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

Acute Major Bleeding Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04867837
• Other study ID #: LEX-210
• Status: Recruiting
• Phase: Phase 3
• Start date: September 1, 2021
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: Octapharma
• Contact: Sigurd Knaub, PhD
• Phone: +41554512141
• Email: Sigurd.Knaub[@]octapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Major Bleeding
• Hemorrhage

Intervention

Drug:
• Octaplex
Four-factor prothrombin complex concentrate (4F-PCC)

Locations

Country	Name	City	State
Austria	Klinikum Klagenfurt am Wörthersee Anästhesiologie und Intensivmedizin	Klagenfurt
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Univeristy Clinical Hospital Mostar	Mostar
Bosnia and Herzegovina	Clinical Center University of Sarajevo	Sarajevo
Bosnia and Herzegovina	University Clinical Center Tuzla	Tuzla
Croatia	Clinical Hospital Dubrava	Zagreb
Croatia	University Hospital Centre Zagreb	Zagreb
France	Centre Hospitalier Universitaire Francois Mitterand	Dijon
Georgia	K.Eristavi National Center of Experimental and Clinical Surgery	Tbilisi
Georgia	LTS ,, Israel-Geoargian Medical Research clinic Helsicore"	Tbilisi
Georgia	New Hospitals	Tbilisi
Georgia	Pineo Medical Ecosystem	Tbilisi
Georgia	Tbilisi Institute of Medicine	Tbilisi
Germany	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
Italy	Ospedale Maggiore - IRCCS Istituto di Scienze Neurologiche di Bologna	Bologna
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milan
Italy	San Raffaele Hospital	Milano
Italy	Azienda Ospedaliero -Universitaria di Modena	Modena
Italy	Ospedale Santa Maria della Misericordia	Perugia
Italy	Azienda Ospedaliero-Universitaria Senese	Siena
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Lecznej	Leczna
Poland	Military Institute of Medicine	Warsaw
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Dr. Peset	Valencia
Turkey	Ankara University Faculty of Medicine	Ankara
Turkey	Inönü 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	Izmir
Turkey	Kahramanmaras Sütçü Imam University Faculty of Medicine	Kahramanmaras
Turkey	Ondokuz Mayis University Faculty of Medicine	Samsun
Ukraine	Public Non-profit Enterprise Clinical Emergency Care Hospital of Dnipro City Counsil	Dnipro
Ukraine	Public Non-profit Enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council	Ivano-Frankivsk
Ukraine	Public Non-profit Enterprise Regional Clinical Hospital of lvano-Frankivsk Regional 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
United Kingdom	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 States	Ascension Seton Medical Center Austin	Austin	Texas
United States	Dell Seton Medical Center at the University of Texas	Austin	Texas
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	The University of Florida	Gainesville	Florida
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	OU Health - University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	Oregon Health & Science University	Portland	Oregon
United States	Harbor-UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Austria,  Bosnia and Herzegovina,  Croatia,  France,  Georgia,  Germany,  Italy,  Poland,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Change in haematocrit (Hct)	Change in Hct from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Other	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
Other	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
Other	Change in platelet levels	Change in platelet levels from baseline to 48 hours after OCTAPLEX administration	48 hours after administration of drug
Other	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
Other	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
Other	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
Other	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
Other	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	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
Other	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
Other	Duration of Hospitalization	Duration of hospitalization	From admission to discharge, approximately 1-3 weeks
Primary	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	Change in endogenous thrombin potential (ETP)	Change in ETP as measured by thrombin generation assay	From baseline to 1 hour after administration of drug
Secondary	All-cause TEEs and All-cause Mortality	30-day event rate of thromboembolic events (TEEs) and all-cause mortality	30 days
Secondary	Occurrence of Adverse Events (AEs)	Occurrence of any AEs from start of OCTAPLEX administration until end of study	From IMP infusion until Day 30
Secondary	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
Secondary	Pulse	Pulse during a 48-hour follow-up period after OCTAPLEX administration and at discharge	From day of IMP infusion until Day 30
Secondary	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
Secondary	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