needed for a
blinded randomised trial of anticoagulants versus antiplatelet agents. This would need a
major, probably international, study involving over 50 centres, and would be an expensive
undertaking. Prior to starting such a study it is important to determine whether this would
be feasible. This is particularly important for carotid and vertebral dissection which is a
frequently missed diagnosis, at least during the acute phase. Limited natural history
outcome data suggest the risk of recurrent stroke and TIA following carotid and vertebral
dissection is only markedly raised during the first week to month (1, 3) and therefore early
identification and recruitment of patients are essential if any treatment effect is to be
demonstrated.
For these reasons, a feasibility study is essential before any large scale clinical trial.
Specifically, two things need to be determined. Firstly, whether a sufficient number of
patients can be recruited sufficiently early from participating centres. Secondly, in view
of the limited data on the rate of recurrent TIA and stroke in patients with recent
dissection, we need more data to obtain a robust estimate of early risk to inform power
calculations for a large scale study.
A preliminary informal survey conducted by Clinical Neurosciences, St. George's University
of London, in association with the Association of British Neurologists, has indicated that
at least 27 neurologists/stroke physicians throughout the UK would be interested in
collaborating and enrolling consecutive consenting patients into such a study comparing
anticoagulation or antiplatelet therapy.
Methods:
This will be a randomised multicentre single blind study comparing antiplatelet therapy with
anticoagulation for patients with carotid and vertebral dissection. Recruitment must be
within seven days of onset of symptoms.
Inclusion Criteria:
1. Extracranial carotid or vertebral artery dissection with symptom onset within the last
7 days. This includes:
1. Ipsilateral TIA or stroke
2. Ipsilateral Horner's syndrome or neck pain with known date of onset
2. Imaging evidence of definite or probable dissection on magnetic resonance imaging
(MRI)/magnetic resonance angiography (MRA), computed tomography angiography (CTA) or
ultrasound (patients can be initially randomised on ultrasound alone but subsequent MR
or CTA confirmation is needed)
Exclusion Criteria:
1. Intracranial cerebral artery dissection
2. Symptom onset after 7 days
3. Contraindications to either antiplatelet agents or anticoagulation therapy
4. Patient refusal to consent
5. Patients who are undergoing angioplasty and stenting or surgery for treatment of their
dissection
Treatment:
Patients will be randomised to either antiplatelet or anticoagulation therapy allocated on a
single blind basis and continued for six months.
1. Antiplatelet therapy: Aspirin 75-300 mg daily, aspirin and dipyridamole or clopidogrel
alone
2. Anticoagulation with heparin (either unfractionated heparin or a therapeutic dose of
low molecular weight heparin) followed by warfarin aiming for an INR in the range
2.5-4. Local protocols for heparin therapy can be used.
Primary Endpoint:
Ipsilateral stroke, transient ischaemic attack or vascular death within 6 months from
randomisation
Secondary Endpoint:
1. TIA and stroke in other cerebral vascular territories
2. Recanalisation on repeat imaging at 6 months.
Imaging Protocol:
The diagnosis of dissection is based on different modalities in different centres. Centres
should use their usual imaging protocol to diagnose dissection. Diagnosis on the basis of
MRI with cross-sectional imaging through the artery wall, MRA, CT angiography,
intra-arterial angiography, and ultrasound (later confirmed by MR or CTA) are all
acceptable.
Patients can be randomised if the HQ radiologist (Dr. Clifton) agrees that the diagnosis is
probable or definite. Hard copies of imaging must be recorded for central reading.
The primary analysis will include only those patients judged to have probable or definite
dissection on central reading of the hard copies.
Randomisation:
Randomisation will be via 24 hour randomisation service provided by the University of
Aberdeen Health Services Research Unit.
The local investigator will personally contact this service at 0800 387 4444 and the Centre
will give the investigator a code number, known only to the randomisation centre and local
investigator.
Trial Management:
The study will be coordinated from Clinical Neuroscience at St. George's, University of
London. The principal co-investigators are Professor John Norris and Professor Hugh Markus.
The principal neuroradiological investigator, responsible for assessment of hard copies of
imaging, is Dr Andrew Clifton. The trial will be coordinated by a clinical fellow funded by
a project grant from The Stroke Association.
References
1. Beletsky V, Nadareishvili Z, Lynch J, Shuaib A, Woolfenden A, Norris JW; Canadian
Stroke Consortium (2003) Cervical Arterial Dissection; Time for a Therapeutic Trial?
Stroke Dec; 34(12)2856-60
2. Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. Cochrane
Review Oxford,UK. Cochrane Library 2002. Issue 1
3. Biousse V, D'Anglejan-Chatillon J, Touboul PJ, Amarenco P, Bousser MG (1995) Timecourse
of Symptoms in Extracranial Carotid Artery Dissections. A Series of 80 patients Stroke
Feb; 26(2)