Comparison of Fibrinogen Concentrate and Cryoprecipitate in Pediatric Cardiac Surgery Patients
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- University of Virginia
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- 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
Study Overview
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):
- Cryoprecipitate group (dose: 10 ml/kg; active control group) or
- 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.
Detailed Description
Once the need for fibrinogen supplementation is confirmed, study participants will be randomized into one of two treatment groups (n=15 in each group):
- Cryoprecipitate group (dose: 10 ml/kg; active control group) or
- 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 initially received FC).
Data to be obtained:
- Demographic/preoperative data: collected from the medical record
- age in days/months (all patients to be younger than 24 months)
- gender
- weight
- preoperative diagnosis
- surgery type & date (Norwood, arterial switch, truncus arteriosus, Glenn, Fontan, TAPVR, AV canal, tetralogy of Fallot, etc)
- preoperative standard of care labs PT/aPTT/INR/hgb level/ hematocrit/ platelet count/ fibrinogen level (if exists)/ creatinine
- Intra-operative Data:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- — to 24 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
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).
Intervention: Fibrinogen (Drug)
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).
Intervention: Cryoprecipitate (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Comparison of Post CPB Bleeding (in ml) Between the Study Groups(from administration of fibrinogen concentrate or cryoprecipitate until 48 hours after primary postoperative admission to the ICU)
- Comparison of the Number RBC Units Transfused Immediately After Administration of the Study Medication and Until Postoperative Day 7(From immediately after study medication administration through postoperative day 7)
- Comparison of the Number Platelets Units Transfused Immediately After Administration of the Study Medication and Until Postoperative Day 7(From immediately after study medication administration through postoperative day 7)
- ICU Length of Stay(from admission to the ICU after surgery until 90 days after surgery or discharge from the ICU (whichever occurs earlier))
- Comparison of the Number Plasma Units Transfused Immediately After Administration of the Study Medication and Until Postoperative Day 7(From immediately after study medication administration through postoperative day 7)
- Comparison of Additional Number Cryoprecipitate Units Transfused Immediately After Administration of the Study Medication and Until Postoperative Day 7(From immediately after study medication administration through postoperative day 7)
- Number of Participants With Postoperative Surgical Chest Re-exploration for Excessive Bleeding/Cardiac Tamponade(from admission to the ICU until postoperative day 7)
- Incidence of the Use of Factor VIIa for Bleeding(from separation from CPB until 48 hours after surgery)
- In-hospital Mortality(from admission to the ICU until 30 days after the operation/discharge from the hospital (whichever is earlier))
- Post Operative Acute Kidney Injury (AKI)(from admission to the ICU until postoperative day 7)
- Postoperative Infection(rom admission to the ICU until 30 days after the operation/discharge from the hospital (whichever is earlier))
- Percent of Patients With Postoperative Neurological Injury(from admission to the ICU until POD 7)
- Intubation Time(from admission to the ICU until 30 days after surgery or discharge from the ICU (whichever is earlier))
- Postoperative Thromboembolic Event(from admission to the ICU until 7 days postoperatively)
- Hospital Length of Stay(from admission to the ICU postoperatively until postoperative day 90 or discharge from the hospital (whichever occurs earlier))
Investigators
Jacob Raphael
Professor UVA Department of Anesthesiology
University of Virginia