Clinical trial NCT02841098: " Endarterectomy Combined With Optimal Medical Therapy (OMT) vs OMT Alone in Patients With Asymptomatic Severe Atherosclerotic Carotid Artery Stenosis at Higher-than-average Risk of Ipsilateral Stroke "
Official title: " Endarterectomy Combined With Optimal Medical Therapy Versus Optimal Medical Therapy Alone in Patients With Asymptomatic Severe Atherosclerotic Carotid Artery Stenosis at Higher-than-average Risk of Ipsilateral Stroke "
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asymptomatic Carotid Artery Stenosis
Keywords: Carotid stenosis,stroke,endarterectomy,medical therapy
Lead sponsor: Centre Hospitalier St Anne
Sponsor class: OTHER
Collaborators: name: Hôpitaux Universitaires Paris Ile-de-Franc Ouest
First posted: 2016-07-22
Enrollment: 43
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether carotid surgery combined with optimal medical therapy improves long-term survival free of ipsilateral stroke in patients with asymptomatic carotid stenosis at higher-than-average risk of ipsilateral stroke when compared with optimal medical therapy alone.

Detailed description: Carotid artery stenosis \>= 50% affects about 3% of subjects \>= 60 years and accounts for up to 15% of all ischemic strokes. Overall, patients with asymptomatic carotid stenosis have a low risk of ipsilateral stroke on modern medical therapy. It is therefore uncertain whether the benefit of carotid surgery still justifies the perioperative risk of stroke or death, and whether revascularisation is good value for money considering competing demands on health services. Several imaging techniques have been developed to identify patients with asymptomatic carotid stenosis at higher-than-average risk of ipsilateral stroke. Specifically, the presence of transcranial Doppler (TCD)-detected embolic signals, intraplaque haemorrhage on magnetic resonance imaging, TCD-measured impaired cerebral vasomotor reserve or rapid stenosis progression have all been shown to involve an at least 3-fold higher risk of ipsilateral stroke. However, before recommendations for clinical practice can be made regarding the use of these tools, their utility must be demonstrated in a formal randomised clinical trial. Our hypothesis is that the use of these predictors can identify a subset of patients with asymptomatic carotid stenosis who could benefit from prophylactic endarterectomy.

Carotid endarterectomy The procedure will be carried out with the technique routinely used by each surgeon. Operative reports and perioperative complications will be collected. CEA will have to be performed as soon as possible, within 60 days after randomization.

Optimal medical therapy OMT will be applied to all patients and started immediately after randomisation.

OMT will be defined by the adhoc committee and follow relevant guidelines. It will include:

* Antiplatelet therapy. If the patient requires anticoagulation for any reason (e.g. atrial fibrillation), the patient should be treated with an appropriate anticoagulant according to the practice at the centre as an alternative to antiplatelet therapy.
* Antihypertensive treatment, if required, to achieve a target blood pressure \< 140/90 mmHg (higher targets may be defined by the OMT committee for selected conditions, e.g. contralateral carotid occlusion) Application of structured programs, such as stepped-care approach using ranking of antihypertensive drugs will be used.
* High-dose statin treatment (target LDL \< 0.7 g/l). A stepped-care approach with raking of lipid-lowering drugs will also be used.
* Patients smoking at the time of randomisation will be encouraged to stop and join a smoking cessation and support program.
* Other lifestyle modification: reduction of alcohol consumption, choosing healthy food, increasing regular physical activity, reduction of body weight if relevant.

OMT may be modified during the course of the trial to take account revised guidelines or new evidence.

Eligibility criteria: Inclusion Criteria:

* Age 50 years or over
* No ipsilateral stroke or TIA within 180 days of randomization
* Atherosclerotic carotid stenosis between 70 and 99% (NASCET method)
* At least one of the following markers of ipsilateral stroke risk:

  * Silent brain infarction on MRI, DWi, consistent with embolism from or hemodynamic consequences of the qualifyiing stenosis
  * History of contralateral TIA or ischemic stroke due to atherosclerotic carotid disease
  * Predominantly echolucent plaque on ultrasound
  * Rapid (within 1 year) carotid stenosis progresion
  * TCD-detected microembolic signals
  * Impairment of TCD-measured cerebral vasomotor reserve
  * Intraplaque haemorrhage on magnetic resonance imaging
  * Rapid and severe stenosis progression
* Patient is able and willing to give informed consent

Exclusion Criteria:

* Previous revascularization procedure in the artery to be randomised
* Patients not suitable for endarterectomy due to anatomical factors
* Carotid stenosis caused by non-atherosclerotic disease e.g. neck radiotherapy or fibromuscular disease
* Patients who have had contralateral carotid artery or vertebral artery or intracranial artery revascularisation within 6 weeks prior to randomisation
* Patients with planned revascularisation of the contralateral carotid artery or a vertebral artery or an intracranial artery within 6 weeks after randomisation or the date of CEA
* Patients who have had coronary artery bypass grafting within 3 months prior to randomisation or other major surgery within 6 weeks prior to randomisation
* Patients with planned coronary artery bypass grafting or other major surgery within 6 weeks after CEA of the artery considered for treatment in the trial
* Patients with pre-existing disability (modified Rankin score greater than 2)
* Patients who have a low 5-year life expectancy (see appendix for definition)
* Patients intolerant or allergic to all of the medications available for OMT
* Patients in clinical trials of investigational medicinal products or who have been in clinical trials within the last 4 months will not be enrolled unless otherwise agreed
* Patients who are known to be pregnant
* Patients unwilling or unable to participate in follow-up

Primary outcomes:
measure: Ipsilateral stroke or procedural stroke or death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary outcomes:
measure: Any stroke or procedural death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Any disabling or fatal stroke or procedural death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Any stroke or TIA or procedural death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Any stroke or death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Myocardial infarction
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Any death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Cardiovascular death
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Any hospitalisation for vascular disease
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Cranial nerve palsy attributed to revascularisation
timeFrame: M1
measure: Haematoma caused by treatment requiring surgery, transfusion or prolonging hospital stay
timeFrame: M1
measure: Further revascularisation of the randomised artery after the initial attempt.
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: Carotid revascularisation
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
measure: New cerebral infarction or haemorrhage
timeFrame: M24
measure: Increase in white-matter changes
timeFrame: M0, M24
measure: Cognitive impairment
timeFrame: M0, M24
measure: Depression
timeFrame: M0, M24
measure: Health-related quality of life
timeFrame: M0, M24
measure: Disability
timeFrame: M0, M24
measure: Achievement of goals for each of the components of optimal medical treatment
timeFrame: M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Other outcomes:
Locations:
city: Besançon
country: France
facility: Centre Hospitalier régional de Besançon, Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: CHU Bordeaux, Groupe Hospitalier Pellegrin
city: Brest
country: France
facility: CHRU La Cavale Blanche
city: Clermont-ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Creteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHU Dijon-Bourgogne
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Chesnay
country: France
facility: Hôpital Mignot - CH Versailles
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hôpital Neurologique Pierre Wertheimer GHE
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Nice
country: France
facility: CHU de Nice, Hôpital Pasteur 2
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpétrière
city: Paris
country: France
facility: Centre Hospitalier Sainte-Anne
city: Paris
country: France
facility: Centre Hospitalier Bichat-Claude Bernard
city: Poitiers
country: France
facility: CHU La Milétrie
city: Rennes
country: France
facility: Hôpital Pontchaillou CHU Rennes
city: Rouen
country: France
facility: CHU de Rouen, Hôpital Charles Nicolle
city: Saint-etienne
country: France
facility: Hôpital Nord CHU Saint-Etienne
city: Strasbourg
country: France
facility: CHU de Strasbourg, Hôpital de Hautpierre
city: Toulouse
country: France
facility: CHU de Toulouse Hôpital Pierre-Paul Riquet
Study officials:
affiliation: CHSA
name: Jean-Louis MAS
role: STUDY_DIRECTOR
References: