NCT03037424: FIBRES

FIBrinogen REplenishment in Surgery

Completed Phase 3 Last updated 14 May 2019

What this trial tests

Phase 3 trial testing Octafibrin in Deficiency; Fibrinogen, Acquired in 827 participants. Completed in 27 March 2019.

Timeline

22 February 2017

Primary endpoint
30 November 2018

27 March 2019

Quick facts

Lead sponsor	University Health Network, Toronto
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	827
Start date	22 February 2017
Primary completion	30 November 2018
Estimated completion	27 March 2019
Sites	11 locations across Canada

Drugs / interventions tested

• Octafibrin — full drug profile →
• Cryoprecipitate — full drug profile →

Conditions studied

• Deficiency; Fibrinogen, Acquired — all drugs for Deficiency; Fibrinogen, Acquired →

Sponsor

University Health Network, Toronto

Who can join

Eligibility, any sex, with Deficiency; Fibrinogen, Acquired. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial.
   Callum J, Farkouh ME, Scales DC, Heddle NM, et al · · 2019 · cited 123× · PMID 31634905 · DOI 10.1001/jama.2019.17312
2. Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients.
   Abrahamyan L, Tomlinson G, Callum J, Carcone S, et al · · 2023 · cited 17× · PMID 36598773 · DOI 10.1001/jamasurg.2022.6818
3. 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.
   Karkouti K, Callum J, Rao V, Heddle N, et al · · 2018 · cited 15× · PMID 29678987 · DOI 10.1136/bmjopen-2017-020741
4. Pro-coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia.
   Fabes J, Brunskill SJ, Curry N, Doree C, et al · · 2018 · cited 11× · PMID 30582172 · DOI 10.1002/14651858.cd010649.pub2
5. 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.
   Bartoszko J, Martinez-Perez S, Callum J, Karkouti K, et al · · 2022 · cited 10× · PMID 35773027 · DOI 10.1016/j.bja.2022.05.012
6. Weight-adjusted dosing of fibrinogen concentrate and cryoprecipitate in the treatment of hypofibrinogenaemic bleeding adult cardiac surgical patients: a <i>post hoc</i> analysis of the Fibrinogen Replenishment in cardiac surgery randomised controlled trial.
   Devine C, Bartoszko J, Callum J, Karkouti K, et al · · 2022 · PMID 37588266 · DOI 10.1016/j.bjao.2022.100016