Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor
- Registration Number
- NCT04867837
- Lead Sponsor
- Octapharma
- Brief Summary
This is a multicentre, prospective, randomised, double-blinded, group-sequential, parallel-group, adaptive design, phase 3 study to demonstrate the haemostatic efficacy and safety of four-factor prothrombin complex concentrate, OCTAPLEX, in patients with acute major bleeding on DOAC therapy with factor Xa inhibitor. Patients will be randomised 1:1 to either of two study groups: low-dose vs. high-dose OCTAPLEX.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 260
-
Patients on oral factor Xa inhibitor therapy and with known or suspected baseline anti-factor Xa activity of at least 100 ng/mL:
- Patients who received or who are believed by the investigator to have received a dose of oral factor Xa inhibitor and who have a baseline anti- factor Xa activity of at least 100 ng/mL according to the locally available test (e.g., chromogenic assay) performed outside of the study as part of standard of care
OR
- Patients who received or who are believed by the investigator to have received their latest dose of oral factor Xa inhibitor (e.g., rivaroxaban ≥10 mg, apixaban ≥2.5 mg, edoxaban ≥30 mg) ≤8 hours prior to enrolment
OR
-Patients who received or who are believed by the investigator to have received their latest dose of oral factor Xa inhibitor (e.g., rivaroxaban ≥10 mg, apixaban ≥2.5 mg, edoxaban ≥30 mg) >8 hours prior to enrolment or at an unknown time, but for whom the investigator suspects a baseline anti- factor Xa activity of at least 100 ng/mL and assesses that the administration of OCTAPLEX is clinically indicated
-
Aged ≥18 years
-
Patients who have given written informed consent or for whom written informed consent has been obtained from the patient's legally authorised representative on their behalf -Wherever possible, prospective written informed consent will be obtained before enrolment from the patient or, if they are incapable of providing it, from their legally authorised representative
-If prospective written informed consent is not possible, deferred consent procedures will be permitted outside the US if approved by the local ethics committee or otherwise permitted under local regulations
-When deferred consent procedures are used outside the US, written informed consent should be obtained from the patient as soon as they recover the capacity to provide it, or otherwise from their legally authorised representative
-
Patients who have acute major bleeding defined as follows:
- Bleeding that is life-threatening or uncontrolled, e.g., with signs or symptoms of haemodynamic compromise, such as severe hypotension, poor skin perfusion, or low cardiac output that cannot be otherwise explained
OR
- Symptomatic bleeding in critical organs (intracranial, intraspinal, intraocular, gastrointestinal, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome)
OR
- Acute overt bleeding associated with a fall in haemoglobin (Hgb) level of ≥2 g/dL, OR a Hgb level ≤8 g/dL if no baseline Hgb level is available, OR in the opinion of the investigator that the patient's Hgb level will fall to ≤8 g/dL with resuscitation
- Patients with 'Do not resuscitate' (DNR) orders
- Patients with acute trauma for which reversal of DOAC therapy with factor Xa inhibitor alone would not be expected to control the bleeding event
- Hgb decrease without accompanying evidence of source of bleeding
- Acute coronary syndrome, ischaemic stroke or venous thromboembolism (VTE) within the preceding 3 months
- Patients with a history, within the last 3 months, of disseminated intravascular coagulation (DIC) or hyperfibrinolysis
- Patients with a known congenital bleeding disorder
- Known inhibitors to coagulation factors II, VII, IX, or X; heparin-induced, type II thrombocytopenia; or immunoglobulin A (IgA) deficiency with known antibodies against IgA
- Known hypersensitivity to plasma-derived products or heparin
- Patients who received haemostatic agents, including plasma, platelets, PCC, activated PCC (aPCC), recombinant factor VIIa, or recombinant factor Xa inactivated-zhzo (andexanet alfa), for the current bleeding event prior to enrolment (antifibrinolytic drugs and local haemostatic agents are allowed)
- Patients who received ticlopidine within 14 days, prasugrel within 7 days, ticagrelor within 5 days, dipyridamole within 1 day or cangrelor within 1 hour preceding the bleeding event
- Patients on enoxaparin therapy for thromboembolic prophylaxis
- A score of less than 7 on the Glasgow Coma Scale in non-intubated patients or an estimated intracerebral haematoma volume of more than 60 mL. (Patients intubated or sedated at the time of screening may be enrolled if intubation or sedation were done for non-neurologic reasons)
- Patients with expected survival of less than 24 hours, in the opinion of the investigator (in collaboration with other medical experts as appropriate per usual local practice)
- Patients scheduled to undergo surgery in less than 12 hours, with the exception of minor surgeries and invasive procedures which are allowed for diagnostic or therapeutic reasons or if intended to address a second (non-index) bleeding event
- Patients who are pregnant or breastfeeding at the time of enrollment
- Patients previously enrolled in this study
- Patients participating in another interventional clinical treatment study currently or during the past 1 month prior to study inclusion
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Octaplex High-dose Octaplex Participants to receive 1 Octaplex infusion intravenously Octaplex Low-dose Octaplex Participants to receive 1 Octaplex infusion intravenously
- Primary Outcome Measures
Name Time Method Hemostatic efficacy Within 24 hours after the start of initial management Binary outcome of effective (rating of excellent or good) or non-effective (rating of poor/none) in management of major bleeding events as assessed by the Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) according to predefined criteria
- Secondary Outcome Measures
Name Time Method Occurrence of Adverse Events (AEs) From IMP infusion until Day 30 Occurrence of any AEs from start of OCTAPLEX administration until end of study
Body Temperature From day of IMP infusion until Day 30 Temperature measured during a 48-hour follow-up period after OCTAPLEX administration and at discharge
Pulse From day of IMP infusion until Day 30 Pulse during a 48-hour follow-up period after OCTAPLEX administration and at discharge
Respiration rate From day of IMP infusion until Day 30 Respiration rate during a 48-hour follow-up period after OCTAPLEX administration and at discharge
Change in endogenous thrombin potential (ETP) From baseline to 1 hour after administration of drug Change in ETP as measured by thrombin generation assay
All-cause TEEs and All-cause Mortality 30 days 30-day event rate of thromboembolic events (TEEs) and all-cause mortality
Blood pressure From day of IMP infusion until Day 30 Blood pressure during a 48-hour follow-up period after OCTAPLEX administration and at discharge
Trial Locations
- Locations (58)
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
SBU Adana City Education and Research Hospital
🇹🇷Adana, Turkey
Mersin University Faculty of Medicine
🇹🇷Mersin, Turkey
Karadeniz Technical University
🇹🇷Trabzon, Turkey
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
The University of Florida
🇺🇸Gainesville, Florida, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
OU Health - University of Oklahoma Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University Clinical Center Tuzla
🇧🇦Tuzla, Bosnia and Herzegovina
Ascension Seton Medical Center Austin
🇺🇸Austin, Texas, United States
Dell Seton Medical Center at the University of Texas
🇺🇸Austin, Texas, United States
Clinical Center University of Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
Klinikum Klagenfurt am Wörthersee Anästhesiologie und Intensivmedizin
🇦🇹Klagenfurt, Austria
University Clinical Centre of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Univeristy Clinical Hospital Mostar
🇧🇦Mostar, Bosnia and Herzegovina
Clinical Hospital Dubrava
🇭🇷Zagreb, Croatia
University Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Centre Hospitalier Universitaire Francois Mitterand
🇫🇷Dijon, France
Pineo Medical Ecosystem
🇬🇪Tbilisi, Georgia
Tbilisi Institute of Medicine
🇬🇪Tbilisi, Georgia
LTS ,, Israel-Geoargian Medical Research clinic Helsicore"
🇬🇪Tbilisi, Georgia
New Hospitals
🇬🇪Tbilisi, Georgia
K.Eristavi National Center of Experimental and Clinical Surgery
🇬🇪Tbilisi, Georgia
Universitaetsklinikum Aachen, Klinik fuer Anaesthesiologie
🇩🇪Aachen, Germany
Universitaetsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin-Hufelandstraße
🇩🇪Essen, Germany
Universitaetsklinikum Frankfurt - Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie
🇩🇪Frankfurt am main, Germany
Heidelberg University Hospital Neurologische Universitätsklinik
🇩🇪Heidelberg, Germany
Universitatsklinikum Tubingen Hertie-lnstitut fur klinische Hirnforschung (HIH) / Neurologische Universitatsklinik
🇩🇪Tübingen, Germany
Ospedale Maggiore - IRCCS Istituto di Scienze Neurologiche di Bologna
🇮🇹Bologna, Italy
San Raffaele Hospital
🇮🇹Milano, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Azienda Ospedaliero -Universitaria di Modena
🇮🇹Modena, Italy
Ospedale Santa Maria della Misericordia
🇮🇹Perugia, Italy
Azienda Ospedaliero-Universitaria Senese
🇮🇹Siena, Italy
Military Institute of Medicine
🇵🇱Warsaw, Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej w Łęcznej
🇵🇱Łęczna, Poland
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Dr. Peset
🇪🇸Valencia, Spain
Ankara University Faculty of Medicine
🇹🇷Ankara, Turkey
İnönü University Faculty of Medicine
🇹🇷Battalgazi, Turkey
Health Sciences University Bursa High Specialization Training and Research Hospital
🇹🇷Bursa, Turkey
Istanbul University Istanbul Faculty of Medicine Department of Internal Diseases, Division of Hematology
🇹🇷Istanbul, Turkey
Ege University Faculty of Medicine
🇹🇷İzmir, Turkey
Kahramanmaraş Sütçü İmam University Faculty of Medicine
🇹🇷Kahramanmaraş, Turkey
Ondokuz Mayıs University Faculty of Medicine
🇹🇷Samsun, Turkey
Public Non-profit Enterprise Clinical Emergency Care Hospital of Dnipro City Counsil
🇺🇦Dnipro, Ukraine
Public Non-profit Enterprise Regional Clinical Hospital of lvano-Frankivsk Regional Council
🇺🇦Ivano-Frankivsk, Ukraine
Public Non-profit Enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council
🇺🇦Ivano-Frankivsk, Ukraine
Medical and Diagnostic Center of Private Enterprise of Private Manufacturing Company "Acinus"
🇺🇦Kropyvnytskyi, Ukraine
Public Non-profit Enterprise Kyiv City Clinical Hospital #17 of Kyiv City Council Executive Body
🇺🇦Kyiv, Ukraine
Public Non-profit Enterprise of Lviv Regional Council Lviv Public non profit Regional Clinical Hospital
🇺🇦Lviv, Ukraine
North Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, Hampshire, United Kingdom
Nottingham University Hospital
🇬🇧Nottingham, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom