Revacept in Symptomatic Carotid Stenosis

Phase 2

Completed

• Conditions: TIA; Stroke; Amaurosis Fugax; Carotid Stenosis; Atherosclerosis; Transient-ischaemic Attack
• Interventions: Drug: Placebo; Drug: Revacept

• Registration Number: NCT01645306
• Lead Sponsor: AdvanceCor GmbH

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.

Study Timeline

• Study First Submitted: 2012-07-16
• Study First Submitted QC: 2012-07-19
• Study First Posted: 2012-07-20
• Study Start: 2013-03-08
• Primary Completion: 2018-10-05
• Study Completion: 2019-09-23
• Results First Submitted: 2020-11-12
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-27
• Last Update Submitted: 2021-01-27
• Results First Posted: 2021-01-28
• Last Update Posted: 2021-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 158

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.

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phosphate buffered saline (PBS), 1% sucrose, 4% mannitol	Placebo	Placebo control with PBS, 1% sucrose and 4% mannitol
40 mg Revacept	Revacept	low dose Revacept 40mg in PBS, 1% sucrose, 4% mannitol
120 mg Revacept	Revacept	high dose revacept 120mg in PBS, 1% sucrose, 4% mannitol

Primary Outcome Measures

Name	Time	Method
New DWI Lesion(s)	1 day post intervention	The number of new diffusion weighted imaging (DWI) lesion(s) reported. (1 day after intervention compared to baseline).

Trial Locations

Locations (12)

Site 08: Universitätsklinikum Essen, Klinik für Neurologie; 🇩🇪 Essen, Germany

Site 11: Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

Site 12: Universitätsklinikum Leipzig AöR; 🇩🇪 Leipzig, Germany

Site 07: Medizinische Hochschule Hannover, Klinik für Neurologie; 🇩🇪 Hannover, Germany

Site 09: Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie; 🇩🇪 Mainz, Germany

Site 04: Universitätsklinikum Tübingen, Klinik für Allgemeine Neurologie; 🇩🇪 Tübingen, Germany

Site 06: Universitätsklinikum Ulm, Abteilung für Neurologie; 🇩🇪 Ulm, Germany

Site 26 - University College London Hospital; 🇬🇧 London, United Kingdom

Site 20: St George's NHS Trust; 🇬🇧 London, United Kingdom

Site 23 - University Hospital Coventry NHS Trust; 🇬🇧 Coventry, United Kingdom

Site 01: Department of Neurology, TU Munich; 🇩🇪 Munich, Bavaria, Germany

Site 28 - King's College London Hospital; 🇬🇧 London, United Kingdom