Comparison of Fibrinogen Concentrate and Cryoprecipitate in Pediatric Cardiac Surgery Patients

NCT04376762 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HSR180028-FC vs Cryo
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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. 1.Cryoprecipitate group (dose: 10 ml/kg; active control group) or
2. 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).

Conditions

Pediatric HD; Bleeding

Outcome Measures

Primary Outcomes (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

  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

  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

Secondary Outcomes (15)

• 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

• 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

Study Arms (2)

Fibrinogen Concentrate

EXPERIMENTAL

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

Cryoprecipitate

ACTIVE COMPARATOR

. 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

Interventions

Fibrinogen DRUG

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).

Also known as: Fibrinogen Concentrate (Human) Injection [Fibryga]

Fibrinogen Concentrate

Cryoprecipitate DRUG

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).

Cryoprecipitate

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Virginia: lead
• Octapharma: collaborator

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (6)

• Hvas AM, Andreasen JB, Christiansen K, Ravn HB. Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery. Blood Coagul Fibrinolysis. 2013 Sep;24(6):587-92. doi: 10.1097/MBC.0b013e32836029d2.

  PMID: 23571685 BACKGROUND

• Galas FR, de Almeida JP, Fukushima JT, Vincent JL, Osawa EA, Zeferino S, Camara L, Guimaraes VA, Jatene MB, Hajjar LA. Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: a randomized pilot trial. J Thorac Cardiovasc Surg. 2014 Oct;148(4):1647-55. doi: 10.1016/j.jtcvs.2014.04.029. Epub 2014 Apr 18.

  PMID: 24951020 BACKGROUND

• Haas T, Spielmann N, Restin T, Seifert B, Henze G, Obwegeser J, Min K, Jeszenszky D, Weiss M, Schmugge M. Higher fibrinogen concentrations for reduction of transfusion requirements during major paediatric surgery: A prospective randomised controlled trial. Br J Anaesth. 2015 Aug;115(2):234-43. doi: 10.1093/bja/aev136. Epub 2015 May 15.

  PMID: 25982134 BACKGROUND

• Haas T, Cushing MM, Asmis LM. Comparison of the efficacy of two human fibrinogen concentrates to treat dilutional coagulopathy in vitro. Scand J Clin Lab Invest. 2018 May;78(3):230-235. doi: 10.1080/00365513.2018.1437645. Epub 2018 Feb 15.

  PMID: 29446989 BACKGROUND

• Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A; Surgical Clinical Outcome REsearch (SCORE) Group. Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc. 2015 Jun 2;4(6):e002066. doi: 10.1161/JAHA.115.002066.

  PMID: 26037084 BACKGROUND

• Fassl J, Lurati Buse G, Filipovic M, Reuthebuch O, Hampl K, Seeberger MD, Bolliger D. Perioperative administration of fibrinogen does not increase adverse cardiac and thromboembolic events after cardiac surgery. Br J Anaesth. 2015 Feb;114(2):225-34. doi: 10.1093/bja/aeu364. Epub 2014 Oct 16.

  PMID: 25324348 BACKGROUND

MeSH Terms

Conditions

Hemorrhage

Interventions

Fibrinogen; Injections; cryoprecipitate coagulum

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Jacob Raphael
• Organization: Thomas Jefferson University

jacob.raphael@jefferson.edu

215-955-6161

Study Officials

• Keita Ikeda, MD

  UVA Anesthesiology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor UVA Department of Anesthesiology

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: May 6, 2020
• Study Start: October 26, 2021
• Primary Completion: March 1, 2023
• Study Completion: May 1, 2023
• Last Updated: March 6, 2026
• Results First Posted: March 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)