FIBrinogen REplenishment in Surgery

NCT03037424 | Completed Phase 3

• 1 other identifier: 16-5636-A
• Study Type: interventional
• Target: 827
• Locations: 1 country
• Sites: 11

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.

Conditions

Deficiency; Fibrinogen, Acquired

Keywords

Cyroprecipitate; Fibrinogen; Cardiac Surgery

Outcome Measures

Primary Outcomes (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.

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

  24 hours

Study Arms (2)

Fibrinogen concentrate Octafibrin

ACTIVE COMPARATOR

Drug: Octafibrin

Cryoprecipitate

ACTIVE COMPARATOR

Drug: Cryoprecipitate

Interventions

Octafibrin DRUG

Octafibrin will be administered when the blood bank receives an order for fibrinogen supplementation

Fibrinogen concentrate Octafibrin

Cryoprecipitate DRUG

Cryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation

Cryoprecipitate

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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).

You may not qualify if:

• \. 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (11)

Fraser University Royal Columbia

Vancouver, British Columbia, V3L 3W7, Canada

Location

University of Manitoba, St Boniface General Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Hamilton Health Science Centre, McMaster University

Hamilton, Ontario, L8S 3Z5, Canada

Location

Kingston General Hsopital

Kingston, Ontario, K7L 3N6, Canada

Location

London Health Science Centre

London, Ontario, N6A 5A5, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Tornoto General Hospital, University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

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

Québec, G1V 4G5, Canada

Location

Related Publications (4)

• Devine C, Bartoszko J, Callum J, Karkouti K; FIBRES Study Investigators. Weight-adjusted dosing of fibrinogen concentrate and cryoprecipitate in the treatment of hypofibrinogenaemic bleeding adult cardiac surgical patients: a post hoc analysis of the Fibrinogen Replenishment in cardiac surgery randomised controlled trial. BJA Open. 2022 Jun 9;2:100016. doi: 10.1016/j.bjao.2022.100016. eCollection 2022 Jun.

  PMID: 37588266 DERIVED

• 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.

  PMID: 35773027 DERIVED

• 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.

  PMID: 31634905 DERIVED

• 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.

  PMID: 29678987 DERIVED

MeSH Terms

Interventions

cryoprecipitate coagulum

Study Officials

• Keyvan Karkouti, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Manager Anesthesia Research

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: January 31, 2017
• Study Start: February 22, 2017
• Primary Completion: November 30, 2018
• Study Completion: March 27, 2019
• Last Updated: May 14, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)