" 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 " (ACTRIS)

" 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 "

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Asymptomatic Carotid Artery Stenosis
• Intervention / Treatment: Other: Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT); Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 700
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Louis MAS, MD; Phone Number: 00 33 1 45 65 82 84; Email: jl.mas@ch-sainte-anne.fr
• Study Contact Backup: Name: Sylvie DOROCANT; Phone Number: 00 33 1 45 65 77 28; Email: s.dorocant@ghu-paris.fr

Study Locations

• France
  • Besançon, France, 25030
    • Centre Hospitalier régional de Besançon, Hôpital Jean Minjoz
    • Contact: Thierry MOULIN, MD, PhD; Phone Number: 00 33 3 81 66 84 38; Email: thierry.moulin@univ-fcomte.fr
  • Bordeaux, France, 33076
    • CHU Bordeaux, Groupe Hospitalier Pellegrin
    • Contact: Igor SIBON, MD, PhD; Phone Number: 00 33 5 56 79 55 20; Email: igor.sibon@chu-bordeaux.fr
  • Brest, France, 29200
    • CHRU La Cavale Blanche
    • Contact: Serge TIMSIT, MD, PhD; Phone Number: 00 33 2 98 34 73 00; Email: serge.timsit@chu-brest.fr
  • Clermont-ferrand, France, 63003
    • Hôpital Gabriel Montpied
    • Contact: Pierre CLAVELOU, MD, PhD; Phone Number: 00 33 4 73 75 22 02; Email: pclavelou@chu-clermontferrand.fr
  • Creteil, France, 94010
    • CHU Henri Mondor
  • Dijon, France, 21079
    • Chu Dijon-Bourgogne
    • Contact: Maurice GIROUD, MD, PhD; Phone Number: 00 33 3 80 29 37 53; Email: maurice.giroud@chu-dijon.fr
  • Grenoble, France, 38043
    • CHU de Grenoble
    • Contact: Olivier DETANTE, MD; Phone Number: 00 33 4 76 76 57 89; Email: odetante@chu-grenoble.fr
  • Le Chesnay, France, 78150
    • Hôpital Mignot - CH Versailles
    • Contact: Fernando PICO, MD, PhD; Phone Number: 00 33 1 39 63 95 17; Email: fpico@ch-versailles.fr
  • Lille, France, 59037
    • CHRU de Lille
    • Contact: Hilde HENON, MD; Phone Number: 00 33 3 20 44 68 14; Email: hilde.henon@chru-lille.fr
  • Lyon, France, 69677
    • Hôpital Neurologique Pierre Wertheimer GHE
    • Contact: Norbert NIGHOGHOSSIAN, MD, PhD; Phone Number: 00 33 4 72 35 78 10; Email: Norbert.nighoghossian@chu-lyon.fr
  • Montpellier, France, 34 295
    • Hopital Gui de Chauliac
    • Contact: Caroline ARQUIZAN, MD; Phone Number: 00 33 4 67 33 74 12; Email: c-arquizan@chu-montpellier.fr
  • Nice, France, 06000
    • CHU de Nice, Hôpital Pasteur 2
    • Contact: Marie-Hélène MAHAGNE, MD; Phone Number: 00 33 4 92 03 27 51; Email: mahagne.h@chu-nice.fr
  • Paris, France, 75012
    • Hopital Saint-Antoine
    • Contact: Sonia ALAMOWITCH, MD, PhD; Phone Number: 00 33 1 71 97 06 51; Email: sonia.alamowitch@aphp.fr
  • Paris, France, 75010
    • Hopital Lariboisiere
    • Contact: Hugues CHABRIAT, MD, PhD; Phone Number: 00 33 1 49 95 25 97; Email: hugues.chabriat@aphp.fr
  • Paris, France, 75014
    • Centre Hospitalier Sainte-Anne
    • Contact: Jean-Louis MAS, MD, PhD; Phone Number: 00 33 1 45 65 82 84; Email: jl.mas@ch-sainte-anne.fr
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpetriere
    • Contact: Yves SAMSON, MD, PhD; Phone Number: 00 33 1 42 16 18 54; Email: yves.samson@aphp.fr
  • Paris, France, 75018
    • Centre Hospitalier Bichat-Claude Bernard
    • Contact: Pierre AMARENCO, MD, PhD; Phone Number: 00 33 1 40 25 87 26; Email: pierre.amarenco@aphp.fr
  • Poitiers, France, 86021
    • CHU La Milétrie
    • Contact: Jean-Philippe NEAU, MD, PhD; Phone Number: 00 33 5 49 44 44 46; Email: jph.neau@chu-poitiers.fr
  • Rennes, France, 35033
    • Hôpital Pontchaillou CHU RENNES
    • Contact: Jean-François PINEL, MD; Phone Number: 00 33 2 99 28 42 93; Email: jf.pinel@chu-rennes.fr
  • Rouen, France, 76031
    • CHU de Rouen, Hopital Charles Nicolle
    • Contact: Evelyne GUEGAN MASSARDIER, MD; Phone Number: 00 33 2 32 88 67 86; Email: evelyne.massardier@chu-rouen.fr
  • Saint-etienne, France, 42055
    • Hôpital Nord CHU Saint-Etienne
    • Contact: Pierre GARNIER, MD; Phone Number: 00 33 4 77 12 78 05; Email: pierre.garnier@chu-st-etienne.fr
  • Strasbourg, France, 67098
    • CHU de Strasbourg, Hôpital de Hautpierre
    • Contact: Valérie WOLFF, MD; Phone Number: 00 33 3 88 12 86 06; Email: valerie.wolff@chru-strasbourg.fr
  • Toulouse, France, 31059
    • CHU de Toulouse Hôpital Pierre-Paul Riquet
    • Contact: Vincent LARRUE, MD, PhD; Phone Number: 00 33 5 61 77 94 57; Email: larrue.v@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carotid endarterectomy combined with optimal medical therapy; Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT)	Other: Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT); Carotid endarterectomy (CEA) combined with optimal medical therapy (OMT) (Surgery and Drug)
Active Comparator: Optimal medical therapy (OMT)	Drug: Optimal medical therapy alone; Optimal medical therapy alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Myocardial infarction	Myocardial infarction within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Any death	Any death within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
Cardiovascular death	Cardiovascular death within 6 years after randomization	M1, M6, M12, M18, M24, M30, M36, M42, M48, M54, M60, M66, M72
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
Cranial nerve palsy attributed to revascularisation	Cranial nerve palsy attributed to revascularisation within 30 days after revascularization	M1
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
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
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
New cerebral infarction or haemorrhage	New cerebral infarction or haemorrhage on MRI at 2 years	M24
Increase in white-matter changes	Increase in white-matter changes on MRI at 2 years.	M0, M24
Cognitive impairment	Cognitive impairment assessed by the Montreal Cognitive Assessment (MoCA) with adjustment for demographic factors.	M0, M24
Depression	Depression measured by the Centre for Epidemiologic Studies Depression (CES-D) Scale.	M0, M24
Health-related quality of life	Health-related quality of life measured using the European Quality Of Life (EQ-5D).	M0, M24
Disability	Disability measured by the modified Rankin scale with structured interview	M0, M24
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

Collaborators and Investigators

• Sponsor: Centre Hospitalier St Anne
• Collaborators: Hôpitaux Universitaires Paris Ile-de-Franc Ouest
• Investigators: Study Director: Jean-Louis MAS, CHSA

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (Estimate): July 22, 2016

Study Record Updates

• Last Update Posted (Actual): July 1, 2019
• Last Update Submitted That Met QC Criteria: June 27, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Carotid stenosis,stroke,endarterectomy,medical therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Carotid Artery Diseases; Carotid Stenosis; Constriction, Pathologic
• Other Study ID Numbers: D15-P010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No