" 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 "

Asymptomatic Carotid Artery Stenosis Clinical Trial

— ACTRIS  

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 "

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02841098
• Other study ID #: D15-P010
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2019
• Est. completion date: December 2025

Study information

• Verified date: June 2019
• Source: Centre Hospitalier St Anne
• Contact: Jean-Louis MAS, MD
• Phone: 00 33 1 45 65 82 84
• Email: jl.mas[@]ch-sainte-anne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 700
• Est. completion date: December 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asymptomatic Carotid Artery Stenosis
• Carotid Stenosis
• Constriction, Pathologic

Intervention

Other:
• Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT)
Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT) (Surgery and Drug)

Drug:
• Optimal medical therapy alone
Optimal medical therapy alone

Locations

Country	Name	City	State
France	Centre Hospitalier régional de Besançon, Hôpital Jean Minjoz	Besançon
France	CHU Bordeaux, Groupe Hospitalier Pellegrin	Bordeaux
France	CHRU La Cavale Blanche	Brest
France	Hôpital Gabriel Montpied	Clermont-ferrand
France	CHU Henri Mondor	Creteil
France	CHU Dijon-Bourgogne	Dijon
France	CHU de Grenoble	Grenoble
France	Hôpital Mignot - CH Versailles	Le Chesnay
France	CHRU de Lille	Lille
France	Hôpital Neurologique Pierre Wertheimer GHE	Lyon
France	Hôpital Gui de Chauliac	Montpellier
France	CHU de Nice, Hôpital Pasteur 2	Nice
France	Centre Hospitalier Bichat-Claude Bernard	Paris
France	Centre Hospitalier Sainte-Anne	Paris
France	Groupe Hospitalier Pitié-Salpétrière	Paris
France	Hôpital Lariboisière	Paris
France	Hôpital Saint-Antoine	Paris
France	CHU La Milétrie	Poitiers
France	Hôpital Pontchaillou CHU Rennes	Rennes
France	CHU de Rouen, Hôpital Charles Nicolle	Rouen
France	Hôpital Nord CHU Saint-Etienne	Saint-etienne
France	CHU de Strasbourg, Hôpital de Hautpierre	Strasbourg
France	CHU de Toulouse Hôpital Pierre-Paul Riquet	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier St Anne	Hôpitaux Universitaires Paris Ile-de-Franc Ouest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ipsilateral stroke or procedural stroke or death	Any ipsilateral stroke within 6 years after randomization or procedural (within 30 days after revascularization) stroke or death	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Any stroke or procedural death	Any stroke within 6 years after randomization or procedural death (within 30 days after revascularization)	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Any disabling or fatal stroke or procedural death	Any disabling or fatal stroke within 6 years after randomization or procedural death (within 30 days after revascularization)	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Any stroke or TIA or procedural death	Any stroke or TIA within 6 years after randomization or procedural death within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Any stroke or death	Any stroke or death within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Myocardial infarction	Myocardial infarction within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Any death	Any death within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Cardiovascular death	Cardiovascular death within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Any hospitalisation for vascular disease	Any hospitalisation for vascular disease within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Cranial nerve palsy attributed to revascularisation	Cranial nerve palsy attributed to revascularisation within 30 days after revascularization	M1
Secondary	Haematoma caused by treatment requiring surgery, transfusion or prolonging hospital stay	Haematoma caused by treatment requiring surgery, transfusion or prolonging hospital stay within 30 days after revascularization	M1
Secondary	Further revascularisation of the randomised artery after the initial attempt.	Further revascularisation of the randomised artery after the initial attempt.	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	Carotid revascularisation	Carotid revascularisation during follow-up other than that allocated at randomisation	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Secondary	New cerebral infarction or haemorrhage	New cerebral infarction or haemorrhage on MRI at 2 years	M24
Secondary	Increase in white-matter changes	Increase in white-matter changes on MRI at 2 years.	M0, M24
Secondary	Cognitive impairment	Cognitive impairment assessed by the Montreal Cognitive Assessment (MoCA) with adjustment for demographic factors.	M0, M24
Secondary	Depression	Depression measured by the Centre for Epidemiologic Studies Depression (CES-D) Scale.	M0, M24
Secondary	Health-related quality of life	Health-related quality of life measured using the European Quality Of Life (EQ-5D).	M0, M24
Secondary	Disability	Disability measured by the modified Rankin scale with structured interview	M0, M24
Secondary	Achievement of goals for each of the components of optimal medical treatment	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