Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor

Study of Four-factor Prothrombin Complex Concentrate, OCTAPLEX, in Patients With Acute Major Bleeding on Direct Oral Anticoagulant (DOAC) Therapy With Factor Xa Inhibitor

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Major Bleeding
• Intervention / Treatment: Drug: Octaplex

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sigurd Knaub, PhD; Phone Number: +41554512141; Email: Sigurd.Knaub@octapharma.com

Study Locations

• Austria
  • Klagenfurt, Austria, 9020
    • Terminated
    • Klinikum Klagenfurt am Wörthersee Anästhesiologie und Intensivmedizin
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • Terminated
    • University Clinical Centre of the Republic of Srpska
  • Mostar, Bosnia and Herzegovina, 88000
    • Terminated
    • Univeristy Clinical Hospital Mostar
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Active, not recruiting
    • Clinical Center University of Sarajevo
  • Tuzla, Bosnia and Herzegovina, 75000
    • Active, not recruiting
    • University Clinical Center Tuzla
• Croatia
  • Zagreb, Croatia, 10000
    • Terminated
    • University Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Terminated
    • Clinical Hospital Dubrava
• France
  • Dijon, France, 21000
    • Terminated
    • Centre Hospitalier Universitaire Francois Mitterand
• Georgia
  • Tbilisi, Georgia, 114
    • Recruiting
    • New Hospitals
  • Tbilisi, Georgia, 159
    • Recruiting
    • K.Eristavi National Center of Experimental and Clinical Surgery
  • Tbilisi, Georgia, 112
    • Recruiting
    • LTS ,, Israel-Geoargian Medical Research clinic Helsicore"
  • Tbilisi, Georgia, 00108
    • Recruiting
    • Pineo Medical Ecosystem
  • Tbilisi, Georgia, 00160
    • Recruiting
    • Tbilisi Institute of Medicine
• Germany
  • Aachen, Germany, 52074
    • Active, not recruiting
    • Universitaetsklinikum Aachen, Klinik fuer Anaesthesiologie
  • Erlangen, Germany, 91054
    • Recruiting
    • Universitätsklinikum Erlangen
  • Essen, Germany, D-45147
    • Recruiting
    • Universitaetsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin-Hufelandstraße
  • Frankfurt am Main, Germany, 60590
    • Recruiting
    • Universitaetsklinikum Frankfurt - Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie
  • Heidelberg, Germany, 69120
    • Recruiting
    • Heidelberg University Hospital Neurologische Universitätsklinik
  • Tübingen, Germany, Germany
    • Recruiting
    • Universitatsklinikum Tubingen Hertie-lnstitut fur klinische Hirnforschung (HIH) / Neurologische Universitatsklinik
• Italy
  • Bologna, Italy, 40133
    • Recruiting
    • Ospedale Maggiore - IRCCS Istituto di Scienze Neurologiche di Bologna
  • Milan, Italy, 20122
    • Terminated
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Milan, Italy, 20132
    • Terminated
    • San Raffaele Hospital
  • Modena, Italy, 41125
    • Active, not recruiting
    • Azienda Ospedaliero -Universitaria di Modena
  • Perugia, Italy, 06156
    • Recruiting
    • Ospedale Santa Maria Della Misericordia
  • Siena, Italy, 53100
    • Active, not recruiting
    • Azienda Ospedaliero-Universitaria Senese
• Poland
  • Iława, Poland, 14-200
    • Recruiting
    • Osrodek Badan Klinicznych Bd Research
  • Krakow, Poland, 31-913
    • Recruiting
    • Clinical Research Center at Special Hospital Stefan Zeromski
  • Warsaw, Poland, 04-141
    • Terminated
    • Military Institute of Medicine
  • Łęczna, Poland, 21-010
    • Recruiting
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej w Łęcznej
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 00261
    • Recruiting
    • Hospital Universitario La Paz
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politécnico La FE
  • Valencia, Spain, 46017
    • Active, not recruiting
    • Hospital Dr. Peset
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01370
    • Recruiting
    • SBU Adana City Education and Research Hospital
  • Ankara, Turkey (Türkiye), 6230
    • Recruiting
    • Ankara University Faculty of Medicine
  • Battalgazi, Turkey (Türkiye), 44280
    • Recruiting
    • Inonu University Faculty of Medicine
  • Bursa, Turkey (Türkiye), 16300
    • Recruiting
    • Health Sciences University Bursa High Specialization Training and Research Hospital
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • Istanbul University Istanbul Faculty of Medicine Department of Internal Diseases, Division of Hematology
  • Izmir, Turkey (Türkiye), 35100
    • Recruiting
    • Ege University Faculty of Medicine
  • Kahramanmaraş, Turkey (Türkiye), 46040
    • Recruiting
    • Kahramanmaraş Sütçü İmam University Faculty of Medicine
  • Mersin, Turkey (Türkiye), 33343
    • Recruiting
    • Mersin University Faculty of Medicine
  • Samsun, Turkey (Türkiye), 55280
    • Recruiting
    • Ondokuz Mayıs University Faculty of Medicine
  • Trabzon, Turkey (Türkiye), 61080
    • Recruiting
    • Karadeniz Technical University
• Ukraine
  • Dnipro, Ukraine, 49006
    • Recruiting
    • Public Non-profit Enterprise Clinical Emergency Care Hospital of Dnipro City Counsil
  • Ivano-Frankivsk, Ukraine, 76008
    • Active, not recruiting
    • Public Non-profit Enterprise Regional Clinical Hospital of lvano-Frankivsk Regional Council
  • Ivano-Frankivsk, Ukraine, 76025
    • Active, not recruiting
    • Public Non-profit Enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council
  • Kropyvnytskyi, Ukraine, 26006
    • Recruiting
    • Medical and Diagnostic Center of Private Enterprise of Private Manufacturing Company "Acinus"
  • Kyiv, Ukraine, 01133
    • Not yet recruiting
    • Public Non-profit Enterprise Kyiv City Clinical Hospital #17 of Kyiv City Council Executive Body
  • Lviv, Ukraine, 79010
    • Recruiting
    • Public Non-profit Enterprise of Lviv Regional Council Lviv Public non profit Regional Clinical Hospital
• United Kingdom
  • Nottingham, United Kingdom, NG51PB
    • Terminated
    • Nottingham University Hospital
  • Southampton, United Kingdom, SO16 SYD
    • Terminated
    • Southampton General Hospital
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Terminated
      • North Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital
• United States
  • California
    • Torrance, California, United States, 90509
      • Terminated
      • Harbor-UCLA Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • The University of Florida
    • West Palm Beach, Florida, United States, 33407
      • Recruiting
      • St. Mary's Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Terminated
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Terminated
      • Hennepin County Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Terminated
      • University of Mississippi Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Terminated
      • OU Health - University of Oklahoma Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Terminated
      • Oregon Health & Science University
  • Texas
    • Austin, Texas, United States, 78712
      • Terminated
      • Ascension Seton Medical Center Austin
    • Austin, Texas, United States, 78712
      • Terminated
      • Dell Seton Medical Center at The University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Octaplex Low-dose; Participants to receive 1 Octaplex infusion intravenously	Drug: Octaplex; Four-factor prothrombin complex concentrate (4F-PCC)
Experimental: Octaplex High-dose; Participants to receive 1 Octaplex infusion intravenously	Drug: Octaplex; Four-factor prothrombin complex concentrate (4F-PCC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemostatic efficacy	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	Within 24 hours after the start of initial management

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in endogenous thrombin potential (ETP)	Change in ETP as measured by thrombin generation assay	From baseline to 1 hour after administration of drug
Body Temperature	Temperature measured during a 48-hour follow-up period after OCTAPLEX administration and at discharge	From day of IMP infusion until Day 30
Pulse	Pulse during a 48-hour follow-up period after OCTAPLEX administration and at discharge	From day of IMP infusion until Day 30
Respiration rate	Respiration rate during a 48-hour follow-up period after OCTAPLEX administration and at discharge	From day of IMP infusion until Day 30
Blood pressure	Blood pressure during a 48-hour follow-up period after OCTAPLEX administration and at discharge	From day of IMP infusion until Day 30
All-cause TEEs and All-cause Mortality	30-day event rate of thromboembolic events (TEEs) and all-cause mortality	30 days
Occurrence of Adverse Events (AEs)	Occurrence of any AEs from start of OCTAPLEX administration until end of study	From IMP infusion until Day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in haematocrit (Hct)	Change in Hct from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Change in red blood cell (RBC) levels	Change in RBC levels from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Change in white blood cell (WBC) levels	Change in WBC levels from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Change in platelet levels	Change in platelet levels from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Change in prothrombin time (PT)	Change in prothrombin time from baseline during a 24-hour follow-up period after OCTAPLEX administration	24 hours after administration of drug
Change in activated partial thromboplastin time (aPTT)	Change in aPTT from baseline during a 24-hour follow-up period after OCTAPLEX administration	24 hours after administration of drug
Change in Hgb	Change in haematologic parameters based on complete blood count (CBC), i.e., Hgb, haematocrit (Hct), red blood cells (RBC), white blood cells (WBC), platelets, from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Change in Coagulation Parameters	Change in coagulation parameters (international normalised ratio [INR], prothrombin time [PT], activated partial thromboplastin time [aPTT], coagulation factors II, VII, IX, and X levels) from baseline during a 24-hour follow-up period after OCTAPLEX administration	24 hour follow-up period
Number of packed RBC concentrate (pRBC) transfusion	The number of patients receiving one or more pRBC transfusions during a 48-hour follow-up period after OCTAPLEX administration.	48 hours after administration of drug
Number of pRBC Units Transfused	The number of pRBC units transfused per patient during a 48-hour follow-up period after OCTAPLEX administration	48-hour follow-up period
Other Blood Products Used	The use of other blood products and/or haemostatic agents during a 48-hour follow-up period after OCTAPLEX administration	48-hour follow-up period
Use of Haemostatic Agents	The use of haemostatic agents during a 48-hour follow-up period after OCTAPLEX administration.	48 hours after administration of drug
Duration of Hospitalization	Duration of hospitalization	From admission to discharge, approximately 1-3 weeks

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): April 30, 2021

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Direct Oral Anticoagulant; Factor Xa Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; prothrombin complex concentrates
• Other Study ID Numbers: LEX-210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No