Bentracimab (PB2452) in Ticagrelor-treated Patients With Uncontrolled Major or Life-Threatening Bleeding or Requiring Urgent Surgery or Invasive Procedure (REVERSE-IT)
Hemorrhage, Urgent Surgery, Invasive Procedure
About this trial
This is an interventional treatment trial for Hemorrhage focused on measuring Bleeding
Eligibility Criteria
Inclusion Criteria:
Patients will be eligible for inclusion into the study if they meet all of the following criteria:
- Male or female >18 years of age with documented or verbal informed consent. Emergency consent may be obtained where permitted by local regulations and institutional approval.
- History or documentation of ticagrelor intake within the prior 3 days
- Patients described below who require urgent reversal of the antiplatelet effects of ticagrelor:
Patients with uncontrolled major or life-threatening bleeding, requiring urgent reversal of the antiplatelet effects of ticagrelor. It is expected that enrolled patients would have characteristics similar to those described below:
- Potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise, e.g., systolic blood pressure < 90 mm Hg and signs or symptoms of low cardiac output not otherwise explained
- Bleeding in a critical organ or closed space, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular bleed with compartment syndrome
- Visible, uncontrolled bleeding associated with a corrected hemoglobin level < 8.0 g/dL, a fall in hemoglobin level of ≥ 2.0 g/dL (1.24 mmol/L) from a known baseline, or requirement for transfusion of 2 or more units of packed red blood cells (PRBC)
Patients requiring urgent surgery or invasive procedure when it is not medically advisable either to proceed urgently with impaired hemostasis or to delay the urgent procedure for 3 or more days due to the high risk of bleeding. These patients may typically be in any of the following clinical situations:
- Requires urgent surgery or invasive procedure known to be associated with a risk of significant bleeding (such as cardiac surgery, neurosurgery, or major orthopedic surgery)
- Requires urgent surgery or invasive procedure that may have an adverse procedural outcome if hemostasis is impaired (such as neurological, spinal, ophthalmological, urological, or orthopedic surgery)
- At risk of experiencing life-threatening events, such as, shock, myocardial infarction, or stroke, if significant intraoperative or postoperative bleeding occurs (such as in elderly patients or patients with underlying cardiac or pulmonary disease who have limited cardiopulmonary reserve)
Exclusion Criteria:
- Known sensitivity or contraindication to PB2452 or any of its excipients
- Patients in whom ticagrelor reversal is not considered urgent, e.g., patients with stable or non-acute conditions who have low hemoglobin due to chronic, low-grade gastrointestinal bleeding or who have stable, remote, or asymptomatic intracranial hemorrhage
- Patients expected to be clinically unsalvageable, such as, patients with end-stage cancer or patients with overwhelming sepsis
- Any condition which, in the opinion of the investigator, would make it unsafe or unsuitable for the patients to participate in this study. This includes assessment of likelihood to cooperate with study follow-up visits and procedures. Known pregnancy may be exclusionary in some regions or countries as directed by national health authorities and/or local Institutional Review Boards/Ethics Committees
- Known use of clopidogrel, prasugrel or ticlopidine within 5 days of study drug administration; known use of antiplatelet GPIIb/IIIa inhibitors, or cangrelor within 5 half-lives of expected study drug administration; or known use of warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban within 5 half-lives of expected study drug administration
- Known recent use (< 5 day) of vitamin K, prothrombin complex concentrate, recombinant factor VIIa, idarucizumab, or andexanet-alfa (coagulation factor Xa (recombinant), inactivated-zhzo)
Sites / Locations
- Providence St. Jude Medical Center
- MedStar Health Research InstituteRecruiting
- Baptist Medical Center
- University of Florida Health, JacksonvilleRecruiting
- Mayo ClinicRecruiting
- Intercoastal Medical Group, Inc.Recruiting
- University of Iowa Hospitals and ClinicsRecruiting
- University of KentuckyRecruiting
- Ochsner LSU Health ShreveportRecruiting
- Sinai Hospital of Baltimore
- White Oak Medical Center
- Henry Ford HospitalRecruiting
- Beaumont Hospital, Royal Oak
- North Kansas City HospitalRecruiting
- Cox Medical CentersRecruiting
- East Carolina University
- Duke Heart Center at Southeastern HealthRecruiting
- Sanford Medical Center FargoRecruiting
- Ascension St. John Clinical Research InstituteRecruiting
- Allegheny General Hospital
- Crozer Chester Medical Center
- Rhode Island HospitalRecruiting
- Stern Cardiovascular Foundation, Inc.Recruiting
- Johnson City Medical CenterRecruiting
- University of Tennessee Medical CenterRecruiting
- JPS Health NetworkRecruiting
- Klinische Abteilung für Innere Medizin 3 Universitätsklinikum St. PöltenRecruiting
- Klinik Ottakring 3rd Med Dept, Cardiology and Intensive Care MedicineRecruiting
- Algemeen Stedelijk Ziekenhuis (ASZ) Study Center CardiologyRecruiting
- Ziekenhuis Oost-Limburg Study Center Intensive CareRecruiting
- AZ Sint-Jan Brugge-Oostende AV Poli CardiologieRecruiting
- University Hospital Antwerp Cardiology Department - Clinical TrialsRecruiting
- Jessa Hospital Hartcentrum Hasselt Research CenterRecruiting
- University Hospital Leuven, Universitair Ziekenhuis Leuven Dienst Bloedings- en VaatziektenRecruiting
- Foothills Medical CentreRecruiting
- University of Alberta HospitalRecruiting
- St. Paul's HospitalRecruiting
- St. Boniface HospitalRecruiting
- Saint John Regional HospitalRecruiting
- William Osler Health System - Brampton Civic Hospital
- Hamilton Health Sciences CentreRecruiting
- Kingston Health Sciences CentreRecruiting
- York PCI Group, Inc.Recruiting
- Oakville Trafalgar Memorial HospitalRecruiting
- University of Ottawa Heart InstituteRecruiting
- St. Michael's Hospital, Unity Health TorontoRecruiting
- Toronto General HospitalRecruiting
- Montreal Heart InstituteRecruiting
- McGill University Health CenterRecruiting
- Centre intégré universitaire de santé et de services sociaux du Nord-de-l'lle-de-Montréal (CIUSSS NIM)/Hopital du Sacré-Coeur-de-MontréalRecruiting
- Institut universitaire de cardiologie et de pneumologie de Quebec - Universite LavalRecruiting
- Beijing Anzhen Hospital, Capital Medical UniversityRecruiting
- China-Japan Friendship HospitalRecruiting
- Peking University First Hospital
- Beijing Chaoyang Hospital, Capital Medical University
- Peking University People's HospitalRecruiting
- Peking University Third HospitalRecruiting
- Lanzhou University Second Hospital
- The First Affiliated Hospital of Zhengzhou University
- The Central Hospital of WuhanRecruiting
- Huai'an First People's HospitalRecruiting
- The First Hospital of Jilin UniversityRecruiting
- Medidata
- First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
- Tianjin Medical University General HospitalRecruiting
- Tianjin Chest HospitalRecruiting
- Sir Run Run Shaw Hospital, Zhejiang University School of MedicineRecruiting
- MedidataRecruiting
- Zhejiang Provincial People's HospitalRecruiting
- CHU de Lille Service USIC, Institut Coeur PoumonRecruiting
- Assistance Publique-Hopitaux de Paris (AP-HP) Pitie-Salpetriere HospitalRecruiting
- Bichat Hospital, Service de CardiologieRecruiting
- CHRU de Tours - Hopital Trousseau Service de Cardiologie-USCI 2 eme etageRecruiting
- ASST Monza - Ospedale San GerardoRecruiting
- Azienda Ospedaliero-Universitaria di Parma CardiologiaRecruiting
- Istituto Clinico Humanitas UO Cardiologia Clinica e InterventisticaRecruiting
- Medisch Spectrum TwenteRecruiting
- St Antonius HospitalRecruiting
- Complejo Hospitalario Universitario A CorunaRecruiting
- Hospital Universitario Vall d'HebronRecruiting
- Hospital Universitario 12 de Octubre, Residencia generalRecruiting
- Hospital Clinico San Carlos - Instituto Cardiovascular (ICV)
- Hospital Universitario Vírgen de la VictoriaRecruiting
- Hospital Universitario Virgen MacarenaRecruiting
- Skane University Hospital, Department of CardiologyRecruiting
- Region Uppsala, Akademiska Hospital Cardio and Pulmonary Medicine and Clinical PhysiologyRecruiting
- Universitatsspital Basel Department of CardiologyRecruiting
- Cardiocentro TicinoRecruiting
- East and North Hertfordshire, NHS Trust, Lister Cardiac Research Office, Cardiology Green Zone, Lister HospitalRecruiting
- Sheffield Teaching Hospitals, NHS Foundation Trust, Northern General HospitalRecruiting
Arms of the Study
Arm 1
Experimental
Bentracimab (PB2452) Infusion - Open Label Active Drug
Bentracimab (PB2452) 18 g Intravenous Infusion over a 16 hour duration. Patients with uncontrolled major or life-threatening bleeding. Bentracimab (PB2452) 18 g Intravenous Infusion over a 16 hour duration. For patients in need of urgent surgery or invasive procedure.