Revacept in Symptomatic Carotid Stenosis (Revacept/CS/02)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AdvanceCor GmbH
Sponsor:
Information provided by (Responsible Party):
AdvanceCor GmbH
ClinicalTrials.gov Identifier:
NCT01645306
First received: July 16, 2012
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks (TIAs), amaurosis fugax or stroke and presenting with microembolic signals (MES) receive either Revacept (single dose) plus antiplatelet monotherapy (Aspirin or Clopidogrel) or monotherapy alone with the aim of reducing MES.

Patients receive a single dose of trial medication by intravenous infusion for 20 minutes. The primary endpoint (MES 24 hours after treatment) is assessed. Patients are followed up one and three days after treatment, at 3 months and by a telephone interview at 12 months.


Condition Intervention Phase
Carotid Stenosis
Atherosclerosis
Stroke
Transient-ischaemic Attack
TIA
Amaurosis Fugax
Drug: Revacept
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AdvanceCor GmbH:

Primary Outcome Measures:
  • Change in incidence of microembolic signals (MES) [ Time Frame: 24 hours after treatment ] [ Designated as safety issue: No ]
    The primary efficacy objective is to evaluate whether the incidence of microembolic signals (MES) can be reduced in patients with symptomatic carotid artery stenosis who have been treated with Revacept plus antiplatelet monotherapy (aspirin or clopidogrel) versus antiplatelet monotherapy alone (placebo). MES will be assessed by transcranial Doppler (TCD) examination.


Secondary Outcome Measures:
  • Change in rate of MES per hour [ Time Frame: 24 hours after treatment ] [ Designated as safety issue: No ]
  • Assessment of neurological status (NIH Stroke Scale) [ Time Frame: 3 months after treatment ] [ Designated as safety issue: Yes ]
  • Cerebral lesion analysis by DWI-NMR and correlation to neurological status [ Time Frame: 1 day after CEA / intervention ] [ Designated as safety issue: Yes ]
  • Clinical endpoint rate of all cause death [ Time Frame: up to 12 months after treatment ] [ Designated as safety issue: Yes ]
  • Assessment of cardiovascular outcome [ Time Frame: 3 and 12 months ] [ Designated as safety issue: Yes ]
    myocardial infarction and re-intervention

  • Change in vital signs [ Time Frame: up to 3 months after treatment ] [ Designated as safety issue: Yes ]
  • Change in ECG parameters [ Time Frame: up to 3 months after treatment ] [ Designated as safety issue: Yes ]
  • Assessment of anti-drug antibody titres [ Time Frame: up to 3 months after treatment ] [ Designated as safety issue: Yes ]
  • Assessment of Adverse Events [ Time Frame: up to 3 months after treatment ] [ Designated as safety issue: Yes ]
    including wound healing complications, laboratory abnormalities and use of concomitant medication

  • Where feasible: Assessment of Haemostasis Safety [ Time Frame: up to 3 months after treatment ] [ Designated as safety issue: Yes ]
    laboratory parameters indicating thrombocytopenia and bleeding according to the RE-LY study group criteria, in vitro platelet function, in vitro bleeding time by PFA-100 / PFA-200

  • Clinical endpoint rate of stroke-related death [ Time Frame: up to 12 months after treatment ] [ Designated as safety issue: Yes ]
  • Clinical endpoint TIA, amaurosis fugax or stroke including haemorrhagic stroke [ Time Frame: up to 12 months after treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: March 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Phosphate buffered saline (PBS), 1% sucrose, 4% mannitol Drug: Placebo
single intravenous injection
Active Comparator: 40 mg Revacept
in phosphate buffered saline (PBS), 1% sucrose, 4% mannitol
Drug: Revacept
single intravenous injection
Active Comparator: 120 mg Revacept
in phosphate buffered saline (PBS), 1% sucrose, 4% mannitol
Drug: Revacept
single intravenous injection

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
      • MES detected by TCD (greater than or equal to 1 MES per hour)
      • Ipsilateral 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

    • Ipsilateral siphon or middle cerebral artery stenosis (tandem stenosis)
    • 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 other anti-platelet therapy than aspirin or clopidogrel within the last 3 weeks (3 days for dipyridamole extended release; 8 hours for tirofiban/Aggrastat)
    • Sustained hypertension (systolic BP > 179 mmHg or diastolic BP >109 mmHg), hypertensive patients shall be treated in accordance with current guidelines for the management of arterial hypertension
    • 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)
  4. Prohibited Treatments and/or therapies

    • Oral anticoagulation or dual antiplatelet therapy (aspirin combined with clopidogrel or other P2Y inhibitors) within the last 3 weeks; dipyridamole extended release within last 3 days; tirofiban/Aggrastat within the last 8 hours
    • Indication for oral anticoagulation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01645306

Contacts
Contact: Holger Poppert, PD Dr. med. 004989-4140 ext 4606

Locations
Germany
Site 01: Department of Neurology, TU Munich Recruiting
Munich, Bavaria, Germany
Contact: Holger Poppert, PD Dr. med.    004989-4140- ext 4606      
Contact: Angelika Henning         
Principal Investigator: Holger Poppert, PD Dr. med.         
Site 03: Universitätsklinikum Münster Recruiting
Münster, NRW, Germany, 48149
Contact: Ralf Dittrich, PD Dr. med.         
Contact: Dorothee Schulte to Bühne         
Principal Investigator: Ralf Dittrich, PD Dr. med.         
Principal Investigator: Rainer Dziewas, Prof. Dr. med.         
Site 10: Universitätsklinikum der Ruhr-Universität Bochum Recruiting
Bochum, Germany, 44791
Contact: Christos Krogias, Dr. med.    0234 / 509 ext 2410      
Principal Investigator: Christos Krogias, Dr. med.         
Principal Investigator: Saskia Meves, Dr. med.         
Site 08: Universitätsklinikum Essen, Klinik für Neurologie Recruiting
Essen, Germany, 45147
Contact: Vesna Zegarac, Dr. med.         
Contact: Melanie Dietzold         
Principal Investigator: Oliver Kastrup, Dr. med.         
Principal Investigator: Christian Weimar, Prof. Dr. med.         
Sub-Investigator: Vesna Zegarac, Dr. med.         
Site 07: Medizinische Hochschule Hannover, Klinik für Neurologie Recruiting
Hannover, Germany, 30625
Contact: Karin Weißenborn, Prof. Dr. med.         
Principal Investigator: Karin Weißenborn, Prof. Dr. med.         
Principal Investigator: Meike Heeren, Dr. med.         
Site 09: Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie Recruiting
Mainz, Germany
Contact: Christine Ziegelmayer    00496131 17 ext 2222      
Principal Investigator: Klaus Gröschel, PD Dr. med.         
Principal Investigator: Birklein Frank, Prof. Dr. med.         
Sub-Investigator: Tugba Ibis         
Sub-Investigator: Anne Grings         
Site 05: Klinik und Poliklinik für Neurologie der Universität Regensburg Recruiting
Regensburg, Germany, 93053
Contact: Felix Schlachetzki, Prof. Dr. med.         
Contact: Claudia Köppl         
Principal Investigator: Felix Schlachetzki, Prof. Dr. med.         
Principal Investigator: Sandra Boy, Dr. med.         
Site 04: Universitätsklinikum Tübingen, Klinik für Allgemeine Neurologie Recruiting
Tübingen, Germany, 72076
Contact: Sven Poli, Dr. med.    07071 29 ext 84427      
Contact: Julia Zeller         
Principal Investigator: Sven Poli, Dr. med.         
Principal Investigator: Ziemann Ulf, Prof. Dr. med.         
Site 06: Universitätsklinikum Ulm, Abteilung für Neurologie Recruiting
Ulm, Germany, 89081
Contact: Hermann Neugebauer, Dr. med.         
Contact: Sabine Raubold         
Principal Investigator: Hermann Neugebauer, Dr. med.         
Principal Investigator: Katharina Knauer, Dr. med.         
United Kingdom
25 - Addenbrookes Hospital Recruiting
Cambridge, United Kingdom, CB2 0QQ
Principal Investigator: Paul Hayes, MD         
23 - University Hospital Coventry NHS Trust Recruiting
Coventry, United Kingdom, CV2 2DX
Contact: Chris Imray, MD         
Principal Investigator: Chris Imray, MD         
Site 21: Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE2 7LX
Contact: Tom Robinson         
Principal Investigator: Tom Robinson         
Site 20: St George's NHS Trust Recruiting
London, United Kingdom, SW17 0QT
Principal Investigator: Ian M Loftus, MD         
28 - King's College London Hospital Recruiting
London, United Kingdom, SE5 8AF
Contact: Hisham Rashid         
Principal Investigator: Hisham Rashid         
26 - University College London Hospital Recruiting
London, United Kingdom, NW1 2BU
Contact: Toby Richards, MD         
Principal Investigator: Toby Richards, MD         
24 - University of Manchester Recruiting
Manchester, United Kingdom, M23 9LT
Contact: Charles McCollum, MD         
Principal Investigator: Charles McCollum, MD         
Sponsors and Collaborators
AdvanceCor GmbH
Investigators
Principal Investigator: Holger Poppert, PD Dr. med. Department of Neurology, TU Munich
Principal Investigator: Ian M Loftus, MD St George's NHS Trust
  More Information

Publications:

Responsible Party: AdvanceCor GmbH
ClinicalTrials.gov Identifier: NCT01645306     History of Changes
Other Study ID Numbers: Revacept/CS/02
Study First Received: July 16, 2012
Last Updated: July 31, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Blindness
Atherosclerosis
Arteriosclerosis
Carotid Stenosis
Ischemic Attack, Transient
Constriction, Pathologic
Stroke
Amaurosis Fugax
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Ischemia
Pathological Conditions, Anatomical
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Eye Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on August 28, 2014