" 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 "
- Conditions
- Asymptomatic Carotid Artery Stenosis
- Interventions
- Other: Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT)Drug: Optimal medical therapy alone
- Registration Number
- NCT02841098
- Lead Sponsor
- Centre Hospitalier St Anne
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Carotid endarterectomy combined with optimal medical therapy Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT) Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT) Optimal medical therapy (OMT) Optimal medical therapy alone Optimal medical therapy (OMT)
- Primary Outcome Measures
Name Time Method Ipsilateral stroke or procedural stroke or death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any ipsilateral stroke within 6 years after randomization or procedural (within 30 days after revascularization) stroke or death
- Secondary Outcome Measures
Name Time Method Further revascularisation of the randomised artery after the initial attempt. M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Further revascularisation of the randomised artery after the initial attempt.
Any stroke or procedural death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any stroke within 6 years after randomization or procedural death (within 30 days after revascularization)
Any stroke or death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any stroke or death within 6 years after randomization
Any disabling or fatal stroke or procedural death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any disabling or fatal stroke within 6 years after randomization or procedural death (within 30 days after revascularization)
Any stroke or TIA or procedural death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any stroke or TIA within 6 years after randomization or procedural death within 6 years after randomization
Myocardial infarction M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Myocardial infarction within 6 years after randomization
Any death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any death within 6 years after randomization
Depression M0, M24 Depression measured by the Centre for Epidemiologic Studies Depression (CES-D) Scale.
Cardiovascular death M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Cardiovascular death within 6 years after randomization
Cranial nerve palsy attributed to revascularisation M1 Cranial nerve palsy attributed to revascularisation within 30 days after revascularization
Carotid revascularisation M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Carotid revascularisation during follow-up other than that allocated at randomisation
Increase in white-matter changes M0, M24 Increase in white-matter changes on MRI at 2 years.
Cognitive impairment M0, M24 Cognitive impairment assessed by the Montreal Cognitive Assessment (MoCA) with adjustment for demographic factors.
Any hospitalisation for vascular disease M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Any hospitalisation for vascular disease within 6 years after randomization
Haematoma caused by treatment requiring surgery, transfusion or prolonging hospital stay M1 Haematoma caused by treatment requiring surgery, transfusion or prolonging hospital stay within 30 days after revascularization
New cerebral infarction or haemorrhage M24 New cerebral infarction or haemorrhage on MRI at 2 years
Health-related quality of life M0, M24 Health-related quality of life measured using the European Quality Of Life (EQ-5D).
Disability M0, M24 Disability measured by the modified Rankin scale with structured interview
Achievement of goals for each of the components of optimal medical treatment M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72 Achievement of goals for each of the components of optimal medical treatment
Trial Locations
- Locations (23)
Hôpital Mignot - CH Versailles
🇫🇷Le Chesnay, France
Centre Hospitalier Bichat-Claude Bernard
🇫🇷Paris, France
CHU de Strasbourg, Hôpital de Hautpierre
🇫🇷Strasbourg, France
CHU de Toulouse Hôpital Pierre-Paul Riquet
🇫🇷Toulouse, France
Hôpital Nord CHU Saint-Etienne
🇫🇷Saint-etienne, France
Centre Hospitalier régional de Besançon, Hôpital Jean Minjoz
🇫🇷Besançon, France
CHU Bordeaux, Groupe Hospitalier Pellegrin
🇫🇷Bordeaux, France
CHRU La Cavale Blanche
🇫🇷Brest, France
CHU Dijon-Bourgogne
🇫🇷Dijon, France
Hôpital Gabriel Montpied
🇫🇷Clermont-ferrand, France
CHU Henri Mondor
🇫🇷Creteil, France
CHU de Grenoble
🇫🇷Grenoble, France
Hôpital Neurologique Pierre Wertheimer GHE
🇫🇷Lyon, France
CHRU de Lille
🇫🇷Lille, France
Hôpital Gui de Chauliac
🇫🇷Montpellier, France
CHU de Nice, Hôpital Pasteur 2
🇫🇷Nice, France
Hôpital Lariboisière
🇫🇷Paris, France
Hôpital Saint-Antoine
🇫🇷Paris, France
Groupe Hospitalier Pitié-Salpétrière
🇫🇷Paris, France
Centre Hospitalier Sainte-Anne
🇫🇷Paris, France
CHU La Milétrie
🇫🇷Poitiers, France
CHU de Rouen, Hôpital Charles Nicolle
🇫🇷Rouen, France
Hôpital Pontchaillou CHU Rennes
🇫🇷Rennes, France