Clinical trial NCT03312855: Intracoronary Stenting and Antithrombotic Regimen: Lesion Platelet Adhesion as Selective Target of Endovenous Revacept
Official title: Revacept, a Novel Inhibitor of Platelet Adhesion in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Interventions: a Phase II, Multicentre, Randomised, Double-blind and Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stable Coronary Artery Disease
Keywords: coronary artery disease
platelet inhibition
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: AdvanceCor GmbH
name: Technical University of Munich
name: German Federal Ministry of Education and Research
First posted: 2017-10-18
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: with 2 doses (80 and 160 mg) of Revacept versus placebo
Primary purpose: TREATMENT

Brief summary: The main objective is to evaluate the efficacy and safety of treatment with 2 doses (80 and 160 mg) of Revacept versus placebo in patients with stable coronary artery disease undergoing PCI.

Detailed description: Revacept is a protein that is made up of an Fc fragment ("fragment crystallisable") fused to the GPVI receptor (the endogenous platelet collagen receptor). Consequently, Revacept binds to its ligand (collagen) on atherosclerotic plaques preventing circulating thrombocytes from binding to collagen exposed by the injured plaque. All this is achieved without affecting systemic hemostasis.

Thus, blocking of GPVI-dependent pathways by interfering with vascular collagen sites is commonly seen as an attractive target for an anti-platelet therapy of atherosclerotic diseases.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* Men and women \>18 years of age
* Diagnosis: Clinically stable coronary artery disease
* Angiographic evidence of coronary artery disease
* Indication for PCI

Exclusion Criteria:

* 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 or are planning pregnancy during course of trial
* Women with a positive pregnancy test on enrolment or prior to investigational product administration.
* Patients with elevated high sensitivity cardiac troponin T levels at screening
* Patients receiving antithrombotic therapy with Prasugrel or Ticagrelor within 7 days prior to randomisation
* History of hypersensitivity, contraindication or serious adverse reaction to any component of the study drug (GPVI-Fc, sucrose, mannitol), acetylsalicylic acid or clopidogrel
* History of bleeding diathesis or active bleeding within the last 30 days
* Recent intracerebral haemorrhage or trauma within the last 3 months
* Thrombocytopenia (platelet count \<30000/mm3) at screening
* Sustained hypertension (systolic BP \>179mmHg or diastolic BP \>109mmHg) at screening
* Renal failure (estimated glomerular filtration rate \< 30ml/min and/or dialysis)
* Severe systemic disease, such as known malignancies or other comorbid conditions with life expectancy less than one year that may result in protocol non-compliance
* Unable to provide informed consent (e.g. severe dementia, or psychosis)
* Current severe liver dysfunction (transaminase level \>5-fold the upper normal range limit)
* Patients with an indication for anticoagulant therapy
* Participation in any other clinical interventional trial (drug/device) within less than 30 days prior to screening
* Any other contraindication to perform PCI
* Any planned additional PCI or surgery within 30 days after randomization
* Suspected poor capability to follow instructions and cooperate
* Prisoners or subjects who are involuntarily incarcerated
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness (e.g. infectious disease)

Primary outcomes:
measure: Primary endpoint-composite endpoint of death and myocardial injury
timeFrame: within 48 hours from randomisation
Secondary outcomes:
measure: All cause mortality
timeFrame: within 30 days after randomisation
measure: Myocardial infarction
timeFrame: within 30 days after randomisation
measure: PCI-related (type 4) myocardial infarction
timeFrame: within 30 days after randomisation
measure: Definite stent thrombosis
timeFrame: within 30 days after randomisation
measure: Urgent coronary revascularization
timeFrame: within 30 days after randomisation
measure: Stroke
timeFrame: within 30 days after randomisation
measure: Peak potprocedural high-sensitivity troponin T level
timeFrame: within 48 hours after randomisation
measure: Bleeding class 2 or higher according to Bleeding Academic Research Consortium (BARC) criteria (safety endpoint)
timeFrame: within 30 days after randomisation
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Deutsches Herzzentrum München
state: Bavaria
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin, Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Virchow
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt, Medizinische Klinik III, Kardiologie
city: Mainz
country: Germany
facility: Universtätsmedizin Mainz, Zentrum für Kardiologie/Kardiologie I
city: Munich
country: Germany
facility: Klinikum der Universität München, Medizinische Klinik und Poliklinik I
city: Munich
country: Germany
facility: Klinikum rechts der Isar, I. Medizinische Klinik und Poliklinik
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
Study officials:
affiliation: Deutsches Herzzentrum München
name: Adnan Kastrati, MD
role: STUDY_CHAIR
affiliation: Klinikum der Universität München
name: Steffen Massberg, MD
role: STUDY_CHAIR
affiliation: Deutsches Herzzentrum Muenchen
name: Stefanie Schuepke, MD
role: STUDY_DIRECTOR
References:
citation: Mayer K, Hein-Rothweiler R, Schupke S, Janisch M, Bernlochner I, Ndrepepa G, Sibbing D, Gori T, Borst O, Holdenrieder S, Kupka D, Petzold T, Bradaric C, Okrojek R, Leistner DM, Trippel TD, Munzel T, Landmesser U, Pieske B, Zeiher AM, Gawaz MP, Hapfelmeier A, Laugwitz KL, Schunkert H, Kastrati A, Massberg S. Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial. JAMA Cardiol. 2021 Jul 1;6(7):753-761. doi: 10.1001/jamacardio.2021.0475.