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

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ClinicalTrials.gov Identifier: NCT04867837
Recruitment Status : Recruiting
First Posted : April 30, 2021
Last Update Posted : May 9, 2024
Sponsor:
Information provided by (Responsible Party):
Octapharma

Tracking Information
First Submitted Date  ICMJE April 19, 2021
First Posted Date  ICMJE April 30, 2021
Last Update Posted Date May 9, 2024
Actual Study Start Date  ICMJE September 1, 2021
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2021)
Hemostatic efficacy [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2021)
Hemostatic efficacy [ Time Frame: Within 24 hours after start of infusion 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2024)
  • Change in endogenous thrombin potential (ETP) [ Time Frame: 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 [ Time Frame: 30 days ]
    30-day event rate of thromboembolic events (TEEs) and all-cause mortality
  • Occurrence of Adverse Events (AEs) [ Time Frame: From IMP infusion until Day 30 ]
    Occurrence of any AEs from start of OCTAPLEX administration until end of study
  • Body Temperature [ Time Frame: From day of IMP infusion until Day 30 ]
    Temperature measured during a 48-hour follow-up period after OCTAPLEX administration and at discharge
  • Pulse [ Time Frame: From day of IMP infusion until Day 30 ]
    Pulse during a 48-hour follow-up period after OCTAPLEX administration and at discharge
  • Respiration rate [ Time Frame: From day of IMP infusion until Day 30 ]
    Respiration rate during a 48-hour follow-up period after OCTAPLEX administration and at discharge
  • Blood pressure [ Time Frame: From day of IMP infusion until Day 30 ]
    Blood pressure during a 48-hour follow-up period after OCTAPLEX administration and at discharge
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2021)
  • Change in endogenous thrombin potential (ETP) [ Time Frame: From baseline to 1 hour after administration of drug ]
    Change in ETP as measured by thrombin generation assay
  • 30-Day thromboembolic events (TEEs) [ Time Frame: 30 days ]
    30-day event rate of TEEs
  • 30-Day all-cause mortality [ Time Frame: 30 days ]
    30 day event rate of all cause mortality events
  • Occurrence of adverse events (AEs) [ Time Frame: Within 48 hours after start of infusion of initial management ]
    Occurrence of any AEs during a 48-hour follow-up period after OCTAPLEX administration
  • Temperature [ Time Frame: Within 48 hours after start of infusion of initial management ]
    Temperature during a 48-hour follow-up period after OCTAPLEX administration
  • Pulse [ Time Frame: Within 48 hours after start of infusion of initial management ]
    Pulse during a 48-hour follow-up period after OCTAPLEX administration
  • Respiration rate [ Time Frame: Within 48 hours after start of infusion of initial management ]
    Respiration rate during a 48-hour follow-up period after OCTAPLEX administration
  • Blood pressure [ Time Frame: Within 48 hours after start of infusion of initial management ]
    Blood pressure during a 48-hour follow-up period after OCTAPLEX administration
Current Other Pre-specified Outcome Measures
 (submitted: February 28, 2024)
  • Change in Hgb [ Time Frame: 48 hours after administration of drug ]
    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
  • Change in haematocrit (Hct) [ Time Frame: 48 hours after administration of drug ]
    Change in Hct from baseline to 48 hours after OCTAPLEX administration
  • Change in red blood cell (RBC) levels [ Time Frame: 48 hours after administration of drug ]
    Change in RBC levels from baseline to 48 hours after OCTAPLEX administration
  • Change in white blood cell (WBC) levels [ Time Frame: 48 hours after administration of drug ]
    Change in WBC levels from baseline to 48 hours after OCTAPLEX administration
  • Change in platelet levels [ Time Frame: 48 hours after administration of drug ]
    Change in platelet levels from baseline to 48 hours after OCTAPLEX administration
  • Change in prothrombin time (PT) [ Time Frame: 24 hours after administration of drug ]
    Change in prothrombin time from baseline during a 24-hour follow-up period after OCTAPLEX administration
  • Change in activated partial thromboplastin time (aPTT) [ Time Frame: 24 hours after administration of drug ]
    Change in aPTT from baseline during a 24-hour follow-up period after OCTAPLEX administration
  • Change in Coagulation Parameters [ Time Frame: 24 hour follow-up period ]
    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
  • Number of packed RBC concentrate (pRBC) transfusion [ Time Frame: 48 hours after administration of drug ]
    The number of patients receiving one or more pRBC transfusions during a 48-hour follow-up period after OCTAPLEX administration.
  • Number of pRBC Units Transfused [ Time Frame: 48-hour follow-up period ]
    The number of pRBC units transfused per patient during a 48-hour follow-up period after OCTAPLEX administration
  • Other Blood Products Used [ Time Frame: 48-hour follow-up period ]
    The use of other blood products and/or haemostatic agents during a 48-hour follow-up period after OCTAPLEX administration
  • Use of Haemostatic Agents [ Time Frame: 48 hours after administration of drug ]
    The use of haemostatic agents during a 48-hour follow-up period after OCTAPLEX administration.
  • Duration of Hospitalization [ Time Frame: From admission to discharge, approximately 1-3 weeks ]
    Duration of hospitalization
Original Other Pre-specified Outcome Measures
 (submitted: April 29, 2021)
  • Change in Hgb [ Time Frame: 48 hours after administration of drug ]
    Change in Hgb from baseline to 48 hours after OCTAPLEX administration
  • Change in haematocrit (Hct) [ Time Frame: 48 hours after administration of drug ]
    Change in Hct from baseline to 48 hours after OCTAPLEX administration
  • Change in red blood cell (RBC) levels [ Time Frame: 48 hours after administration of drug ]
    Change in RBC levels from baseline to 48 hours after OCTAPLEX administration
  • Change in white blood cell (WBC) levels [ Time Frame: 48 hours after administration of drug ]
    Change in WBC levels from baseline to 48 hours after OCTAPLEX administration
  • Change in platelet levels [ Time Frame: 48 hours after administration of drug ]
    Change in platelet levels from baseline to 48 hours after OCTAPLEX administration
  • Change in prothrombin time (PT) [ Time Frame: 24 hours after administration of drug ]
    Change in prothrombin time from baseline during a 24-hour follow-up period after OCTAPLEX administration
  • Change in activated partial thromboplastin time (aPTT) [ Time Frame: 24 hours after administration of drug ]
    Change in aPTT from baseline during a 24-hour follow-up period after OCTAPLEX administration
  • Change in coagulation factors II, VII, IX and X levels [ Time Frame: 24 hours after administration of drug ]
    Change in coagulation factors from baseline during a 24-hour follow-up period after OCTAPLEX administration
  • Number of packed RBC concentrate (pRBC) transfusions [ Time Frame: 48 hours after administration of drug ]
    The number of patients receiving one or more pRBC transfusions during a 48-hour follow-up period after OCTAPLEX administration.
  • Number of pRBC units transfused [ Time Frame: 48 hours after administration of drug ]
    The number of RBC untis transfused per patient during a 48-hour follow-up period after OCTAPLEX administration
  • Use of other blood products [ Time Frame: 48 hours after administration of drug ]
    The use of other blood products during a 48-hour follow-up period after OCTAPLEX administration.
  • Use of haemostatic agents [ Time Frame: 48 hours after administration of drug ]
    The use of haemostatic agents during a 48-hour follow-up period after OCTAPLEX administration.
  • Duration of hospitalisation [ Time Frame: From admission to discharge, approximately 1-3 weeks ]
    Duration of hospitalisation
 
Descriptive Information
Brief Title  ICMJE Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor
Official Title  ICMJE Study of Four-factor Prothrombin Complex Concentrate, OCTAPLEX, in Patients With Acute Major Bleeding on Direct Oral Anticoagulant (DOAC) Therapy With Factor Xa Inhibitor
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Blinded
Primary Purpose: Treatment
Condition  ICMJE Acute Major Bleeding
Intervention  ICMJE Drug: Octaplex
Four-factor prothrombin complex concentrate (4F-PCC)
Study Arms  ICMJE
  • Experimental: Octaplex Low-dose
    Participants to receive 1 Octaplex infusion intravenously
    Intervention: Drug: Octaplex
  • Experimental: Octaplex High-dose
    Participants to receive 1 Octaplex infusion intravenously
    Intervention: Drug: Octaplex
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2024)
260
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2021)
200
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sigurd Knaub, PhD +41554512141 Sigurd.Knaub@octapharma.com
Listed Location Countries  ICMJE Austria,   Bosnia and Herzegovina,   Croatia,   France,   Georgia,   Germany,   Italy,   Poland,   Spain,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04867837
Other Study ID Numbers  ICMJE LEX-210
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Octapharma
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Octapharma
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Octapharma
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP