This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (FARES-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05523297
Recruitment Status : Recruiting
First Posted : August 31, 2022
Last Update Posted : January 9, 2024
Sponsor:
Information provided by (Responsible Party):
Octapharma

Brief Summary:
This is a multicentre, active-control randomized, prospective, Phase 3 study in adult cardiac surgery patients. Approximately 500 patients will be randomized at approximately 12 hospitals.

Condition or disease Intervention/treatment Phase
Bleeding Cardiac Surgery Patients Drug: Octaplex Drug: Frozen Plasma Product, Human Phase 3

Detailed Description:

Patients will be randomized to receive either 4-factor PCC (Octaplex) or frozen plasma (FP).

The study will compare the hemostatic treatment response to Octaplex versus FP, defined as effective if no additional systemic or surgical hemostatic intervention is required from 60 minutes to 24 hours after initiation of the first treatment dose.

The study will include adult (≥18 years old) patients who undergo cardiac surgery with cardiopulmonary bypass (CPB) and require coagulation factor replacement due to bleeding post-CPB and after adequate reversal of heparin with protamine (as assessed by the surgical staff based on clinical and laboratory criteria) during surgery, and who have a known (e.g., as indicated by INR) or suspected coagulation factor deficiency.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Masking Description: Given the physical differences in the products and the emergency nature of the intervention, attending clinicians present during the infusion of the blood products/components will not be blinded to the treatment. To minimize bias, treating clinicians will be blinded to group assignments until immediately prior to IMP infusion.
Primary Purpose: Treatment
Official Title: Prospective, Multicentre, Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Bleeding Adult Cardiac Surgical Patients
Actual Study Start Date : November 10, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Octaplex
Each participant to receive up to 2 Octaplex infusion intravenously within first 24 hours. Exceeding 24 hours frozen plasma will be administered
Drug: Octaplex
Prothrombin complex concentrate

Active Comparator: Frozen plasma
Each participant will be administered FP according to the local standard
Drug: Frozen Plasma Product, Human
If additional treatment is required after the maximum dose of IMP is administered or the treatment period has elapsed, patients in both groups will receive frozen plasma




Primary Outcome Measures :
  1. Number of patients requiring additional hemostatic intervention [ Time Frame: 60 minutes to 24 hours after first dose of IMP ]
    Defined as 'effective' if no additional hemostatic intervention, such as administration of any systemic hemostatic agents (including platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII, other coagulation factor products or a second dose of IMP) or any hemostatic interventions (including surgical re-opening for bleeding) is required from 60 minutes to 24 hours after initiation of the first dose of IMP.


Secondary Outcome Measures :
  1. Number of patients requiring additional hemostatic intervention based on hemoglobin level [ Time Frame: 60 minutes to 24 hours after first dose of IMP ]
    Defined as 'positive' if no additional hemostatic intervention is required and hemoglobin levels decrease by <30% (after accounting for red cell transfusions) from 60 minutes to 24 hours after initiation of the first dose of IMP.

  2. Compare the amount of chest tube drainage between the Octaplex and FP groups. [ Time Frame: 12 and 24 hours after chest closure ]
  3. Compare the incidence of severe to massive bleeding between the Octaplex and FP groups using a modification of the universal definition of perioperative bleeding (UDPB). [ Time Frame: 24 hours after surgery start, after the end of CPB and after IMP initiation ]
  4. Compare efficacy in terms of the mean number of total allogeneic blood components (IMP and non-IMP) transfused between the Octaplex and FP groups. [ Time Frame: 24 hours after the end of CPB and after IMP initiation ]
  5. Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups. [ Time Frame: 24 hours after the end of CPB and after IMP initiation ]
  6. Compare efficacy in terms of the mean number of total non-IMP allogeneic blood components transfused between the Octaplex and FP groups. [ Time Frame: 24 hours and 7 days after the end of CPB and after IMP initiation ]
  7. Compare mean number of individual allogeneic blood components transfused between the Octaplex and FP groups. [ Time Frame: 24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation ]
  8. Compare efficacy in terms of the incidence of transfusion of individual allogeneic blood components transfused between the Octaplex and FP groups. [ Time Frame: 24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation ]
  9. Compare incidence of administration of non-IMP coagulation factor products between Octaplex and FP groups [ Time Frame: 24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation ]
  10. Compare incidence of intracerebral hemorrhage between the Octaplex and FP groups [ Time Frame: 24 hours after start of surgery, after the end of CPB and after IMP initiation ]
  11. Compare incidence of gastrointestinal hemorrhage between Octaplex and FP groups [ Time Frame: 24 hours after start of surgery, after the end of CPB and after IMP initiation ]
  12. Compare incidence of surgical re-exploration between Octaplex and FP groups [ Time Frame: 24 hours after start of surgery, after the end of CPB and after IMP initiation ]
  13. Compare the effect of Octaplex versus FP administration on the change in international normalised ratio (INR) before and after therapy administration. [ Time Frame: Within 30 minutes before to within 60 minutes after the initiation of IMP administration. ]
    INR reduction will be considered successful if the magnitude of the reduction is >1.0 or the post-treatment level drops below 1.5

  14. Compare the effect of Octaplex versus FP administration on Prothrombin Time (PT) [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  15. Compare the effect of Octaplex versus FP administration on aPTT [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  16. Compare the effect of Octaplex versus FP administration on fibrinogen activity [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  17. Compare the effect of Octaplex versus FP administration on ROTEM EXTEM CT [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  18. Compare the effect of Octaplex versus FP administration on ROTEM EXTEM MCT [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  19. Compare the effect of Octaplex versus FP administration on ROTEM FIBTEM MCF [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  20. Compare the effect of Octaplex versus FP administration on platelets [ Time Frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration ]
  21. Compare total time elapsed from initiation of the first dose of IMP to arrival at the ICU room between the Octaplex and FP groups. [ Time Frame: From initiation of IMP to arrival at ICU room (within 24 hours) ]
  22. Comparison of incidence of serious treatment-emergent adverse events between Octaplex and FP groups [ Time Frame: From start of IMP administration up to 30 days post-operatively ]
  23. Comparison of the duration of mechanical ventilation between Octaplex and FP groups [ Time Frame: From start of IMP administration up to 30 days post-operatively ]
  24. Comparison of the duration of ICU stay between Octaplex and FP groups [ Time Frame: From start of IMP administration up to 30 days post-operatively ]
  25. Comparison of the duration of hospitalization between Octaplex and FP groups [ Time Frame: From start of IMP administration up to 30 days post-operatively ]
  26. Comparison of the incidence of death between Octaplex and FP groups [ Time Frame: From start of IMP administration up to 30 days post-operatively ]
  27. Comparison of the number of days alive and out of hospital between Octaplex and FP groups [ Time Frame: From start of IMP administration up to 30 days post-operatively ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult (≥18 years old) patients undergoing any index cardiac surgery employing CPB
  2. Coagulation factor replacement with PCC or FP ordered in the operating room for:

    1. Management of bleeding, or
    2. Anticipated bleeding in a patient who has been on-pump for >2 hours or has undergone a complex procedure (e.g., aortocoronary bypass [ACB] plus aortic valve replacement)
  3. Coagulation factor deficiency, either known to exist (e.g., as indicated by elevated EXTEM clotting time [CT] or INR) or suspected based on the clinical situation
  4. Patients who have given written informed consent. In United States patients will provide informed consent prior to surgery. In Canada, informed consent will be obtained after surgery, in accordance with Article 3.7A of the 2018 Tri- Council Policy Statement on the Ethical Conduct for Research Involving Humans.

Exclusion Criteria:

  1. Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump [IABP]) or repair of thoracoabdominal aneurysm
  2. Critical state immediately before surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before surgery)
  3. Severe right heart failure (clinical diagnosis ± echocardiography)
  4. Known contraindications to heparin
  5. PCC required for reversal of warfarin or direct oral anticoagulant (DOAC; dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to or during surgery
  6. Known thromboembolic event (TEE) within 3 months prior to surgery
  7. History of severe allergic reactions to PCC or FP
  8. Individuals who have immunoglobulin A (IgA) deficiency with known antibodies against IgA
  9. Refusal of allogeneic blood products
  10. Known pregnancy
  11. Currently enrolled in other interventional clinical trials

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05523297


Contacts
Layout table for location contacts
Contact: Sigurd Knaub +41795330529 Sigurd.Knaub@Octapharma.com

Locations
Layout table for location information
United States, North Carolina
Duke University Health System Recruiting
Durham, North Carolina, United States, 27710
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Canada, British Columbia
Royal Columbian Hospital Recruiting
New Westminster, British Columbia, Canada, V3L 3W7
University of British Columbia and Vancouver Coastal Health Authority Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Hamilton Health Sciences Corporation Recruiting
Hamilton, Ontario, Canada, L8L 8E7
Kingston General Hospital Recruiting
Kingston, Ontario, Canada, K7L 2V7
London Health Sciences Recruiting
London, Ontario, Canada, N6A 5A5
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Sunnybrook Hospital Recruiting
Toronto, Ontario, Canada, M4N 3M5
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada, M5B 1W8
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
Montreal Heart Institute Recruiting
Montréal, Quebec, Canada, H1T 1C8
Quebec Laval Recruiting
Québec, Quebec, Canada, G1V 4G5
Sponsors and Collaborators
Octapharma
Layout table for additonal information
Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT05523297    
Other Study ID Numbers: LEX-211
First Posted: August 31, 2022    Key Record Dates
Last Update Posted: January 9, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hemorrhage
Pathologic Processes