Fibrinogen Concentrate vs Cryoprecipitate

NCT ID: NCT03014700

Last Updated: 2019-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-04-25

Brief Summary

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.

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.

Conditions

Congenital Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Cryoprecipitate Arm

Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group

Group Type: ACTIVE_COMPARATOR

Cryoprecipitate

Intervention Type: BIOLOGICAL

Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group

Fibrinogen Concentrate Arm

Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group

Group Type: ACTIVE_COMPARATOR

Fibrinogen Concentrate

Intervention Type: BIOLOGICAL

Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group

Interventions

Fibrinogen Concentrate

Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group

Intervention Type: BIOLOGICAL

Cryoprecipitate

Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Glyn David Williams

Professor, Department of Anesthesiology, Perioperative and Pain Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Glyn D Williams, MBChB, FFA

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Laura Downey, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Stanford University Medical Center

Stanford, California, United States

Laura Downey

Emory, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

36374

Identifier Type: -

Identifier Source: org_study_id