Clinical trial NCT03037424: FIBrinogen REplenishment in Surgery
Official title: Prospective, Multi-center, Randomized, Active-control, Non-inferiority Study Comparing Fibrinogen Concentrate With Cryoprecipitate for the Treatment of Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deficiency; Fibrinogen, Acquired
Keywords: Cyroprecipitate
Fibrinogen
Cardiac Surgery
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2017-01-31
Enrollment: 827
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pragmatic, prospective, multi-center, randomized, active-control, single-blinded, non-inferiority phase 3 trial in adult cardiac surgical patients. Up to 12 Canadian hospitals will participate, and the trial will require up to 2 years for patient recruitment.

Twelve-hundred bleeding adult cardiac surgical patients who require fibrinogen supplementation due to acquired hypofibrinogenemia after CPB will be included. Patients will be randomized to receive equivalent doses of either fibrinogen concentrate (Octafibrin) or cryoprecipitate when the blood bank receives the first order for fibrinogen supplementation and deems it to be in accordance with accepted clinical standards. Thereafter, patients will be treated according to their assigned group each time fibrinogen supplementation is ordered during the treatment period (24 hours after termination of CPB). No other aspects of care will be modified.

The primary efficacy outcome will be the number of Allogeneic blood products (ABP) (red blood cells \[RBCs\], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB. Safety outcomes will be measured for the first 28 days after surgery, which is the duration of participation of each patient in the trial. Comparisons will be by intention-to-treat (ITT) (primary) and per-protocol (PP) analysis. One interim analysis will be conducted after 600 patients have been treated to determine whether the study should be terminated for safety reasons, demonstrated non-inferiority or futility reasons.


Eligibility criteria: Inclusion Criteria:

1. Patients undergoing index cardiac surgery with CPB in whom fibrinogen supplementation is ordered in accordance with accepted clinical standards (significant hemorrhage and known or presumed hypofibrinogenemia).

Exclusion Criteria:

1. Receipt of fibrinogen rich products (fibrinogen concentrate or cryoprecipitate) within 24 hours before surgery 2. History of severe allergic reaction to cryoprecipitate or fibrinogen concentrate 3. Refusal of ABPs, fibrinogen concentrate or cryoprecipitate due to religious or other reasons 4. Fibrinogen level known to be \>3.0 g/L within 30 minutes of IMP order (to eliminate the risk of raising patients' fibrinogen levels to \>4.0 g/L with supplementation 5. Known pregnancy

Primary outcomes:
measure: The primary endpoint, which is of efficacy, is the comparison of the total number of units of ABPs (RBCs, pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB.
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Fraser University Royal Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba, St Boniface General Hospital
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton Health Science Centre, McMaster University
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hsopital
state: Ontario
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Tornoto General Hospital, University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
Study officials:
affiliation: University Health Network, Toronto
name: Keyvan Karkouti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bartoszko J, Martinez-Perez S, Callum J, Karkouti K; FIBRES Study Investigators. Impact of cardiopulmonary bypass duration on efficacy of fibrinogen replacement with cryoprecipitate compared with fibrinogen concentrate: a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) randomised controlled trial. Br J Anaesth. 2022 Sep;129(3):294-307. doi: 10.1016/j.bja.2022.05.012. Epub 2022 Jun 28.
citation: Callum J, Farkouh ME, Scales DC, Heddle NM, Crowther M, Rao V, Hucke HP, Carroll J, Grewal D, Brar S, Bussieres J, Grocott H, Harle C, Pavenski K, Rochon A, Saha T, Shepherd L, Syed S, Tran D, Wong D, Zeller M, Karkouti K; FIBRES Research Group. Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial. JAMA. 2019 Nov 26;322(20):1966-1976. doi: 10.1001/jama.2019.17312.
citation: Karkouti K, Callum J, Rao V, Heddle N, Farkouh ME, Crowther MA, Scales DC. Protocol for a phase III, non-inferiority, randomised comparison of a new fibrinogen concentrate versus cryoprecipitate for treating acquired hypofibrinogenaemia in bleeding cardiac surgical patients: the FIBRES trial. BMJ Open. 2018 Apr 20;8(4):e020741. doi: 10.1136/bmjopen-2017-020741.