Prospective Double Blinded Randomized Control Study of the Use of Fibrinogen in High-Risk Cardiac Surgery

NCT ID: NCT01623531

Last Updated: 2020-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2019-06-30

Brief Summary

The aim of the study is to show that first line treatment with concentrated fibrinogen has superiority over the conventional therapy with fresh frozen plasma (FFP), platelets, and cryoprecipitate in perioperative management of bleeding after complex cardiac surgery.

Detailed Description

All patients will be recruited from the Queen Elizabeth II (QEII) Health Sciences Center, Halifax, Nova Scotia, which is the sole tertiary cardiac surgical referral center in Nova Scotia that performs approximately 1000 open heart surgical procedures yearly, including more than 700 isolated coronary artery bypass graft (CABG) procedures.

Inclusion criteria: All patients who are scheduled for elective complex cardiac surgical procedures including, double procedures (aortic valve replacement+coronary artery bypass graft , mitral valve replacement+coronary artery bypass graft , aortic valve replacement+mitral valve replacement), redo-sternotomies, and aortic root repair +/-aortic valve replacement.

Exclusion criteria: Any known congenital or preexisting bleeding disorder, preexisting clinically significant abnormal fibrinogen level, severe liver disease (alanine aminotransferase or aspartate aminotransferase > 150 U/l), inability of providing informed consent, emergency surgery, pregnancy or nursing, age under 18 years, intake of anti-platelet drugs within the last 2- 5 days before surgery (low dose aspirin is allowed) allergy to concentrated fibrinogen or other components in the product, anemia (Hb < 110), diagnosed deep venous thrombosis, pulmonary embolism, acute stroke or acute myocardial infarction.

The primary outcome: Cumulative perioperative amount (number of units and total volume) of blood components used between the start of surgery and 24 hours after administration of the study drug or placebo. 'Blood Components' are defined as all fresh components of blood (RBCs, plasma, platelets, and Cryo).

The secondary outcomes: Fibrinogen levels, hematocrit, prothrombin time (PT), partial prothrombin time (PTT), INR, platelet count, Hemoglobin (Hb), Thromboelastometry (ROTEM®, clotting time (CT), clot formation time (CFT), Angle, maximum clot firmness (MCF), Cardiovascular intensive care unit (CVICU-stay), Hospital-stay, In-Hospital Mortality, Hemoglobin, adverse events (anaphylaxis, stroke, myocardial infarction, pulmonary embolism, and deep vein thromboembolism) and usage of factor VII concentrate and human prothrombin complex (factors II, VII,IX, X), total avoidance of transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo.

Conditions

Cardiac Complication During Procedure

Study Design

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

Study Groups

RiaSTAP

Intravenous fibrinogen(RiaSTAP) will be administered according to FIBTEM based calculation formula

Group Type: ACTIVE_COMPARATOR

Fibrinogen

Intervention Type: DRUG

Intravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM)

Intravenous saline

Intravenous saline (placebo) will be calculated according to FIBTEM based calculation formula

Group Type: PLACEBO_COMPARATOR

Fibrinogen

Intervention Type: DRUG

Intravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM)

Interventions

Fibrinogen

Intravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM)

Intervention Type: DRUG

Other Intervention Names

RiaSTAP or Haemocomplettan P

Eligibility Criteria

Inclusion Criteria

All patients who are scheduled for elective complex cardiac surgical procedures including

• double procedures (aortic valve replacement (AVR)+CABG, mitral valve repair/replacement (MVR)+CABG, AVR+MVR)
• Redo-sternotomies
• Aortic root repair +/- AVR

Exclusion Criteria

• Any known congenital or pre-existing bleeding disorder
• pre-existing clinically significant abnormal fibrinogen level (normal: 2.5-4.79g/l)
• severe liver disease (alanine aminotransferase or aspartate aminotransferase > 150 U/l)
• inability to provide informed consent
• emergency surgery
• pregnancy or nursing
• age under 18 years
• intake of anti-platelet drugs within2- 5 days preoperatively (low dose ASA is allowed)
• allergy to concentrated fibrinogen or other components in the product
• anemia (Hgb < 110)
• diagnosed deep vein thrombosis (DVT)
• pulmonary embolism
• acute stroke
• acute myocardial infarction

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nova Scotia Health Authority

OTHER

Sponsor Role: lead

Responsible Party

Myron Kwapisz, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Myron Kwapisz, MD

Role: PRINCIPAL_INVESTIGATOR

Nova Scotia Health Authority

Locations

CapitalDHACanada

Halifax, Nova Scotia, Canada

Countries

Canada

References

Kwapisz MM, Kent B, DiQuinzio C, LeGare JF, Garnett S, Swyer W, Whynot S, Mingo H, Scheffler M. The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery. Acta Anaesthesiol Scand. 2020 May;64(5):602-612. doi: 10.1111/aas.13540. Epub 2020 Jan 17.

Reference Type: BACKGROUND

PMID: 31889306 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Fibrinogenstudy0911

Identifier Type: -

Identifier Source: org_study_id