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

NCT04867837 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: LEX-210
• Study Type: interventional
• Target: 260
• Locations: 13 countries
• Sites: 63

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.

Conditions

Acute Major Bleeding

Keywords

Direct Oral Anticoagulant; Factor Xa Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change in endogenous thrombin potential (ETP)

  From baseline to 1 hour after administration of drug

• All-cause TEEs and All-cause Mortality

  30 days

• Occurrence of Adverse Events (AEs)

  From IMP infusion until Day 30

• Body Temperature

  From day of IMP infusion until Day 30

• Pulse

  From day of IMP infusion until Day 30

Other Outcomes (13)

• Change in Hgb

  48 hours after administration of drug

• Change in haematocrit (Hct)

  48 hours after administration of drug

• Change in red blood cell (RBC) levels

  48 hours after administration of drug

Study Arms (2)

Octaplex Low-dose

EXPERIMENTAL

Participants to receive 1 Octaplex infusion intravenously

Drug: Octaplex

Octaplex High-dose

EXPERIMENTAL

Participants to receive 1 Octaplex infusion intravenously

Drug: Octaplex

Interventions

Octaplex DRUG

Four-factor prothrombin complex concentrate (4F-PCC)

Octaplex High-dose; Octaplex Low-dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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
• \- Symptomatic bleeding in critical organs (intracranial, intraspinal, intraocular, gastrointestinal, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome)
• \- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Octapharma: lead

Study Sites (63)

Harbor-UCLA Medical Center

Torrance, California, 90509, United States

TERMINATED

The University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

TERMINATED

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

TERMINATED

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

TERMINATED

OU Health - University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

TERMINATED

Oregon Health & Science University

Portland, Oregon, 97239, United States

TERMINATED

Ascension Seton Medical Center Austin

Austin, Texas, 78712, United States

TERMINATED

Dell Seton Medical Center at the University of Texas

Austin, Texas, 78712, United States

TERMINATED

Klinikum Klagenfurt am Wörthersee Anästhesiologie und Intensivmedizin

Klagenfurt, 9020, Austria

TERMINATED

University Clinical Centre of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

TERMINATED

Univeristy Clinical Hospital Mostar

Mostar, 88000, Bosnia and Herzegovina

TERMINATED

Clinical Center University of Sarajevo

Sarajevo, 71000, Bosnia and Herzegovina

ACTIVE NOT RECRUITING

University Clinical Center Tuzla

Tuzla, 75000, Bosnia and Herzegovina

ACTIVE NOT RECRUITING

Clinical Hospital Dubrava

Zagreb, 10000, Croatia

TERMINATED

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

TERMINATED

Centre Hospitalier Universitaire Francois Mitterand

Dijon, 21000, France

TERMINATED

Pineo Medical Ecosystem

Tbilisi, 00108, Georgia

RECRUITING

Tbilisi Institute of Medicine

Tbilisi, 00160, Georgia

RECRUITING

LTS ,, Israel-Geoargian Medical Research clinic Helsicore"

Tbilisi, 112, Georgia

RECRUITING

New Hospitals

Tbilisi, 114, Georgia

RECRUITING

K.Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, 159, Georgia

RECRUITING

Universitaetsklinikum Aachen, Klinik fuer Anaesthesiologie

Aachen, 52074, Germany

ACTIVE NOT RECRUITING

Universitatsklinikum Erlangen

Erlangen, 91054, Germany

RECRUITING

Universitaetsklinikum Essen, Klinik für Anästhesiologie und Intensivmedizin-Hufelandstraße

Essen, D-45147, Germany

RECRUITING

Universitaetsklinikum Frankfurt - Klinik fuer Anaesthesiologie, Intensivmedizin und Schmerztherapie

Frankfurt am Main, 60590, Germany

RECRUITING

Heidelberg University Hospital Neurologische Universitätsklinik

Heidelberg, 69120, Germany

RECRUITING

Universitatsklinikum Tubingen Hertie-lnstitut fur klinische Hirnforschung (HIH) / Neurologische Universitatsklinik

Tübingen, Germany, Germany

RECRUITING

Ospedale Maggiore - IRCCS Istituto di Scienze Neurologiche di Bologna

Bologna, 40133, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

TERMINATED

San Raffaele Hospital

Milan, 20132, Italy

TERMINATED

Azienda Ospedaliero -Universitaria di Modena

Modena, 41125, Italy

ACTIVE NOT RECRUITING

Ospedale Santa Maria della Misericordia

Perugia, 06156, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Senese

Siena, 53100, Italy

ACTIVE NOT RECRUITING

Ośrodek Badań Klinicznych BD Research

Iława, 14-200, Poland

RECRUITING

Clinical Research Center at Special Hospital Stefan Zeromski

Krakow, 31-913, Poland

RECRUITING

Military Institute of Medicine

Warsaw, 04-141, Poland

TERMINATED

Samodzielny Publiczny Zakład Opieki Zdrowotnej w Łęcznej

Łęczna, 21-010, Poland

RECRUITING

Hospital Universitario La Paz

Madrid, 00261, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Dr. Peset

Valencia, 46017, Spain

ACTIVE NOT RECRUITING

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

RECRUITING

SBU Adana City Education and Research Hospital

Adana, 01370, Turkey (Türkiye)

RECRUITING

Ankara University Faculty of Medicine

Ankara, 6230, Turkey (Türkiye)

RECRUITING

İnönü University Faculty of Medicine

Battalgazi, 44280, Turkey (Türkiye)

RECRUITING

Health Sciences University Bursa High Specialization Training and Research Hospital

Bursa, 16300, Turkey (Türkiye)

RECRUITING

Istanbul University Istanbul Faculty of Medicine Department of Internal Diseases, Division of Hematology

Istanbul, 34093, Turkey (Türkiye)

RECRUITING

Ege University Faculty of Medicine

Izmir, 35100, Turkey (Türkiye)

RECRUITING

Kahramanmaraş Sütçü İmam University Faculty of Medicine

Kahramanmaraş, 46040, Turkey (Türkiye)

RECRUITING

Mersin University Faculty of Medicine

Mersin, 33343, Turkey (Türkiye)

RECRUITING

Ondokuz Mayıs University Faculty of Medicine

Samsun, 55280, Turkey (Türkiye)

RECRUITING

Karadeniz Technical University

Trabzon, 61080, Turkey (Türkiye)

RECRUITING

Public Non-profit Enterprise Clinical Emergency Care Hospital of Dnipro City Counsil

Dnipro, 49006, Ukraine

RECRUITING

Public Non-profit Enterprise Regional Clinical Hospital of lvano-Frankivsk Regional Council

Ivano-Frankivsk, 76008, Ukraine

ACTIVE NOT RECRUITING

Public Non-profit Enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council

Ivano-Frankivsk, 76025, Ukraine

ACTIVE NOT RECRUITING

Medical and Diagnostic Center of Private Enterprise of Private Manufacturing Company "Acinus"

Kropyvnytskyi, 26006, Ukraine

RECRUITING

Public Non-profit Enterprise Kyiv City Clinical Hospital #17 of Kyiv City Council Executive Body

Kyiv, 01133, Ukraine

NOT YET RECRUITING

Public Non-profit Enterprise of Lviv Regional Council Lviv Public non profit Regional Clinical Hospital

Lviv, 79010, Ukraine

RECRUITING

North Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital

Basingstoke, Hampshire, RG24 9NA, United Kingdom

TERMINATED

Nottingham University Hospital

Nottingham, NG51PB, United Kingdom

TERMINATED

Southampton General Hospital

Southampton, SO16 SYD, United Kingdom

TERMINATED

MeSH Terms

Interventions

prothrombin complex concentrates

Central Study Contacts

Sigurd Knaub, PhD

CONTACT

+41554512141; Sigurd.Knaub@octapharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 30, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); DE (6); ES (5); GE (5); PL (4); US (10); FR (1); UA (6); GB (3); IT (6); BO (4); CR (2); TU (10)