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Comparison of Fibrinogen Concentrate and Cryoprecipitate in Pediatric Cardiac Surgery Patients

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ClinicalTrials.gov Identifier: NCT04376762
Recruitment Status : Not yet recruiting
First Posted : May 6, 2020
Last Update Posted : May 7, 2020
Sponsor:
Collaborator:
Octapharma
Information provided by (Responsible Party):
Jacob Raphael, University of Virginia

Brief Summary:

The aim of the current pilot study proposal is to compare the use of the purified human fibrinogen concentrate (Fibryga®, Octapharma USA) to cryoprecipitate for the treatment of cardiopulmonary bypass (CPB)-associated bleeding in pediatric cardiac patients in whom fibrinogen supplementation is indicated.

The investigators' hypothesis is that fibrinogen concentrate will be as effective as cryoprecipitate in achieving adequate hemostasis after separation from CPB in pediatric cardiac surgery patients.

Study Design: this will be a single-center, prospective, randomized, active-control study in pediatric (24 months of age or younger) patients undergoing elective cardiac surgery with CPB (n=30) in-whom fibrinogen supplementation after separation from CPB is indicated, based on the presence of clinically-significant bleeding and documentation of low fibrinogen level on viscoelastic point-of-care testing (MCF < 10 mm on the FIBTEM assay of ROTEM). Informed consent will be obtained from a parent or a legal guardian prior to surgery and anesthesia. Once the need for fibrinogen supplementation is confirmed, study participants will be randomized into one of two treatment groups (n=15 in each group):

  1. Cryoprecipitate group (dose: 10 ml/kg; active control group) or
  2. Fibrinogen Concentrate group (dose: 70 mg/kg; intervention group). There will be no placebo group since withholding treatment is neither consistent with standard of care nor acceptable ethically. No other aspects of care will be modified. In the event that an additional dose of fibrinogen supplementation is required (bleeding with documented hypofibrinogenemia) cryoprecipitate will be administered to all study subjects (including those who received FC).

The results of this study will be used for publication as well as the first stage towards a significantly larger randomized multi-center trial (see below).

Based on the results of this pilot study the investigators plan to conduct a large multi-center, randomized active-control non-inferiority trial in the future, comparing the use of FC to cryoprecipitate in a much larger cohort of pediatric patients undergoing cardiac surgery with CPB. Ultimately, the results of this trial are likely to improve the care of pediatric cardiac surgical patients experiencing post-CPB bleeding, an under-studied yet high-risk patient population.


Condition or disease Intervention/treatment Phase
Pediatric HD Bleeding Drug: Fibrinogen Drug: Cryoprecipitate Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Fibrinogen Concentrate and Cryoprecipitate in Pediatric Cardiac Surgery Patients
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : August 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Fibrinogen

Arm Intervention/treatment
Experimental: Fibrinogen Concentrate
Fibrinogen Concentrate (dose: 70 mg/kg; intervention group). in-whom fibrinogen supplementation after separation from CPB is indicated, based on the presence of clinically-significant bleeding and documentation of low fibrinogen level on viscoelastic point-of-care testing (MCF < 10 mm on the FIBTEM assay of ROTEM).
Drug: Fibrinogen
Fibrinogen Concentrate (Human) Injection [Fibryga] (dose: 70 mg/kg; intervention group). in-whom fibrinogen supplementation after separation from CPB is indicated, based on the presence of clinically-significant bleeding and documentation of low fibrinogen level on viscoelastic point-of-care testing (MCF < 10 mm on the FIBTEM assay of ROTEM).
Other Name: Fibrinogen Concentrate (Human) Injection [Fibryga]

Active Comparator: Cryoprecipitate
. Cryoprecipitate (dose: 10 ml/kg; active control group) in-whom fibrinogen supplementation after separation from CPB is indicated, based on the presence of clinically-significant bleeding and documentation of low fibrinogen level on viscoelastic point-of-care testing (MCF < 10 mm on the FIBTEM assay of ROTEM).
Drug: Cryoprecipitate
Cryoprecipitate group (dose: 10 ml/kg; active control group) in-whom fibrinogen supplementation after separation from CPB is indicated, based on the presence of clinically-significant bleeding and documentation of low fibrinogen level on viscoelastic point-of-care testing (MCF < 10 mm on the FIBTEM assay of ROTEM).




Primary Outcome Measures :
  1. A composite of the number of any allogeneic blood products (RBCs, plasma, platelets, cryoprecipitate) transfused from administration of the study medication until 48 hours after surgery [ Time Frame: from immediately after the administration of the fibrinogen concentrate or cryoprecipitate through the first 48 hours after admission to the ICU/post anesthesia care unit ]
    comparison between study groups of the number of allogeneic blood products transfused (RBC, plasma, platelets, cryoprecipitate) from immediately after the administration of the study drug (fibrinogen concentrate or cryoprecipitate) until 48 hours since admission to the ICU


Secondary Outcome Measures :
  1. Comparison of post CPB bleeding (in ml) between the study groups [ Time Frame: from administration of fibrinogen concentrate or cryoprecipitate until 48 hours after primary postoperative admission to the ICU ]
    (intraoperatively = cell saver volume in ml; postoperatively = chest drain output in ml)

  2. Comparison of the number RBC units transfused immediately after administration of the study medication and until postoperative day 7 [ Time Frame: From immediately after study medication administration through postoperative day 7 ]
    Comparison between the study groups of the number of RBC units transfused immediately after administration of the study medication (fibrinogen concentrate or cryoprecipitate) until postoperative day 7

  3. Comparison of the number platelets units transfused immediately after administration of the study medication and until postoperative day 7 [ Time Frame: From immediately after study medication administration through postoperative day 7 ]
    Comparison between the study groups of the number of platelets units transfused immediately after administration of the study medication (fibrinogen concentrate or cryoprecipitate) until postoperative day 7

  4. Comparison of the number plasma units transfused immediately after administration of the study medication and until postoperative day 7 [ Time Frame: From immediately after study medication administration through postoperative day 7 ]
    Comparison between the study groups of the number of plasma units transfused immediately after administration of the study medication (fibrinogen concentrate or cryoprecipitate) until postoperative day 7

  5. Comparison of additional number cryoprecipitate units transfused immediately after administration of the study medication and until postoperative day 7 [ Time Frame: From immediately after study medication administration through postoperative day 7 ]
    Comparison between the study groups of the number of additional cryoprecipitate units transfused immediately after administration of the study medication (fibrinogen concentrate or cryoprecipitate) until postoperative day 7

  6. Incidence of postoperative surgical chest re-exploration for excessive bleeding/cardiac tamponade [ Time Frame: from admission to the ICU until postoperative day 7 ]
    Comparison between study groups of the incidence of postoperative surgical chest re-exploration in the ICU/OR for excessive bleeding or cardiac tamponade

  7. Incidence of the use of Factor VIIa for bleeding [ Time Frame: from separation from CPB until 48 hours after surgery ]
    comparison of percent of patients requiring factor VIIa for bleeding (intraoperatively or postoperatively in the ICU between the study groups

  8. In-hospital mortality [ Time Frame: from admission to the ICU until 30 days after the operation/discharge from the hospital (whichever is earlier) ]
    comparison of the incidence of in-hospital mortality between the study groups

  9. Post operative Acute Kidney injury (AKI) [ Time Frame: from admission to the ICU until postoperative day 7 ]
    comparison of the incidence of postoperative AKI between study groups. AKI will be assessed based on the Acute Kidney Injury Network (AKIN) classification (stages 0-3, with higher stage reflecting worse outcome)

  10. Postoperative infection [ Time Frame: rom admission to the ICU until 30 days after the operation/discharge from the hospital (whichever is earlier) ]
    comparison of the incidence of pneumonia, sternal wound infection, mediastinitis, sepsis between study groups

  11. percent of patients with postoperative neurological injury [ Time Frame: from admission to the ICU until POD 7 ]
    Comparison between study groups of the percent of patients with seizures/stroke that occur after surgery

  12. Intubation time [ Time Frame: from admission to the ICU until 30 days after surgery or discharge from the ICU (whichever is earlier) ]
    comparison of the time to extubation from the completion of surgery until extubation in the ICU between the study groups

  13. postoperative thromboembolic event [ Time Frame: from admission to the ICU until 7 days postoperatively ]
    comparison of the incidence of DVT/PE/shunt thrombosis between the study groups

  14. ICU length of stay [ Time Frame: from admission to the ICU after surgery until 90 days after surgery or discharge from the ICU (whichever occurs earlier) ]
    comparison of the postoperative time period spent in the ICU

  15. Hospital length of stay [ Time Frame: from admission to the ICU postoperatively until postoperative day 90 or discharge from the hospital (whichever occurs earlier) ]
    comparison between the study groups of the time in the hospital from admission to the ICU postoperatively until discharge from the hospital


Other Outcome Measures:
  1. Percent of patients requiring postoperative Extra Corporeal Membrane Oxygenation (ECMO) support [ Time Frame: from separation from CPB until postoperative day 30 (or discharge from the hospital (whichever occurs earlier) ]
    comparison between the groups of the incidence of the need for postoperative circulatory support with ECMO



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.


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Ages Eligible for Study:   up to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • pediatric (age 24 months or younger) patients undergoing elective cardiac surgery with CPB (n=30) in-whom fibrinogen supplementation after separation from CPB is indicated, based on the presence of clinically-significant bleeding and documentation of low fibrinogen level on viscoelastic point-of-care testing (MCF < 10 mm on the FIBTEM assay of ROTEM).

Exclusion Criteria:

  • gestational age < 33 weeks at birth
  • gestational age < 35 weeks on the day of surgery
  • emergency surgery
  • patient or parent history of coagulopathy/clotting abnormalities
  • patient history of thrombophilia
  • refusal to participate in the study,
  • known severe allergic reaction/anaphylaxis to fibrinogen concentrate,
  • administration of fibrinogen concentrate or cryoprecipitate in the 24 hours prior to surgery
  • baseline fibrinogen level higher than 300 mg/dL (to avoid the risk of increasing the fibrinogen level above the normal upper level of 400 mg/dL)

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): NCT04376762


Contacts
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Contact: Marcia Birk, RN 434-924-2283 meb2w@virginia.edu

Locations
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United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Octapharma
Investigators
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Principal Investigator: Jacob Raphael, MD UVA Anesthesiology
Publications:

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Responsible Party: Jacob Raphael, Professor UVA Department of Anesthesiology, University of Virginia
ClinicalTrials.gov Identifier: NCT04376762    
Other Study ID Numbers: HSR180028-FC vs Cryo
First Posted: May 6, 2020    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Hemorrhage
Pathologic Processes