Platelet Inhibition and Transcranial Doppler (TCD)-Detected Microemboli During and After Carotid Artery Stenting (CAS) in Asymptomatic Patients Prior to Cardiac Surgery

NCT01146301 | Completed Phase 4 DMC

• 1 other identifier: R-06.44A
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Carotid Stenosis

Keywords

Platelet Aggregation Inhibitors; Coronary Artery Bypass Grafting

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

300 mg Loading dose clopidogrel

ACTIVE COMPARATOR

Drug: Clopidogrel

600 mg Loading dose of clopidogrel

EXPERIMENTAL

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

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

300 mg Loading dose clopidogrel; 600 mg Loading dose of clopidogrel

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patient \> 18 years of age
• patient accepted for CAS
• temporal window for TCD available

You may not qualify if:

• 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
• patients with active bleeding or at high-risk of bleeding
• uncontrolled hypertension ( \> 180/110 mmHg) despite optimal medication
• pregnancy and women with inadequate anticonception

Sponsors & Collaborators

• R&D Cardiologie: lead

Study Sites (1)

St-Antonius Ziekenhuis

Nieuwegein, Utrecht, 3435CM, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 23138609 DERIVED

MeSH Terms

Conditions

Carotid Stenosis

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 14, 2010
• First Posted: June 17, 2010
• Study Start: March 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: April 1, 2010
• Last Updated: June 22, 2010

Record last verified: 2010-06

Locations

NL (1)