Deficiency; Fibrinogen, AcquiredPhase 3FIBRESNCT03037424
FIBrinogen REplenishment in Surgery
A Phase 3 study testing Octafibrin and Cryoprecipitate in people with Deficiency; Fibrinogen, Acquired, run by University Health Network, Toronto at 11 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Deficiency; Fibrinogen, Acquired
- What is being tested?
- Octafibrin and Cryoprecipitate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 827 participants
- Where
- 11 sitesCanada
- Study dates
- 22 Feb 2017to 27 Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Canada11 sites
Hamilton Health Science Centre, McMaster University
Hamilton, Ontario, L8S 3Z5
Kingston General Hsopital
Kingston, Ontario, K7L 3N6
London Health Science Centre
London, Ontario, N6A 5A5
Montreal Heart Institute
Montreal, Quebec, H1T 1C8
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
Québec, G1V 4G5
Sunnybrook Health Science Centre
Toronto, Ontario, M4N 3M5
St Michael's Hospital
Toronto, Ontario, M5B 1W8
Tornoto General Hospital, University Health Network
Toronto, Ontario, M5G 2C4
Fraser University Royal Columbia
Vancouver, British Columbia, V3L 3W7
University of Manitoba, St Boniface General Hospital
Winnipeg, Manitoba, R2H 2A6
About this study
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
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
- Being tested
- Octafibrin, Cryoprecipitate
- Keywords
- Cyroprecipitate, Fibrinogen, Cardiac Surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OctafibrinDrug
Octafibrin will be administered when the blood bank receives an order for fibrinogen supplementation
CryoprecipitateDrug
Cryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation
| Study group | Role | What they receive |
|---|---|---|
| Fibrinogen concentrate Octafibrin | Active comparator | Not described Receives: Drug: Octafibrin |
| Cryoprecipitate | Active comparator | Not described Receives: Drug: Cryoprecipitate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2017 (estimated)
- Study start22 Feb 2017
- Primary completion30 Nov 2018
- Study completion27 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Deficiency; Fibrinogen, AcquiredStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 827 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jo Carroll, University Health Network, Toronto
- Investigators
- Keyvan Karkouti, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03037424
- Sponsor's protocol ID
- 16-5636-A
- Acronym
- FIBRES
- Status last verified
- May 2019
- First submitted
- 27 Jan 2017
- Last updated
- 14 May 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37588266Bartoszko 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.
PubMed 35773027Callum 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.
PubMed 31634905Karkouti 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.
PubMed 29678987
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03037424
- Acronym / sponsor ID
- FIBRES / 16-5636-A
- Conditions
- Deficiency; Fibrinogen, Acquired
- Keywords
- Cyroprecipitate, Fibrinogen, Cardiac Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 827 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 22 Feb 2017 (actual)
- Primary completion
- 30 Nov 2018 (actual)
- Study completion
- 27 Mar 2019 (actual)
- First posted
- 31 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fibrinogen concentrate Octafibrin | Active comparator | Drug: Octafibrin |
| Cryoprecipitate | Active comparator | Drug: Cryoprecipitate |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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).
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OctafibrinOctafibrin will be administered when the blood bank receives an order for fibrinogen supplementation | Drug | Fibrinogen concentrate Octafibrin |
| CryoprecipitateCryoprecipitate will be administered when the blood bank receives an order for fibrinogen supplementation | Drug | Cryoprecipitate |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Derived from this study: PubMed 37588266Devine 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.
- Derived from this study: PubMed 35773027Bartoszko 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.
- Derived from this study: PubMed 31634905Callum 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.
- Derived from this study: PubMed 29678987Karkouti 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keyvan Karkouti, MD principal investigator
University Health Network, Toronto
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Octafibrin and Cryoprecipitate in people with Deficiency; Fibrinogen, Acquired, run by University Health Network, Toronto at 11 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03037424, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019; AzTrials last refreshed its copy on 28 Oct 2026.