Carotid Artery StenosisPhase 2PRECISE-MRINCT02677545
Ticagrelor Versus Clopidogrel in Carotid Artery Stenting
A Phase 2 study testing Ticagrelor, Clopidogrel and Aspirin in people with Carotid Artery Stenosis, run by University Hospital, Basel, Switzerland at 15 sites in 6 countries.
Trial summary
Patients with symptomatic or asymptomatic carotid stenosis in whom carotid artery stenting is planned are randomised between antiplatelet therapy with ticagrelor plus aspirin or clopidogrel plus aspirin and examined with brain MRI before and after stent treatment. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Carotid Artery Stenosis
- What is being tested?
- Ticagrelor, Clopidogrel and Aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 15 sitesin 6 countries
- Study dates
- Dec 2016to 28 Apr 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent as documented by signature from the patient;
- Men or women ≥40 years of age;
- Moderate (50-69% narrowing of the artery according to the measuring method used in the NASCET trial64) or severe (70-99%) stenosis of the extracranial internal carotid artery caused by atherosclerosis;
- Symptomatic carotid stenosis (any transient or permanent symptoms caused by focal ischaemia in the vascular territory supplied by the carotid artery in the past 180 days, including ischaemic stroke, transient ischemic attack (TIA), amaurosis fugax or ischaemic retinal infarct), as long as the patient is clinically stable and able to walk unassisted (mRS ≤3) at the time of randomisation; or asymptomatic carotid stenosis (no ischaemic symptoms in the past 180 days);
- Stenosis amenable for treatment by CAS according to routine clinical work-up (degree of stenosis and suitability of vascular anatomy for CAS must be documented on vascular imaging within 90 days before the screening visit);
- CAS scheduled to take place within 1-3 days of randomisation.
Who cannot join
- Inability or unwillingness of the patient to understand and/or comply with study procedures and/or follow-up, e.g. due to language problems, psychological disorders, dementia, etc.;
- Women who are pregnant or breast feeding, or who intend to become pregnant during the course of the study. Women of childbearing age must take a blood pregnancy test to be eligible for the study within 14 days before randomisation;
- Lack of safe contraception, defined as: Female Participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the Investigator in individual cases. Female Participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential;
- Acute ischaemic stroke with symptom onset in the previous 24 hours before randomisation;
- atrial fibrillation;
- Fresh thrombus in the relevant carotid artery;
Show all 27Show fewer
- Patient clinically unstable at the time of randomisation (includes worsening in NIH Stroke Scale of >2 points over the previous 24 hours);
- Patient unable to walk unassisted at the time of randomisation (mRS >3);
- Patients with known bleeding diathesis or coagulation disorder (e.g., thrombotic-thrombocytopenic purpura);
- Any active pathological bleed;
- Severe thrombocytopenia (platelet count <50'000/uL); platelet count must be documented within 30 days before randomisation
- History of previous symptomatic intracranial haemorrhage at any time (asymptomatic microbleeds do not qualify)
- History of gastrointestinal bleed within the past 6 months;
- Any contraindication to non-contrast MRI, including but not limited to: cardiac pacemaker incompatible with MRI; metal implants incompatible with MRI; claustrophobia);
- Contraindications to ticagrelor, clopidogrel, or acetylsalicylic acid (ASA), or to any of their excipients, including known hypersensitivity or allergy;
- Increased risk of bradycardic events (e.g., patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block, or history of bradycardia-related syncope; ECG must be obtained within 30 days before randomisation
- Need for medication not permitted during treatment period: Antithrombotic therapy other than Study Medication or permitted concomitant medication (see section 8.7) including: Antiplatelet therapy (other than ASA 100 mg daily), e.g.: open-label clopidogrel or ticagrelor; GPIIb/GPIIIa inhibitors, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol; Therapeutic-dose anticoagulation (other than unfractioned heparin at the start of the CAS procedure), e.g.: phenprocoumon, warfarin, oral thrombin and factor Xa inhibitors, bivalirudin, hirudin, argatroban, unfractionated and low molecular weight heparins; Receipt of any intravenous or intra-arterial thrombolysis or mechanical thrombectomy within 24 hours prior to randomisation. If a patient requires intravenous or intra-arterial thrombolytic therapy during the treatment period, the Study Medication must be discontinued for at least 24 hours; Strong cytochrome P450 3A (CYP3A) inhibitors leading to substantial increases in ticagrelor plasma levels: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir; or consumption of more than 1 litre of grapefruit juice daily; Strong CYP3A inducers leading to substantial decreases in ticagrelor plasma levels: rifampicin, rifabutin, phenytoin, carbamazepine, and phenobarbital; CYP3A substrates with narrow therapeutic indices which may be substantially increased by co-administration of ticagrelor: cyclosporine, quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily. (Co-administration of ticagrelor with simvastatin increases simvastatin Cmax by 81% and area under curve (AUC) by 56% and increases simvastatin acid Cmax by 64% and AUC by 52% with some individual increases equal to 2- to 3-fold. Ticagrelor may have similar effect on lovastatin, but is not expected to have a clinically meaningful effect on other statins including atorvastatin and rosuvastatin); Anticipated requirement for long-term (>7 days) non-steroidal anti-inflammatory drugs (NSAIDs; short-term treatment with NSAIDs up to 7 days is allowed during the treatment period at the investigator's discretion);
- Need for any cardio-vascular surgery or cardio-vascular intervention other than the index CAS procedure for which the patient was randomised within the next 30 days after randomisation.
- Need for any other invasive procedure (surgery or intervention) other than the index CAS procedure for which the patient was randomised, which requires halting of Study Medication within the next 30 days after randomisation;
- History of major surgery within the past 30 days;
- Moderate or severe hepatic impairment;
- Renal impairment requiring dialysis;
- Known or suspected non-compliance, drug or alcohol abuse;
- Previous enrolment into the present study;
- Participation in another study with investigational drug within the 30 days preceding and during the present study;
- Patients incapable of judgment or patients under tutelage;
- Enrolment of the Investigator, his/her family members, employees and other dependent persons;
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Germany4 sites
University Hospital Aachen, Klinik für Diagnostische und Interventionelle Neuroradiologie
Aachen, 52074
Asklepios Kliniken Hamburg GmbH
Hamburg, 20099
Universitätsklinikum Heidelberg, Neurologische Klinik
Heidelberg, 69120
Universitätsklinikum Schleswig-Holstein
Kiel, 24105
Switzerland4 sites
Kantonsspital Aarau Klinik für Neurologie
Aarau, 5001
University Hospital Basel
Basel, 4031
Insel Gruppe AG, Department of Neurology
Bern, 3010
Stadtspital Triemli Zürich/Department of Cardiology
Zurich, 8063
Belgium2 sites
Ghent University Hospital - Dept thoracic and vascular surgery
Ghent, 9000
AZ Groeninge VZW
Kortrijk, 8500
Italy2 sites
Ospedale Civile di Mirano, Department of Cardiology
Mirano, 30035
UOC Neuroradiologia, Ospedale dell'Angelo
Venezia, 30174
Netherlands2 sites
AMC Medical Research BV on behalf of Academisch Medisch Centrum
Amsterdam, 1105
University Medical Center Utrecht
Utrecht, 3584
United Kingdom1 site
Sheffield Clinical Research Facility, Northern General Hospital
Sheffield, S57AU
About this study
Official title: Prevention of Cerebral Ischaemia in Stent Treatment for Carotid Artery Stenosis - A Randomised Multi-centre Phase II Trial Comparing Ticagrelor Versus Clopidogrel With Outcome Assessment on MRI (PRECISE-MRI)
Patients with symptomatic or asymptomatic carotid stenosis in whom carotid artery stenting is planned are randomised between antiplatelet therapy with ticagrelor plus aspirin or clopidogrel plus aspirin and examined with brain MRI before and after stent treatment. The proportion of patients with new ischaemic lesions on MRI after treatment is compared between the two groups.
Read the detailed description
Carotid artery stenting (CAS) is an emerging treatment for atherosclerotic carotid stenosis. The main adverse event is embolic stroke during the procedure. Current medical management to prevent peri-procedural embolisation consists of dual antiplatelet therapy with clopidogrel and aspirin. Ticagrelor, a novel reversible inhibitor of the platelet adenosine diphosphate receptor P2Y12, was superior to clopidogrel, as add-on therapy to aspirin, in preventing stent thrombosis, cardiovascular outcome events, and death in patients undergoing coronary artery stenting, without causing an increase in major bleeding events. This study aims to test the hypothesis that ticagrelor is superior to clopidogrel as add-on to aspirin in preventing cerebral embolism during the CAS procedure.
- Conditions
- Carotid Artery Stenosis
- Being tested
- Ticagrelor, Clopidogrel, Aspirin
- Medical subject headings
- Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Also called Brilique
ClopidogrelDrug
Also called Plavix
AspirinDrug
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor & Aspirin | Experimental | Participants will receive a loading dose of 180 mg ticagrelor 1-3 days before stenting followed by a maintenance dose of 90 mg twice daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period. Receives: Drug: Ticagrelor; Drug: Aspirin |
| Clopidogrel & Aspirin | Active comparator | Participants will receive a loading dose of 300 mg clopidogrel 1-3 days before stenting followed by a maintenance dose of 75 mg once daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period. Receives: Drug: Clopidogrel; Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
At least one new ischaemic brain lesion after CAS
The primary efficacy outcome is the presence of at least one new ischaemic brain lesion on the second MRI scan done 1-3 days after CAS or on the third MRI scan done 28-32 days after CAS, which had not been present on the first MRI scan done 1-3 days before CAS.
Measured: Up to 32 days after CAS
Secondary outcomes (4)
Composite of any stroke, myocardial infarction, major bleeding, or cardiovascular death
The clinical safety outcome is the composite of any stroke, myocardial infarction, major bleeding (including fatal, life-threatening or other major bleeding) or cardiovascular death occurring between randomisation and study completion.
Measured: Through study completion, an average of 1 month after randomisation
Number of new ischaemic brain lesions after CAS
A secondary efficacy outcome is the number of new ischaemic brain lesions on the second MRI scan done 1-3 days after CAS or on the third MRI scan done 28-32 days after CAS, which had not been present on the first MRI scan done 1-3 days before CAS.
Measured: Up to 32 days after CAS
Volume of new ischaemic brain lesions after CAS
A secondary efficacy outcome is the total volume of new ischaemic brain lesions on the second MRI scan done 1-3 days after CAS or on the third MRI scan done 28-32 days after CAS, which had not been present on the first MRI scan done 1-3 days before CAS.
Measured: Up to 32 days after CAS
At least one new haemorrhagic brain lesion after CAS
A secondary safety outcome is the presence of at least one new haemorrhagic brain lesion on the second MRI scan done 1-3 days after CAS or on the third MRI scan done 28-32 days after CAS, which had not been present on the first MRI scan done 1-3 days before CAS.
Measured: Up to 32 days after CAS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2016 (estimated)
- Study startDec 2016
- Primary completion28 Apr 2022
- Study completion28 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid Artery StenosisStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leo H Bonati, MD, Principal investigator, Department of Neurology and Stroke Center, University Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02677545
- Sponsor's protocol ID
- D5130C00171; me10Bonati
- Acronym
- PRECISE-MRI
- Status last verified
- Jun 2022
- First submitted
- 25 Jan 2016
- Last updated
- 28 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual participant data will be available for further analyses. Specific requests will be considered by the Trial Steering Committee.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Cerebral Ischaemia in Stent Treatment for Carotid Artery Stenosis - A Randomised Multi-centre Phase II Trial Comparing Ticagrelor Versus Clopidogrel With Outcome Assessment on MRI (PRECISE-MRI)
- ClinicalTrials.gov ID
- NCT02677545
- Acronym / sponsor ID
- PRECISE-MRI / D5130C00171; me10Bonati
- Conditions
- Carotid Artery Stenosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- 28 Apr 2022 (actual)
- Study completion
- 28 Apr 2022 (actual)
- First posted
- 9 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with symptomatic or asymptomatic carotid stenosis in whom carotid artery stenting is planned are randomised between antiplatelet therapy with ticagrelor plus aspirin or clopidogrel plus aspirin and examined with brain MRI before and after stent treatment. The proportion of patients with new ischaemic lesions on MRI after treatment is compared between the two groups.
Detailed description
Carotid artery stenting (CAS) is an emerging treatment for atherosclerotic carotid stenosis. The main adverse event is embolic stroke during the procedure. Current medical management to prevent peri-procedural embolisation consists of dual antiplatelet therapy with clopidogrel and aspirin. Ticagrelor, a novel reversible inhibitor of the platelet adenosine diphosphate receptor P2Y12, was superior to clopidogrel, as add-on therapy to aspirin, in preventing stent thrombosis, cardiovascular outcome events, and death in patients undergoing coronary artery stenting, without causing an increase in major bleeding events. This study aims to test the hypothesis that ticagrelor is superior to clopidogrel as add-on to aspirin in preventing cerebral embolism during the CAS procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor & Aspirin | Experimental | Drug: Ticagrelor, Drug: AspirinParticipants will receive a loading dose of 180 mg ticagrelor 1-3 days before stenting followed by a maintenance dose of 90 mg twice daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period. |
| Clopidogrel & Aspirin | Active comparator | Drug: Clopidogrel, Drug: AspirinParticipants will receive a loading dose of 300 mg clopidogrel 1-3 days before stenting followed by a maintenance dose of 75 mg once daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent as documented by signature from the patient;
- Men or women ≥40 years of age;
- Moderate (50-69% narrowing of the artery according to the measuring method used in the NASCET trial64) or severe (70-99%) stenosis of the extracranial internal carotid artery caused by atherosclerosis;
- Symptomatic carotid stenosis (any transient or permanent symptoms caused by focal ischaemia in the vascular territory supplied by the carotid artery in the past 180 days, including ischaemic stroke, transient ischemic attack (TIA), amaurosis fugax or ischaemic retinal infarct), as long as the patient is clinically stable and able to walk unassisted (mRS ≤3) at the time of randomisation; or asymptomatic carotid stenosis (no ischaemic symptoms in the past 180 days);
- Stenosis amenable for treatment by CAS according to routine clinical work-up (degree of stenosis and suitability of vascular anatomy for CAS must be documented on vascular imaging within 90 days before the screening visit);
Key exclusion criteria (27 listed)
- Inability or unwillingness of the patient to understand and/or comply with study procedures and/or follow-up, e.g. due to language problems, psychological disorders, dementia, etc.;
- Women who are pregnant or breast feeding, or who intend to become pregnant during the course of the study. Women of childbearing age must take a blood pregnancy test to be eligible for the study within 14 days before randomisation;
- Lack of safe contraception, defined as: Female Participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the Investigator in individual cases. Female Participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential;
- Acute ischaemic stroke with symptom onset in the previous 24 hours before randomisation;
- atrial fibrillation;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TicagrelorAlso: Brilique | Drug | Ticagrelor & Aspirin |
| ClopidogrelAlso: Plavix | Drug | Clopidogrel & Aspirin |
| Aspirin | Drug | Clopidogrel & Aspirin, Ticagrelor & Aspirin |
Primary outcome
At least one new ischaemic brain lesion after CAS
Time frame: Up to 32 days after CAS
The primary efficacy outcome is the presence of at least one new ischaemic brain lesion on the second MRI scan done 1-3 days after CAS or on the third MRI scan done 28-32 days after CAS, which had not been present on the first MRI scan done 1-3 days before CAS.
4 secondary outcomes
Composite of any stroke, myocardial infarction, major bleeding, or cardiovascular death
Time frame: Through study completion, an average of 1 month after randomisation
Number of new ischaemic brain lesions after CAS
Time frame: Up to 32 days after CAS
Volume of new ischaemic brain lesions after CAS
Time frame: Up to 32 days after CAS
At least one new haemorrhagic brain lesion after CAS
Time frame: Up to 32 days after CAS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2022.
- Individual participant dataSharing planned: Yes. De-identified individual participant data will be available for further analyses. Specific requests will be considered by the Trial Steering Committee.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leo H Bonati, MD principal investigator
Department of Neurology and Stroke Center, University Hospital Basel
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ticagrelor, Clopidogrel and Aspirin in people with Carotid Artery Stenosis, run by University Hospital, Basel, Switzerland at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany, Switzerland, Belgium, Italy, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
At least one new ischaemic brain lesion after CAS (time frame: Up to 32 days after CAS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.