FIBrinogen REplenishment in Surgery (FIBRES)

• ClinicalTrials.gov Identifier: NCT03037424
• Recruitment Status: Completed
• First Posted: January 31, 2017
• Last Update Posted: May 14, 2019
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): Jo Carroll, University Health Network, Toronto

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Deficiency; Fibrinogen, Acquired	Drug: Octafibrin; Drug: Cryoprecipitate	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 827 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 22, 2017
• Actual Primary Completion Date: November 30, 2018
• Actual Study Completion Date: March 27, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Fibrinogen concentrate Octafibrin	Drug: Octafibrin; Octafibrin will be administered when the blood bank receives an order for fibrinogen supplementation
Active Comparator: Cryoprecipitate	Drug: Cryoprecipitate; Cryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 24 hours ]
   The number of ABPs (red blood cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Canada, British Columbia

Fraser University Royal Columbia

Vancouver, British Columbia, Canada, V3L 3W7

Canada, Manitoba

University of Manitoba, St Boniface General Hospital

Winnipeg, Manitoba, Canada, R2H 2A6

Canada, Ontario

Hamilton Health Science Centre, McMaster University

Hamilton, Ontario, Canada, L8S 3Z5

Kingston General Hsopital

Kingston, Ontario, Canada, K7L 3N6

London Health Science Centre

London, Ontario, Canada, N6A 5A5

University of Ottawa Heart Institute

Ottawa, Ontario, Canada, K1Y 4W7

Sunnybrook Health Science Centre

Toronto, Ontario, Canada, M4N 3M5

St Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Tornoto General Hospital, University Health Network

Toronto, Ontario, Canada, M5G 2C4

Canada, Quebec

Montreal Heart Institute

Montréal, Quebec, Canada, H1T 1C8

Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval

Quebec, Canada, G1V 4G5

Sponsors and Collaborators

University Health Network, Toronto

Investigators

• Principal Investigator: Keyvan Karkouti, MD; University Health Network, Toronto

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Callum J, Farkouh ME, Scales DC, Heddle NM, Crowther M, Rao V, Hucke HP, Carroll J, Grewal D, Brar S, Bussières 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.

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.

• Responsible Party: Jo Carroll, Manager Anesthesia Research, University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT03037424
• Other Study ID Numbers: 16-5636-A
• First Posted: January 31, 2017
• Last Update Posted: May 14, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jo Carroll, University Health Network, Toronto:

Cyroprecipitate; Fibrinogen; Cardiac Surgery