Clinical trial NCT04867837: Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor
Official title: Study of Four-factor Prothrombin Complex Concentrate, OCTAPLEX, in Patients With Acute Major Bleeding on Direct Oral Anticoagulant (DOAC) Therapy With Factor Xa Inhibitor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Major Bleeding
Keywords: Direct Oral Anticoagulant
Factor Xa Inhibitor
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2021-04-30
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Aged ≥18 years
3. 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
4. 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

Exclusion Criteria:

1. Patients with 'Do not resuscitate' (DNR) orders
2. Patients with acute trauma for which reversal of DOAC therapy with factor Xa inhibitor alone would not be expected to control the bleeding event
3. Hgb decrease without accompanying evidence of source of bleeding
4. Acute coronary syndrome, ischaemic stroke or venous thromboembolism (VTE) within the preceding 3 months
5. Patients with a history, within the last 3 months, of disseminated intravascular coagulation (DIC) or hyperfibrinolysis
6. Patients with a known congenital bleeding disorder
7. 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
8. Known hypersensitivity to plasma-derived products or heparin
9. 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)
10. 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
11. Patients on enoxaparin therapy for thromboembolic prophylaxis
12. 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)
13. 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)
14. 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
15. Patients who are pregnant or breastfeeding at the time of enrollment
16. Patients previously enrolled in this study
17. Patients participating in another interventional clinical treatment study currently or during the past 1 month prior to study inclusion

Primary outcomes:
measure: Hemostatic efficacy
timeFrame: Within 24 hours after the start of initial management
Secondary outcomes:
measure: Change in endogenous thrombin potential (ETP)
timeFrame: From baseline to 1 hour after administration of drug
measure: All-cause TEEs and All-cause Mortality
timeFrame: 30 days
measure: Occurrence of Adverse Events (AEs)
timeFrame: From IMP infusion until Day 30
measure: Body Temperature
timeFrame: From day of IMP infusion until Day 30
measure: Pulse
timeFrame: From day of IMP infusion until Day 30
measure: Respiration rate
timeFrame: From day of IMP infusion until Day 30
measure: Blood pressure
timeFrame: From day of IMP infusion until Day 30
Other outcomes:
measure: Change in Hgb
timeFrame: 48 hours after administration of drug
measure: Change in haematocrit (Hct)
timeFrame: 48 hours after administration of drug
measure: Change in red blood cell (RBC) levels
timeFrame: 48 hours after administration of drug
measure: Change in white blood cell (WBC) levels
timeFrame: 48 hours after administration of drug
measure: Change in platelet levels
timeFrame: 48 hours after administration of drug
measure: Change in prothrombin time (PT)
timeFrame: 24 hours after administration of drug
measure: Change in activated partial thromboplastin time (aPTT)
timeFrame: 24 hours after administration of drug
measure: Change in Coagulation Parameters
timeFrame: 24 hour follow-up period
measure: Number of packed RBC concentrate (pRBC) transfusion
timeFrame: 48 hours after administration of drug
measure: Number of pRBC Units Transfused
timeFrame: 48-hour follow-up period
measure: Other Blood Products Used
timeFrame: 48-hour follow-up period
measure: Use of Haemostatic Agents
timeFrame: 48 hours after administration of drug
measure: Duration of Hospitalization
timeFrame: From admission to discharge, approximately 1-3 weeks
Locations:
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Gainesville
country: United States
facility: The University of Florida
state: Florida
city: West Palm Beach
country: United States
facility: St. Mary's Medical Center
state: Florida
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Oklahoma City
country: United States
facility: OU Health - University of Oklahoma Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Austin
country: United States
facility: Ascension Seton Medical Center Austin
state: Texas
city: Austin
country: United States
facility: Dell Seton Medical Center at the University of Texas
state: Texas
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee Anästhesiologie und Intensivmedizin
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska
city: Mostar
country: Bosnia and Herzegovina
facility: Univeristy Clinical Hospital Mostar
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Center University of Sarajevo
city: Tuzla
country: Bosnia and Herzegovina
facility: University Clinical Center Tuzla
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Francois Mitterand
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem
city: Tbilisi
country: Georgia
facility: Tbilisi Institute of Medicine
city: Tbilisi
country: Georgia
facility: LTS ,, Israel-Geoargian Medical Research clinic Helsicore"
city: Tbilisi
country: Georgia
facility: New Hospitals
city: Tbilisi
country: Georgia
facility: K.Eristavi National Center of Experimental and Clinical Surgery
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen, Klinik fuer Anaesthesiologie
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin-Hufelandstraße
city: Frankfurt am main
country: Germany
facility: Universitaetsklinikum Frankfurt - Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital Neurologische Universitätsklinik
city: Tübingen
country: Germany
facility: Universitatsklinikum Tubingen Hertie-lnstitut fur klinische Hirnforschung (HIH) / Neurologische Universitatsklinik
city: Bologna
country: Italy
facility: Ospedale Maggiore - IRCCS Istituto di Scienze Neurologiche di Bologna
city: Milano
country: Italy
facility: San Raffaele Hospital
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliero -Universitaria di Modena
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Siena
country: Italy
facility: Azienda Ospedaliero-Universitaria Senese
city: Iława
country: Poland
facility: Ośrodek Badań Klinicznych BD Research
city: Kraków
country: Poland
facility: Clinical Research Center at Special Hospital Stefan Zeromski
city: Warsaw
country: Poland
facility: Military Institute of Medicine
city: Łęczna
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej w Łęcznej
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Adana
country: Turkey
facility: SBU Adana City Education and Research Hospital
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine
city: Battalgazi
country: Turkey
facility: İnönü University Faculty of Medicine
city: Bursa
country: Turkey
facility: Health Sciences University Bursa High Specialization Training and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Faculty of Medicine Department of Internal Diseases, Division of Hematology
city: İzmir
country: Turkey
facility: Ege University Faculty of Medicine
city: Kahramanmaraş
country: Turkey
facility: Kahramanmaraş Sütçü İmam University Faculty of Medicine
city: Mersin
country: Turkey
facility: Mersin University Faculty of Medicine
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University Faculty of Medicine
city: Trabzon
country: Turkey
facility: Karadeniz Technical University
city: Dnipro
country: Ukraine
facility: Public Non-profit Enterprise Clinical Emergency Care Hospital of Dnipro City Counsil
city: Ivano-Frankivsk
country: Ukraine
facility: Public Non-profit Enterprise Regional Clinical Hospital of lvano-Frankivsk Regional Council
city: Ivano-Frankivsk
country: Ukraine
facility: Public Non-profit Enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council
city: Kropyvnytskyi
country: Ukraine
facility: Medical and Diagnostic Center of Private Enterprise of Private Manufacturing Company "Acinus"
city: Kyiv
country: Ukraine
facility: Public Non-profit Enterprise Kyiv City Clinical Hospital #17 of Kyiv City Council Executive Body
city: Lviv
country: Ukraine
facility: Public Non-profit Enterprise of Lviv Regional Council Lviv Public non profit Regional Clinical Hospital
city: Basingstoke
country: United Kingdom
facility: North Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital
state: Hampshire
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: