Bleeding in Cardiac SurgeryPhase 2FARESNCT04114643
Factor Replacement in Surgery
A Phase 2 study testing Prothrombin Complex Concentrate and Frozen Plasma in people with Bleeding in Cardiac Surgery, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This is a multicentre, randomized, active-control, pragmatic, Phase 2 pilot study in adult cardiac surgery patients. Two Canadian hospitals will participate, and it is estimated that the study will take approximately 9 months to complete. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bleeding in Cardiac Surgery
- What is being tested?
- Prothrombin Complex Concentrate and Frozen Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteCanada
- Study dates
- 24 Sep 2019to 31 Dec 2020
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing any index cardiac surgery with or without CPB in whom coagulation factor replacement with PCC or FP is ordered in the operating room for:
- Management of bleeding, or
- Anticipated bleeding in a patient who has
- been on-pump for >2 hours, or
- undergone a complex procedure (e.g., ACB + AVR). Coagulation factor deficiency must either be known to exist (as indicated by elevated EXTEM clotting time [CT] or international normalized ratio [INR]), or be suspected based on the clinical situation.
Who cannot join
- Patients who meet any of the following criteria are not eligible for the study:
- Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump [IABP]), or repair of thoracoabdominal aneurysm
- Critical state immediately before emergency surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before start of surgery)
- History of heparin induced thrombocytopenia
- Last preoperative INR >1.5 and patient on warfarin
- Taken dabigatran, rivaroxaban, apixaban, or edoxaban within 48 hours of start of surgery
Show all 10Show fewer
- Administered PCC or FP within 48 hours before start of surgery
- History of severe allergic reaction to PCC or FP
- Refusal of allogeneic blood products due to religious or other reasons
- Known pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prothrombin Complex Concentrate Versus Frozen Plasma in Bleeding Adult Cardiac Surgical Patients: A Multicentre, Randomized, Active-control, Pragmatic, Phase 2 Pilot Study
This is a multicentre, randomized, active-control, pragmatic, Phase 2 pilot study in adult cardiac surgery patients. Two Canadian hospitals will participate, and it is estimated that the study will take approximately 9 months to complete.
Approximately 120 bleeding adult cardiac surgical patients who require coagulation factor replacement during cardiac surgery will be included. Patients will be randomized to receive either PCC or FP when the blood bank receives the first order for coagulation factor replacement and deems it to be in accordance with accepted clinical standards. Patients will be treated according to their assigned group on the first and second times when coagulation factor replacement is ordered during the treatment period (24 hours after randomization). For any additional doses (i.e., the third dose and thereafter), patients in both groups will receive FP (in 1U increments at the discretion of the ordering physician). No other aspects of care will be modified.
This pilot study aims to select a clinically relevant primary efficacy endpoint for a confirmative Phase 3 study, which will subsequently aim to determine if PCC is non-inferior or superior to FP in terms of effica-cy and safety in bleeding cardiac surgical patients. In the pilot study, safety outcomes will be measured for the first 28 days, which is the duration of participation of each patient in the trial.
- Conditions
- Bleeding in Cardiac Surgery
- Being tested
- Prothrombin Complex Concentrate, Frozen Plasma
- Keywords
- Frozen Plasma (FP), Prothrombin Complex Concentrate (PCC), Octaplex, Coagulation Factor Replacement, Transfusion, Bleeding Cardiac Surgical Patients, Pilot, Phase 2
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prothrombin Complex ConcentrateBiological
Also called Octaplex
Octaplex will be administered when the blood bank receives an order for coagulation factor replacement
Frozen PlasmaBiological
Also called Fresh Frozen Plasma
Frozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement
| Study group | Role | What they receive |
|---|---|---|
| Prothrombin Complex Concentrate | Active comparator | Not described Receives: Biological: Prothrombin Complex Concentrate |
| Frozen Plasma | Active comparator | Not described Receives: Biological: Frozen Plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment response
Administration of hemostatic agents including a second dose of IMP, platelet transfusion, or surgical re-exploration
Measured: At 4 and 24 hours
Amount of allogeneic blood products
Measured: 24 hours after the start of surgery
Number of patients who do not receive any RBC transfusions or any allogeneic blood transfusions
Measured: first 24 hours after the start of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2019
- Study start24 Sep 2019
- Primary completion21 Jul 2020
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bleeding in Cardiac SurgeryStudies 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to receive either PCC or FP when the blood bank receives the first order for coagulation factor replacement and deems it to be in accordance with accepted clinical standards.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Keyvan Karkouti, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04114643
- Sponsor's protocol ID
- 19-5393
- Acronym
- FARES
- Status last verified
- Jul 2020
- First submitted
- 25 Sep 2019
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.
PubMed 36408876Karkouti K, Bartoszko J, Grewal D, Bingley C, Armali C, Carroll J, Hucke HP, Kron A, McCluskey SA, Rao V, Callum J. Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial. JAMA Netw Open. 2021 Apr 1;4(4):e213936. doi: 10.1001/jamanetworkopen.2021.3936.
PubMed 33792729
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prothrombin Complex Concentrate Versus Frozen Plasma in Bleeding Adult Cardiac Surgical Patients: A Multicentre, Randomized, Active-control, Pragmatic, Phase 2 Pilot Study
- ClinicalTrials.gov ID
- NCT04114643
- Acronym / sponsor ID
- FARES / 19-5393
- Conditions
- Bleeding in Cardiac Surgery
- Keywords
- Frozen Plasma (FP), Prothrombin Complex Concentrate (PCC), Octaplex, Coagulation Factor Replacement, Transfusion, Bleeding Cardiac Surgical Patients, Pilot, Phase 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 103 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 24 Sep 2019 (actual)
- Primary completion
- 21 Jul 2020 (actual)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 3 Oct 2019 (actual)
- 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 multicentre, randomized, active-control, pragmatic, Phase 2 pilot study in adult cardiac surgery patients. Two Canadian hospitals will participate, and it is estimated that the study will take approximately 9 months to complete.
Approximately 120 bleeding adult cardiac surgical patients who require coagulation factor replacement during cardiac surgery will be included. Patients will be randomized to receive either PCC or FP when the blood bank receives the first order for coagulation factor replacement and deems it to be in accordance with accepted clinical standards. Patients will be treated according to their assigned group on the first and second times when coagulation factor replacement is ordered during the treatment period (24 hours after randomization). For any additional doses (i.e., the third dose and thereafter), patients in both groups will receive FP (in 1U increments at the discretion of the ordering physician). No other aspects of care will be modified.
This pilot study aims to select a clinically relevant primary efficacy endpoint for a confirmative Phase 3 study, which will subsequently aim to determine if PCC is non-inferior or superior to FP in terms of effica-cy and safety in bleeding cardiac surgical patients. In the pilot study, safety outcomes will be measured for the first 28 days, which is the duration of participation of each patient in the trial.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized to receive either PCC or FP when the blood bank receives the first order for coagulation factor replacement and deems it to be in accordance with accepted clinical standards.
| Arm | Type | Receives |
|---|---|---|
| Prothrombin Complex Concentrate | Active comparator | Biological: Prothrombin Complex Concentrate |
| Frozen Plasma | Active comparator | Biological: Frozen Plasma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing any index cardiac surgery with or without CPB in whom coagulation factor replacement with PCC or FP is ordered in the operating room for:
- Management of bleeding, or
- Anticipated bleeding in a patient who has
Key exclusion criteria (10 listed)
- Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump [IABP]), or repair of thoracoabdominal aneurysm
- Critical state immediately before emergency surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before start of surgery)
- History of heparin induced thrombocytopenia
- Last preoperative INR >1.5 and patient on warfarin
- Taken dabigatran, rivaroxaban, apixaban, or edoxaban within 48 hours of start of surgery
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 |
|---|---|---|
| Prothrombin Complex ConcentrateAlso: OctaplexOctaplex will be administered when the blood bank receives an order for coagulation factor replacement | Biological | Prothrombin Complex Concentrate |
| Frozen PlasmaAlso: Fresh Frozen PlasmaFrozen Plasma will be administered when the blood bank receives an order for coagulation factor replacement | Biological | Frozen Plasma |
Primary outcome
Treatment response
Time frame: At 4 and 24 hours
Administration of hemostatic agents including a second dose of IMP, platelet transfusion, or surgical re-exploration
Amount of allogeneic blood products
Time frame: 24 hours after the start of surgery
Number of patients who do not receive any RBC transfusions or any allogeneic blood transfusions
Time frame: first 24 hours after the start of surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Derived from this study: PubMed 36408876Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.
- Derived from this study: PubMed 33792729Karkouti K, Bartoszko J, Grewal D, Bingley C, Armali C, Carroll J, Hucke HP, Kron A, McCluskey SA, Rao V, Callum J. Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial. JAMA Netw Open. 2021 Apr 1;4(4):e213936. doi: 10.1001/jamanetworkopen.2021.3936.
- 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prothrombin Complex Concentrate and Frozen Plasma in people with Bleeding in Cardiac Surgery, run by University Health Network, Toronto at 1 site 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 5 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Treatment response (time frame: At 4 and 24 hours). The study lists 3 primary outcomes in all. 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 NCT04114643, which also lists 2 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 3 Nov 2020; AzTrials last refreshed its copy on 28 Oct 2026.