Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01623531
Other study ID # Fibrinogenstudy0911
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date February 2014
Est. completion date June 30, 2019

Study information

Verified date May 2020
Source Nova Scotia Health Authority
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 (ROTEMĀ®, 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.


Recruitment information / eligibility

Status Completed
Enrollment 62
Est. completion date June 30, 2019
Est. primary completion date March 31, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms

  • Cardiac Complication During Procedure

Intervention

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

Locations

Country Name City State
Canada CapitalDHACanada Halifax Nova Scotia

Sponsors (1)

Lead Sponsor Collaborator
Nova Scotia Health Authority

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Overall Numbers of Patients Receiving Blood Products Including Packed Red Cells, Fresh Frozen Plasma, Platelets, Cryoprecipitate and coagulation factor concentrates. The study was not sufficiently powered to test differences between this outcome. 24 hours after administration of study drug
Primary Cumulative Transfusion Units Including packed red cells, frozen plasma, platelets, cryoprecipitates 24 hours after administration of study drug
Secondary Fibrinogen Plasma Concentration (g/L) 24h after infusion of study drug
Secondary Hematocrit (%) 24h after infusion of study drug
Secondary Hemoglobin Concentration (g/L) 24h after infusion of study drug
Secondary Platelet Count (10^3/µL) 24h after infusion of study drug
Secondary Partial Thromboplastin Time (s) 24h after infusion of study drug
Secondary International Normalized Ratio International normalized ratio (INR) is calculated based on the prothrombin time (PT) test results.The PT is usually measured in seconds and is compared to a normal range that reflects PT values in healthy individuals. Because the reagents used to perform the PT test vary from one laboratory to another and even within the same laboratory over time, the normal ranges also will fluctuate. To standardize results across different laboratories in the world, a World Health Organization (WHO) committee developed and recommended the use of the Internationalized Normalized Ratio (INR). The INR is calculated with the ratio of the patient's prothrombin time (PT test) to a normal prothrombin time (control) sample (PT normal): INR=PT test:PT normal. The normal range is from 0.9 to 1.2. The higher the value the more is the patient anticoagulated. This means the patient's blood is thinner with a lower concentration of coagulation factors. 24h after infusion of study drug
Secondary Prothrombin Time (s) The prothrombin time (PT) test evaluates how well all of the coagulation factors in the extrinsic and common pathways of the coagulation cascade work together. Included are: factors I (Fibrinogen), II (Prothrombin), V, VII and X. 24h after infusion of study drug
Secondary EXTEM Clotting Time (s) EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). 24h after infusion of study drug
Secondary EXTEM Maximum Clot Firmness (mm) EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII. 24h after infusion of study drug
Secondary INTEM Clotting Time (s) INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). 24h after infusion of study drug
Secondary INTEM Maximum Clot Firmness (mm) INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII. 24h after infusion of study drug
Secondary FIBTEM Clotting Time (s) FIBTEM = rotational thrombelastometry (measurement of functional fibrinogen); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). 24h after infusion of study drug
Secondary FIBTEM MCF (Maximum Clot Firmness) Rotational thrombelastometry (measurement of functional fibrinogen). Rotational thrombelastometry (ROTEM) is a point-of-care viscoelastic coagulation test. The device provides four channels for simultaneous assays. With the so called "FIBTEM" assay coagulation is activated by a small amount of tissue thromboplastin (tissue factor) and platelets are blocked with cytochalasin D. The resulting clot is therefore only depending on fibrin formation and fibrin polymerisation. The maximum clot firmness (MCF) is the amplitude in mm on the result graph representing the increasing stabilisation of the clot. 24 hours after study drug administration
Secondary HEPTEM Clotting Time (s) HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase);clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). 24h after infusion of study drug
Secondary HEPTEM Maximum Clot Firmness (mm) HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII. 24h after infusion of study drug
Secondary Total Avoidance of Transfusions Total avoidance of any transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo. 24h after infusion of study drug