Clinical trial NCT01645306: Revacept in Symptomatic Carotid Stenosis
Official title: Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Phase II, Multicentre; Randomised, Dose-finding, Double-blind and Placebo Controlled Superiority Study With Parallel Groups
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carotid Stenosis
Atherosclerosis
Stroke
Transient-ischaemic Attack
TIA
Amaurosis Fugax
Lead sponsor: AdvanceCor GmbH
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks (TIAs), amaurosis fugax or stroke receive either Revacept (single dose) plus antiplatelet monotherapy or monotherapy alone.

Patients receive a single dose of trial medication by intravenous infusion for 20 minutes. Patients are followed up one and three days after treatment, at 3 months and by a telephone interview at 12 months.

Detailed description: Patients had a more than 50% carotid artery stenosis according to ECST and suffered from ischemic stroke, transitory ischemic attack or intermittent blindness (amaurosis fugax) within the last 30 days. All patients were on standard medication with aspirin or clopidogrel and received heparin for thrombosis prophylaxis. Carotid endarterectomy (CEA), carotid stenting (CAS) or best medical therapy for treatment of the carotid stenosis and prevention of secondary thrombo-emboli was performed according to guidelines. Additional treatment with Revacept or placebo was done on top of the standard therapy. Therefore the control group receiving placebo was already on the standard medical therapy for patients with symptomatic carotid stenosis and received also the guideline conform interventions CEA, CAS or best medical therapy.

Secondary prophylaxis of thrombo-embolic ischemic events by Revacept should be investigated. Therefore microemboli were detected by transcranial Doppler and ischemic brain lesions were investigated by diffusion weighted imaging magnetic resonance imaging (DWI-MRI) scan as exploratory endpoints. Moreover clinical endpoints such as stroke, TIA, myocardial infarction, coronary intervention and death were investigated at 1 week, 3 months and 12 months follow-up. Safety was closely monitored with emphasis on bleeding complications as bleeding is the most dreaded complication of anti-thrombotic agents especially in patients with cerebral strokes.

Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent
2. Target population

   * Diagnosis:

     * Extracranial carotid artery stenosis (diagnosed by vascular duplex ultrasound peak flow or angiography)
     * Lesions with ≥ 50 % stenosis according to the European Carotid Surgery Trial (ECST) criteria
     * TIA, amaurosis fugax or stroke within the last 30 days
   * Age and sex: Men and women aged \> 18 years Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after receiving investigational product in such a manner that the risk of pregnancy is minimised.

Exclusion Criteria:

1. Sex and reproductive Status:

   * WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 4 weeks after receiving investigational product.
   * Women who are pregnant or breastfeeding
   * Women with a positive pregnancy test on enrollment or prior to investigational product administration.
2. Target disease exceptions

   * NIHSS score \> 18
   * Recent intracerebral haemorrhage by X-ray computed tomography (CT) or nuclear magnetic resonance (NMR)
   * Cardiac cause of embolisation (atrial fibrillation or other cardiac source e.g. artificial heart valves)
3. Medical history and concurrent disease

   * History of hypersensitivity, contraindication or serious adverse reaction to inhibitors of platelet aggregation, hypersensitivity to related drugs (cross-allergy) or to any of the excipients in the study drug
   * History or evidence of thrombocytopenia (\<30.000/ul), bleeding diathesis or coagulopathy (pathological international normalised ratio (INR) or activated partial thromboplastin time (aPTT))
   * Thrombolysis within the last 48 hours
   * Relevant haemorrhagic transformation as determined by CT, NMR or anamnesis
   * Oral anticoagulation or dual anti-platelet therapy with aspirin or clopidogrel and other P2Y inhibitors at screening (3 days for dipyridamole extended release; 8 hours for tirofiban/Aggrastat)
   * Sustained hypertension (systolic BP \> 179 mmHg or diastolic BP \>109 mmHg)
   * History of severe systemic disease such as terminal carcinoma, renal failure (or current creatinine \> 200 umol/l), cirrhosis, severe dementia, or psychosis
   * Current severe liver dysfunction (transaminase level greater than 5-fold over upper normal range limit)
   * Active autoimmune disorder such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis or glomerulonephritis
   * Known atrial fibrillation or other clinically significant ECG abnormalities (at present)

Primary outcomes:
measure: New DWI Lesion(s)
timeFrame: 1 day post intervention
Secondary outcomes:
Other outcomes:
measure: Patients With Any Stroke or Transient Ischemic Attack (TIA)
timeFrame: 90 days after IMP application
measure: Major Bleedings
timeFrame: 90 days after IMP application
measure: Any Clinical Event
timeFrame: 365 days after IMP application
measure: Anti-Drug Antibodies
timeFrame: 3 month (+/- 1 month) after IMP application
measure: Participants With Adverse Events (AEs)
timeFrame: ~ 365 days after IMP application (whole study period)
Locations:
city: Munich
country: Germany
facility: Site 01: Department of Neurology, TU Munich
state: Bavaria
city: Essen
country: Germany
facility: Site 08: Universitätsklinikum Essen, Klinik für Neurologie
city: Hamburg
country: Germany
facility: Site 11: Universitätsklinikum Hamburg Eppendorf
city: Hannover
country: Germany
facility: Site 07: Medizinische Hochschule Hannover, Klinik für Neurologie
city: Leipzig
country: Germany
facility: Site 12: Universitätsklinikum Leipzig AöR
city: Mainz
country: Germany
facility: Site 09: Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie
city: Tübingen
country: Germany
facility: Site 04: Universitätsklinikum Tübingen, Klinik für Allgemeine Neurologie
city: Ulm
country: Germany
facility: Site 06: Universitätsklinikum Ulm, Abteilung für Neurologie
city: Coventry
country: United Kingdom
facility: Site 23 - University Hospital Coventry NHS Trust
city: London
country: United Kingdom
facility: Site 26 - University College London Hospital
city: London
country: United Kingdom
facility: Site 28 - King's College London Hospital
city: London
country: United Kingdom
facility: Site 20: St George's NHS Trust
Study officials:
affiliation: Department of Neurology, TU Munich
name: Holger Poppert, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: St George's NHS Trust
name: Ian M Loftus, MD
role: PRINCIPAL_INVESTIGATOR
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