Clinical trial NCT01623531: Prospective Double Blinded Randomized Control Study of the Use of Fibrinogen in High-Risk Cardiac Surgery
Official title: The Use of Fibrinogen Concentrate in High-Risk Cardiac Surgery. A Prospective, Double-blinded, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Complication During Procedure
Keywords: Fibrinogen
cardiac surgery
high risk
cardiopulmonary bypass
bleeding
blood transfusion
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
First posted: 2012-06-20
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cumulative Transfusion Units
timeFrame: 24 hours after administration of study drug
Secondary outcomes:
measure: Fibrinogen Plasma Concentration (g/L)
timeFrame: 24h after infusion of study drug
measure: Hematocrit (%)
timeFrame: 24h after infusion of study drug
measure: Hemoglobin Concentration (g/L)
timeFrame: 24h after infusion of study drug
measure: Platelet Count (10^3/μL)
timeFrame: 24h after infusion of study drug
measure: Partial Thromboplastin Time (s)
timeFrame: 24h after infusion of study drug
measure: International Normalized Ratio
timeFrame: 24h after infusion of study drug
measure: Prothrombin Time (s)
timeFrame: 24h after infusion of study drug
measure: EXTEM Clotting Time (s)
timeFrame: 24h after infusion of study drug
measure: EXTEM Maximum Clot Firmness (mm)
timeFrame: 24h after infusion of study drug
measure: INTEM Clotting Time (s)
timeFrame: 24h after infusion of study drug
measure: INTEM Maximum Clot Firmness (mm)
timeFrame: 24h after infusion of study drug
measure: FIBTEM Clotting Time (s)
timeFrame: 24h after infusion of study drug
measure: FIBTEM MCF (Maximum Clot Firmness)
timeFrame: 24 hours after study drug administration
measure: HEPTEM Clotting Time (s)
timeFrame: 24h after infusion of study drug
measure: HEPTEM Maximum Clot Firmness (mm)
timeFrame: 24h after infusion of study drug
measure: Total Avoidance of Transfusions
timeFrame: 24h after infusion of study drug
Other outcomes:
measure: Overall Numbers of Patients Receiving Blood Products
timeFrame: 24 hours after administration of study drug
Locations:
city: Halifax
country: Canada
facility: CapitalDHACanada
state: Nova Scotia
Study officials:
affiliation: Nova Scotia Health Authority
name: Myron Kwapisz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.