Fibrinogen Concentrate vs Cryoprecipitate

Repurposing of Fibrinogen Concentrate as a Cost-Effective and Safe Hemostatic Agent in Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass

One of the most common hemostatic derangements in pediatric open- heart surgery is an acute acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet aggregation, resulting in increased bleeding and allogenic blood transfusions.

Currently, fresh frozen plasma and cryoprecipitate are used to supplement fibrinogen in pediatric cardiac patients. We propose that replacing cryoprecipitate with fibrinogen concentrate will be as effective in treating post-CPB bleeding and will decrease total blood product exposure when used as part of a blood transfusion algorithm.

We plan to include all patients undergoing cardiac surgery on CPB less than 12 months and a fibrinogen level <250mg/dL while on bypass.

We hope to demonstrate that fibrinogen concentrate is at least as effective as the standard of care in the management of peri- operative bleeding in neonatal patients undergoing cardiopulmonary bypass. If we are able to demonstrate that fibrinogen is at least as effective as the standard of care, then we would plan a multi-center trial to demonstrate the safety and efficacy of this medication. If we are able to demonstrate that fibrinogen concentrate is effective, fibrinogen concentrate could replace allogenic products and potentially decrease transfusion related morbidity in mortality in this population.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Biological: Cryoprecipitate; Biological: Fibrinogen Concentrate

Detailed Description

Patients under 12 months of age requiring cardiopulmonary bypass surgery will be approached for the study. Patients with a pre- existing coagulopathy, including unexplained bleeding or history of clotting, will be excluded. Prior to the study beginning, patients will be randomized to our standard transfusion algorithm with cryoprecipitate or fibrinogen concentrate. As is standard of care, laboratory tests will be sent at standard times points

1. after the induction of anesthesia,
2. after initiation of bypass,
3. after separation from bypass and administration of protamine, and transfusion of either fibrinogen concentrate or cryoprecipitate
4. on arrival to the ICU. These laboratory tests include hematocrit, arterial blood gas, chemistry, thromboelastogram (TEG) and fibrinogen. Additional laboratory tests will be sent as indicated by the clinical scenario to determine transfusion requirements. For patients enrolled in the study, we will standardize the anesthetic management, cardiopulmonary bypass protocol, and transfusion thresholds in the operating room and ICU. We will collect demographic data, intraop and post-op laboratory values, bypass times, intraop and post op transfusion data, chest tube output, adverse events, and length of ventilation, ICU stay and hospital stay.

For patients randomized to the study arm (fibrinogen concentrate), the fibrinogen level measured on bypass will be used to calculate the appropriate dose of fibrinogen concentrate to achieve a level of 300mg/dL after separation from bypass. Fibrinogen concentrate will replace cryoprecipitate in our post-operative transfusion algorithm. If the patient has continued bleeding based on laboratory values and clinical situation, the patient will be given cryoprecipitate as a rescue measure. Patients not on the study protocol will receive our normal transfusion algorithm.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Georgia
    • Emory, Georgia, United States, 30322
      • Laura Downey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 year (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Neonates of at least 32 weeks of gestational age and infants up to 12 months of age with the diagnosis of congenital heart disease, requiring open heart surgery with cardiopulmonary bypass

Exclusion Criteria:

• Pre-existing coagulopathy, including unexplained bleeding or history of clotting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Cryoprecipitate Arm; Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group	Biological: Cryoprecipitate; Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group
ACTIVE_COMPARATOR: Fibrinogen Concentrate Arm; Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group	Biological: Fibrinogen Concentrate; Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival.	For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets.	From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest Tube Output	Volume of chest tube drainage evaluated over first 24 hours post operatively	From administration end of surgery to 24 hours post operatively
Hours of Mechanical Ventilation		From administration of the drug during surgery to extubation in the ICU (up to 30 days)
Length of Stay in Intensive Care Unit (ICU)		From administration of the drug during surgery to discharge from the ICU (up to 3 months)
Length of Stay in Hospital		From administration of the drug during surgery to discharge from the hospital (up to 6 months)
Count of Participants Who Died Within 30 Days Following Procedure		From administration of the drug to 30 days following surgery

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Emory University
• Investigators: Principal Investigator: Glyn D Williams, MBChB, FFA, Stanford University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2016
• Primary Completion (ACTUAL): April 25, 2018
• Study Completion (ACTUAL): April 25, 2018

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: January 5, 2017
• First Posted (ESTIMATE): January 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2019
• Last Update Submitted That Met QC Criteria: April 14, 2019
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: 36374

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO