Revacept in Symptomatic Carotid Stenosis

NCT ID: NCT01645306

Last Updated: 2021-01-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-08

Study Completion Date

2019-09-23

Brief Summary

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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

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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.

Conditions

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Carotid Stenosis Atherosclerosis Stroke Transient-ischaemic Attack TIA Amaurosis Fugax

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Phosphate buffered saline (PBS), 1% sucrose, 4% mannitol

Placebo control with PBS, 1% sucrose and 4% mannitol

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

single intravenous injection

40 mg Revacept

low dose Revacept 40mg in PBS, 1% sucrose, 4% mannitol

Group Type ACTIVE_COMPARATOR

Revacept

Intervention Type DRUG

single intravenous injection

120 mg Revacept

high dose revacept 120mg in PBS, 1% sucrose, 4% mannitol

Group Type ACTIVE_COMPARATOR

Revacept

Intervention Type DRUG

single intravenous injection

Interventions

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Revacept

single intravenous injection

Intervention Type DRUG

Placebo

single intravenous injection

Intervention Type DRUG

Other Intervention Names

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40 mg or 120 mg Control Group

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AdvanceCor GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Holger Poppert, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, TU Munich

Ian M Loftus, MD

Role: PRINCIPAL_INVESTIGATOR

St George's NHS Trust

Locations

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Site 01: Department of Neurology, TU Munich

Munich, Bavaria, Germany

Site Status

Site 08: Universitätsklinikum Essen, Klinik für Neurologie

Essen, , Germany

Site Status

Site 11: Universitätsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status

Site 07: Medizinische Hochschule Hannover, Klinik für Neurologie

Hanover, , Germany

Site Status

Site 12: Universitätsklinikum Leipzig AöR

Leipzig, , Germany

Site Status

Site 09: Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie

Mainz, , Germany

Site Status

Site 04: Universitätsklinikum Tübingen, Klinik für Allgemeine Neurologie

Tübingen, , Germany

Site Status

Site 06: Universitätsklinikum Ulm, Abteilung für Neurologie

Ulm, , Germany

Site Status

Site 23 - University Hospital Coventry NHS Trust

Coventry, , United Kingdom

Site Status

Site 26 - University College London Hospital

London, , United Kingdom

Site Status

Site 28 - King's College London Hospital

London, , United Kingdom

Site Status

Site 20: St George's NHS Trust

London, , United Kingdom

Site Status

Countries

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Germany United Kingdom

References

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Bultmann A, Li Z, Wagner S, Peluso M, Schonberger T, Weis C, Konrad I, Stellos K, Massberg S, Nieswandt B, Gawaz M, Ungerer M, Munch G. Impact of glycoprotein VI and platelet adhesion on atherosclerosis--a possible role of fibronectin. J Mol Cell Cardiol. 2010 Sep;49(3):532-42. doi: 10.1016/j.yjmcc.2010.04.009. Epub 2010 Apr 27.

Reference Type BACKGROUND
PMID: 20430036 (View on PubMed)

Goertler M, Baeumer M, Kross R, Blaser T, Lutze G, Jost S, Wallesch CW. Rapid decline of cerebral microemboli of arterial origin after intravenous acetylsalicylic acid. Stroke. 1999 Jan;30(1):66-9. doi: 10.1161/01.str.30.1.66.

Reference Type BACKGROUND
PMID: 9880390 (View on PubMed)

Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation. 2005 May 3;111(17):2233-40. doi: 10.1161/01.CIR.0000163561.90680.1C. Epub 2005 Apr 25.

Reference Type BACKGROUND
PMID: 15851601 (View on PubMed)

Massberg S, Konrad I, Bultmann A, Schulz C, Munch G, Peluso M, Lorenz M, Schneider S, Besta F, Muller I, Hu B, Langer H, Kremmer E, Rudelius M, Heinzmann U, Ungerer M, Gawaz M. Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo. FASEB J. 2004 Feb;18(2):397-9. doi: 10.1096/fj.03-0464fje. Epub 2003 Dec 4.

Reference Type BACKGROUND
PMID: 14656994 (View on PubMed)

Molloy J, Markus HS. Asymptomatic embolization predicts stroke and TIA risk in patients with carotid artery stenosis. Stroke. 1999 Jul;30(7):1440-3. doi: 10.1161/01.str.30.7.1440.

Reference Type BACKGROUND
PMID: 10390320 (View on PubMed)

Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor? Blood. 2003 Jul 15;102(2):449-61. doi: 10.1182/blood-2002-12-3882. Epub 2003 Mar 20.

Reference Type BACKGROUND
PMID: 12649139 (View on PubMed)

Ringelstein EB, Droste DW, Babikian VL, Evans DH, Grosset DG, Kaps M, Markus HS, Russell D, Siebler M. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke. 1998 Mar;29(3):725-9. doi: 10.1161/01.str.29.3.725.

Reference Type BACKGROUND
PMID: 9506619 (View on PubMed)

Schonberger T, Siegel-Axel D, Bussl R, Richter S, Judenhofer MS, Haubner R, Reischl G, Klingel K, Munch G, Seizer P, Pichler BJ, Gawaz M. The immunoadhesin glycoprotein VI-Fc regulates arterial remodelling after mechanical injury in ApoE-/- mice. Cardiovasc Res. 2008 Oct 1;80(1):131-7. doi: 10.1093/cvr/cvn169. Epub 2008 Jun 19.

Reference Type BACKGROUND
PMID: 18566102 (View on PubMed)

Ungerer M, Rosport K, Bultmann A, Piechatzek R, Uhland K, Schlieper P, Gawaz M, Munch G. Novel antiplatelet drug revacept (Dimeric Glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation. 2011 May 3;123(17):1891-9. doi: 10.1161/CIRCULATIONAHA.110.980623. Epub 2011 Apr 18.

Reference Type BACKGROUND
PMID: 21502572 (View on PubMed)

Jamasbi J, Megens RT, Bianchini M, Munch G, Ungerer M, Faussner A, Sherman S, Walker A, Goyal P, Jung S, Brandl R, Weber C, Lorenz R, Farndale R, Elia N, Siess W. Differential Inhibition of Human Atherosclerotic Plaque-Induced Platelet Activation by Dimeric GPVI-Fc and Anti-GPVI Antibodies: Functional and Imaging Studies. J Am Coll Cardiol. 2015 Jun 9;65(22):2404-15. doi: 10.1016/j.jacc.2015.03.573.

Reference Type BACKGROUND
PMID: 26046734 (View on PubMed)

Kleiman NS, Kolandaivelu K. Expanding the Roster: Developing New Inhibitors of Intravascular Thrombosis. J Am Coll Cardiol. 2015 Jun 9;65(22):2416-9. doi: 10.1016/j.jacc.2015.03.576. No abstract available.

Reference Type BACKGROUND
PMID: 26046735 (View on PubMed)

Uphaus T, Richards T, Weimar C, Neugebauer H, Poli S, Weissenborn K, Imray C, Michalski D, Rashid H, Loftus I, Rummey C, Ritter M, Hauser TK, Munch G, Groschel K, Poppert H. Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Multicenter Randomized Phase II Trial. Stroke. 2022 Sep;53(9):2718-2729. doi: 10.1161/STROKEAHA.121.037006. Epub 2022 Jun 13.

Reference Type DERIVED
PMID: 35695006 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Revacept/CS/02

Identifier Type: -

Identifier Source: org_study_id

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