FIBrinogen REplenishment in Surgery

NCT ID: NCT03037424

Last Updated: 2019-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

827 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-22

Study Completion Date

2019-03-27

Brief Summary

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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.

Detailed Description

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Conditions

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Deficiency; Fibrinogen, Acquired

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Fibrinogen concentrate Octafibrin

Group Type ACTIVE_COMPARATOR

Octafibrin

Intervention Type DRUG

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

Cryoprecipitate

Group Type ACTIVE_COMPARATOR

Cryoprecipitate

Intervention Type DRUG

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

Interventions

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Octafibrin

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

Intervention Type DRUG

Cryoprecipitate

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

Intervention Type DRUG

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Jo Carroll

Manager Anesthesia Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Keyvan Karkouti, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

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Fraser University Royal Columbia

Vancouver, British Columbia, Canada

Site Status

University of Manitoba, St Boniface General Hospital

Winnipeg, Manitoba, Canada

Site Status

Hamilton Health Science Centre, McMaster University

Hamilton, Ontario, Canada

Site Status

Kingston General Hsopital

Kingston, Ontario, Canada

Site Status

London Health Science Centre

London, Ontario, Canada

Site Status

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Site Status

St Michael's Hospital

Toronto, Ontario, Canada

Site Status

Tornoto General Hospital, University Health Network

Toronto, Ontario, Canada

Site Status

Montreal Heart Institute

Montreal, Quebec, Canada

Site Status

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

Québec, , Canada

Site Status

Countries

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Canada

References

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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.

Reference Type DERIVED
PMID: 37588266 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35773027 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31634905 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29678987 (View on PubMed)

Other Identifiers

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16-5636-A

Identifier Type: -

Identifier Source: org_study_id

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