Carotid StenosisPhase 4IMPACTNCT01146301
Platelet Inhibition and Transcranial Doppler (TCD)-Detected Microemboli During and After Carotid Artery Stenting (CAS) in Asymptomatic Patients Prior to Cardiac Surgery
A Phase 4 study testing Clopidogrel in people with Carotid Stenosis, run by R&D Cardiologie at 1 site in Netherlands.
Trial summary
As with coronary artery stenting, activation and embolisation of platelets occurs with carotid artery stenting (CAS). Based on promising data on the use of clopidogrel plus aspirin in coronary stenting this dual antiplatelet regimen has been introduced as adjunctive treatment during CAS. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Carotid Stenosis
- What is being tested?
- Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- Not given
- Where
- 1 siteNetherlands
- Study dates
- Mar 2008to Apr 2010
- Phase
- Phase 4
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patient > 18 years of age
- patient accepted for CAS
- temporal window for TCD available
Who cannot join
- severe renal impairment (creatinine> 1.5mg/dl), abnormal liver function, malignancy, febrile disorder, acute or chronic inflammatory disease and other diseases influencing platelet reactivity
- extreme tortuositas or calcification of the lesion
- inadequate arterial access
- contraindication for angiography
- patient already receiving clopidogrel
- contra-indication to study drugs
Show all 9Show fewer
- patients with active bleeding or at high-risk of bleeding
- uncontrolled hypertension ( > 180/110 mmHg) despite optimal medication
- pregnancy and women with inadequate anticonception
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does the Magnitude of Platelet Inhibition Inversely Correlate With the Number of TCD-detected Microemboli in Asymptomatic Patients Undergoing Carotid Artery Stenting Prior to Cardiac Surgery Who Are Being Pre-treated With 300 mg or 600 mg Loading Dose of Clopidogrel?
As with coronary artery stenting, activation and embolisation of platelets occurs with carotid artery stenting (CAS). Based on promising data on the use of clopidogrel plus aspirin in coronary stenting this dual antiplatelet regimen has been introduced as adjunctive treatment during CAS. There is as yet, however, no randomized controlled trial which compared different loading doses of clopidogrel during CAS. Taking into account that a wide interindividual variability in the response to a loading of clopidogrel exists, this study is intended to establish the optimal loading dose of clopidogrel. Therefore platelet function testing and a 1-hour of postprocedural TCD (transcranial doppler) monitoring will be performed.
Objective: Firstly, to investigate whether the absolute magnitude of Platelet Inhibition inversely correlates with the number of TCD-detected microemboli during and after CAS in patients who are being pre-treated with either a 300 mg or a 600 mg loading dose of clopidogrel. Secondly, if there is any impact on early neurological outcome determined by the loading dose of clopidogrel.
Read the detailed description
Carotid angioplasty with stent placement (CAS) has become a well-accepted treatment option for carotid artery stenosis. In combination with experience in CAS procedures and the introduction of protection devices and low-profile systems, the periprocedural risk of thromboembolic complications are comparable to that of standard surgical carotid endarterectomy (CEA) In our centre, all patients with severe asymptomatic carotid artery disease ( luminal diameter reduction of more than 80%, according to NASCET criteria) scheduled for cardiac surgery are eligible for CAS.
As with coronary artery stenting , activation and embolisation of platelets occurs with CAS. Based on promising data on the use of clopidogrel plus aspirin in coronary stenting, this dual antiplatelet regimen has been introduced in CAS. Specifically, an antiplatelet regimen with aspirin(300mg) and a 300 mg loading dose of clopidogrel at least 24 hours before carotid angioplasty has currently been the treatment of choice in carotid angioplasty with stent placement.
However, several studies have reported a wide interindividual variability in the response to a 300 mg loading of clopidogrel with a subsequent substantial proportion of patients not receiving the optimal benefit from it. Therefore, it has been suggested that a 600 mg loading dose will result in a faster onset, a higher responsiveness and a higher magnitude of platelet inhibition without any increase in bleeding complications. For these reasons, the interventional cardiology has already adopted the 600 mg loading dose regimen as standard of care during percutaneous coronary interventions. There is as yet, however, no randomized controlled trial which compared different loading doses of clopidogrel during CAS.
Using transcranial Doppler (TCD) monitoring of the middle cerebral artery during CAS, it is possible to register the number of TCD-detected microembolic signals during and after CAS. This monitoring enables the operator to diminish the risk of stroke during CAS. However, a significant number of patients develop an ischemic stroke in the hours following CAS after a symptom-free interval As published by van der Schaaf et al., in TCD monitoring after CEA, one hour of monitoring appeared to be effective to select those patients in whom the number of microemboli did not spontaneously decrease. More important, postoperative TCD monitoring was able to detect those patients who were at risk for new adverse cerebral events after the operation. Other studies demonstrate the potential application of ultrasonic emboli detection to examine the efficacy of new platelet agents in relatively small number of patients.
It remains to be established whether a higher magnitude of platelet inhibition before CAS has an additional protective effect by decreasing the microembolic load measured on TCD after the procedure. Moreover, such a TCD-monitoring post-CAS has not been performed systematically in the past and thus could reveal valuable information helpful to the understanding of post procedural cerebral complications and risk stratification.
- Conditions
- Carotid Stenosis
- Being tested
- Clopidogrel
- Keywords
- Platelet Aggregation Inhibitors, Coronary Artery Bypass Grafting
- Medical subject headings
- Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
All patients will receive a loading dose of 600mg of study medication. The first group will receive 300 mg of clopidogrel and 300 mg placebo, the second group will receive 600mg of clopidogrel at least 24h before carotid stenting
| Study group | Role | What they receive |
|---|---|---|
| 300 mg Loading dose clopidogrel | Active comparator | Not described Receives: Drug: Clopidogrel |
| 600 mg Loading dose of clopidogrel | Experimental | Not described Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of TCD-detected microemboli during and immediately after the CAS procedure.
The TCD monitoring of the Middle cerebral artery will be started during and immediately after the CAS procedure , using a 2 MHz TCD ultrasound probe. The Doppler spectra will be observed on-line and the audio-Doppler signal will be made audible in the angiography suite. For off-line analysis, the audio Doppler signals will be recorded on CD ROM. Analysis of recordings will be performed by an observer blinded to the clinical details and study group. Standard criteria for microemboli detection will be used.
The absolute level of platelet inhibition
Blood samples for platelet function testing will be drawn at two different time-points: Before the administration of the study medication (baseline value) and immediately before the CAS-procedure. (time-interval will be approximately 24 hours) Platelet function testing will be performed with several platelet function assays: "classical"light transmittance aggregometry, The VerifyNow P2Y12 assay, Thrombelastograph® (TEG®) PlaletetMapping™ Assay and the Platelet function analyser (PFA-100).
Secondary outcomes (1)
Periprocedural adverse cerebral events
All patients will be assessed prior to treatment, at discharge and at 30 days following the procedure by an independent stroke neurologist. Strokes will be considered disabling (major), if patients has a modified Rankin score of more than 3, at 30 days after onset of symptoms. A minor stroke is defined as a Rankin score of 3 or less that resolves completely within 30 days. Transient ischemic attack and amaurosis fugax are diagnosed if the symptoms disappear within 24 hours. Fatal stroke is defined as death attributed to an ischemic or hemorrhagic stroke.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2010 (estimated)
- Study startMar 2008
- Primary completionMar 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carotid StenosisStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
Sponsor and investigators
- Lead sponsor
- R&D Cardiologie
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01146301
- Sponsor's protocol ID
- R-06.44A
- Acronym
- IMPACT
- Status last verified
- Jun 2010
- First submitted
- 14 Jun 2010
- Last updated
- 22 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Van Der Heyden J, Van Werkum J, Hackeng CM, Kelder JC, Breet NJ, Deneer VH, Ackerstaff RG, Tromp SC, De Vries JP, Vos JA, Suttorp MJ, Elsenberg EH, Van Neerven D, Schonewille WJ, Wolters F, Ten Berg JM. High versus standard clopidogrel loading in patients undergoing carotid artery stenting prior to cardiac surgery to assess the number of microemboli detected with transcranial Doppler: results of the randomized IMPACT trial. J Cardiovasc Surg (Torino). 2013 Jun;54(3):337-47. Epub 2012 Nov 8.
PubMed 23138609
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does the Magnitude of Platelet Inhibition Inversely Correlate With the Number of TCD-detected Microemboli in Asymptomatic Patients Undergoing Carotid Artery Stenting Prior to Cardiac Surgery Who Are Being Pre-treated With 300 mg or 600 mg Loading Dose of Clopidogrel?
- ClinicalTrials.gov ID
- NCT01146301
- Acronym / sponsor ID
- IMPACT / R-06.44A
- Conditions
- Carotid Stenosis
- Keywords
- Platelet Aggregation Inhibitors, Coronary Artery Bypass Grafting
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- R&D CardiologieUniversity, hospital or other
- Study start
- Mar 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 17 Jun 2010 (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.
As with coronary artery stenting, activation and embolisation of platelets occurs with carotid artery stenting (CAS). Based on promising data on the use of clopidogrel plus aspirin in coronary stenting this dual antiplatelet regimen has been introduced as adjunctive treatment during CAS. There is as yet, however, no randomized controlled trial which compared different loading doses of clopidogrel during CAS. Taking into account that a wide interindividual variability in the response to a loading of clopidogrel exists, this study is intended to establish the optimal loading dose of clopidogrel. Therefore platelet function testing and a 1-hour of postprocedural TCD (transcranial doppler) monitoring will be performed.
Objective: Firstly, to investigate whether the absolute magnitude of Platelet Inhibition inversely correlates with the number of TCD-detected microemboli during and after CAS in patients who are being pre-treated with either a 300 mg or a 600 mg loading dose of clopidogrel. Secondly, if there is any impact on early neurological outcome determined by the loading dose of clopidogrel.
Detailed description
Carotid angioplasty with stent placement (CAS) has become a well-accepted treatment option for carotid artery stenosis. In combination with experience in CAS procedures and the introduction of protection devices and low-profile systems, the periprocedural risk of thromboembolic complications are comparable to that of standard surgical carotid endarterectomy (CEA) In our centre, all patients with severe asymptomatic carotid artery disease ( luminal diameter reduction of more than 80%, according to NASCET criteria) scheduled for cardiac surgery are eligible for CAS.
As with coronary artery stenting , activation and embolisation of platelets occurs with CAS. Based on promising data on the use of clopidogrel plus aspirin in coronary stenting, this dual antiplatelet regimen has been introduced in CAS. Specifically, an antiplatelet regimen with aspirin(300mg) and a 300 mg loading dose of clopidogrel at least 24 hours before carotid angioplasty has currently been the treatment of choice in carotid angioplasty with stent placement.
However, several studies have reported a wide interindividual variability in the response to a 300 mg loading of clopidogrel with a subsequent substantial proportion of patients not receiving the optimal benefit from it. Therefore, it has been suggested that a 600 mg loading dose will result in a faster onset, a higher responsiveness and a higher magnitude of platelet inhibition without any increase in bleeding complications. For these reasons, the interventional cardiology has already adopted the 600 mg loading dose regimen as standard of care during percutaneous coronary interventions. There is as yet, however, no randomized controlled trial which compared different loading doses of clopidogrel during CAS.
Using transcranial Doppler (TCD) monitoring of the middle cerebral artery during CAS, it is possible to register the number of TCD-detected microembolic signals during and after CAS. This monitoring enables the operator to diminish the risk of stroke during CAS. However, a significant number of patients develop an ischemic stroke in the hours following CAS after a symptom-free interval As published by van der Schaaf et al., in TCD monitoring after CEA, one hour of monitoring appeared to be effective to select those patients in whom the number of microemboli did not spontaneously decrease. More important, postoperative TCD monitoring was able to detect those patients who were at risk for new adverse cerebral events after the operation. Other studies demonstrate the potential application of ultrasonic emboli detection to examine the efficacy of new platelet agents in relatively small number of patients.
It remains to be established whether a higher magnitude of platelet inhibition before CAS has an additional protective effect by decreasing the microembolic load measured on TCD after the procedure. Moreover, such a TCD-monitoring post-CAS has not been performed systematically in the past and thus could reveal valuable information helpful to the understanding of post procedural cerebral complications and risk stratification.
Study design
- Primary purpose
- Treatment
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 300 mg Loading dose clopidogrel | Active comparator | Drug: Clopidogrel |
| 600 mg Loading dose of clopidogrel | Experimental | Drug: Clopidogrel |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- patient > 18 years of age
- patient accepted for CAS
- temporal window for TCD available
Key exclusion criteria (9 listed)
- severe renal impairment (creatinine> 1.5mg/dl), abnormal liver function, malignancy, febrile disorder, acute or chronic inflammatory disease and other diseases influencing platelet reactivity
- extreme tortuositas or calcification of the lesion
- inadequate arterial access
- contraindication for angiography
- patient already receiving clopidogrel
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 |
|---|---|---|
| ClopidogrelAll patients will receive a loading dose of 600mg of study medication. The first group will receive 300 mg of clopidogrel and 300 mg placebo, the second group will receive 600mg of clopidogrel at least 24h before carotid stenting | Drug | 300 mg Loading dose clopidogrel, 600 mg Loading dose of clopidogrel |
Primary outcome
The number of TCD-detected microemboli during and immediately after the CAS procedure.
The TCD monitoring of the Middle cerebral artery will be started during and immediately after the CAS procedure , using a 2 MHz TCD ultrasound probe. The Doppler spectra will be observed on-line and the audio-Doppler signal will be made audible in the angiography suite. For off-line analysis, the audio Doppler signals will be recorded on CD ROM. Analysis of recordings will be performed by an observer blinded to the clinical details and study group. Standard criteria for microemboli detection will be used.
The absolute level of platelet inhibition
Blood samples for platelet function testing will be drawn at two different time-points: Before the administration of the study medication (baseline value) and immediately before the CAS-procedure. (time-interval will be approximately 24 hours) Platelet function testing will be performed with several platelet function assays: "classical"light transmittance aggregometry, The VerifyNow P2Y12 assay, Thrombelastograph® (TEG®) PlaletetMapping™ Assay and the Platelet function analyser (PFA-100).
1 secondary outcome
Periprocedural adverse cerebral events
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 22 Jun 2010.
- Derived from this study: PubMed 23138609Van Der Heyden J, Van Werkum J, Hackeng CM, Kelder JC, Breet NJ, Deneer VH, Ackerstaff RG, Tromp SC, De Vries JP, Vos JA, Suttorp MJ, Elsenberg EH, Van Neerven D, Schonewille WJ, Wolters F, Ten Berg JM. High versus standard clopidogrel loading in patients undergoing carotid artery stenting prior to cardiac surgery to assess the number of microemboli detected with transcranial Doppler: results of the randomized IMPACT trial. J Cardiovasc Surg (Torino). 2013 Jun;54(3):337-47. Epub 2012 Nov 8.
Related trials for Carotid Stenosis
Active, not recruitingObservational study
Symptomatic Carotid Outcomes Registry
Carotid Stenosis, Ischemic Stroke
Not yet recruitingObservational study
PET-MR Imaging of Natriuretic Peptide Receptor C (NPR-C) in Carotid Atherosclerosis With 64Cu-NODAGA-CANF (Multisite)
Carotid Atherosclerosis, Carotid Artery Stenosis Asymptomatic
Not yet recruitingObservational study
A Prospective, Multicenter, Single Arm Registry of ENROUTE NPS in Conjunction With Carotid WALLSTENT in Chinese Population
Carotid Artery Stenosis
Not yet recruitingObservational study
Vascular Health and Function in Cystic Fibrosis
Cystic Fibrosis, Endothelial Dysfunction
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clopidogrel in people with Carotid Stenosis, run by R&D Cardiologie at 1 site in Netherlands.
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 3 inclusion and 9 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 22 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
The number of TCD-detected microemboli during and immediately after the CAS procedure.. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01146301, which also lists 1 linked publication.
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 22 Jun 2010.