BleedingPhase 2PROPHESYNCT03715348
Trial of PCC Versus FFP in Patients Undergoing Heart Surgery
A Phase 2 study testing Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma in people with Bleeding and Surgery, run by Queen Mary University of London at 1 site in United Kingdom.
Trial summary
The PROPHESY trial is a single centre pilot trial investigating Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC) treatment for patients who are bleeding during cardiac surgery, and who are NOT receiving a vitamin K antagonist agent (e.g. warfarin). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bleeding, Surgery, Transfusion
- What is being tested?
- Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2019to 29 Jan 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
- Age ≥18 years
- Able to give consent
- Any cardiovascular surgeries excluding procedures under exclusion criteria
Who cannot join
- Unable to consent
- Patients refusing blood transfusion for any reason
- First time isolated coronary artery bypass grafts (CABG)
- First time isolated aortic valve replacement (excluding active endocarditis)
- Thoraco-abdominal surgeries
- Minor surgeries that do not involve cardiopulmonary bypass
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- Use of warfarin within four days
- Use of direct oral anticoagulants (i.e. dabigatran, rivaroxaban, apixaban or edoxaban) within 48 hrs (or 72 hours if patient has renal impairment - i.e. estimated glomerular filtration rate of <30ml/min)
- Inherited bleeding disorder (i.e. any inherited clotting factor deficiencies, or platelet disorders)
- Pregnancy
- Known or suspected allergy to FFP or PCC
- Known or suspected allergy to heparin, Sodium citrate dihydrate, sodium dihydrogenphosphate dihydrate and Glycine
- History of Heparin-induced thrombocytopenia
- Individuals who have Immunoglobulin A (IgA) deficiency with known antibodies against IgA
- Documented venous thromboembolism in the last three months
- Documented antiphospholipid syndrome
- Severe protein S deficiency
- Participation in another clinical trial, where the patient has received Investigational Medicinal Product in the last 3 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pragmatic Pilot Randomised Phase II Controlled Trial of Prothrombin Complex Concentrates (PCC) Versus Fresh Frozen Plasma (FFP) in Adult Patients Who Are Undergoing Heart Surgery
The PROPHESY trial is a single centre pilot trial investigating Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC) treatment for patients who are bleeding during cardiac surgery, and who are NOT receiving a vitamin K antagonist agent (e.g. warfarin).
This pilot study will investigate the feasibility of delivering the different components of the trial, so that investigators can determine if it's feasible to move to a future large trial that will aim to compare the efficacy and safety of FFP versus PCC in adult patients who are actively bleeding during cardiac surgery.
Read the detailed description
There are ~ 30,000 cardiac procedures performed each year in the United Kingdom (UK), and it is estimated that ~30% of these cases require plasma transfusion for management of bleeding during cardiovascular surgery. Bleeding after cardiac surgery that requires blood transfusion is associated with significant morbidity and mortality, resulting in substantial costs to the health service.
There have been no clinical trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery in patients who are bleeding, and who are not on vitamin K antagonists. In the UK, FFP transfusion is the standard treatment for management of bleeding: however, the use of PCC in this setting is rising, with several observational studies now demonstrating that it is safe, and that its administration is associated with reduced blood transfusion requirements, albeit no difference in other outcomes. Potential advantages of PCC over FFP are: increased concentration of clotting factors leading to faster improvement of reversing coagulopathy; improved ease and speed of administration; reduced fluid volume; and reduced incidence of immune modulatory side effects.
While observational studies have suggested that PCC can be safely administered in bleeding patients undergoing cardiac surgery, the clinical equipoise and, the lack of high quality evidence means that a randomised control trial is required to compare the clinical efficacy and safety of both in bleeding patients undergoing cardiac surgery not relating to warfarin. Prior to such a trial, the investigators will perform a single-centre pilot study to assess if individual components of a large trial are deliverable.
- Conditions
- Bleeding, Surgery, Transfusion
- Being tested
- Prothrombin Complex Concentrate (PCC), Fresh Frozen Plasma
- Keywords
- fresh frozen plasma, prothrombin complex concentrate, cardiac surgery
- Medical subject headings
- Hemorrhage, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prothrombin Complex Concentrate (PCC)Drug
PCC is a blood product produced through pooling of thousands of human plasmas, which is then treated to inactivate enveloped viruses. From the pooled plasma, vitamin K dependent clotting factors (factors II, VII, IX and X, and protein C and protein S), are selected to produce the concentrated form called PCC.
Fresh Frozen PlasmaBiological
Fresh Frozen Plasma a blood component manufactured from whole blood collection.
| Study group | Role | What they receive |
|---|---|---|
| Fresh Frozen Plasma (FFP) | Active comparator | Patients randomised to the comparator arm will receive Fresh Frozen Plasma (FFP)
FFP will be provide as a solution for intravenous administration, once thawed.
The dose of the FFP will be ~ 15 mL/kg.
Subjects may receive multiple doses of FFP as required if bleeding continues, as per usual care Receives: Biological: Fresh Frozen Plasma |
| Prothrombin Complex Concentrate (PCC) | Experimental | Patients randomised to the experimental arm will receive PCC at ~15 IU/kg. PCC will be reconstituted into a solution for intravenous administration.
Subjects will receive a single dose of PCC, and if bleeding continues, standard treatment will be administered Receives: Drug: Prothrombin Complex Concentrate (PCC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment rate
Proportion of eligible patients who consent to the study Proportion of patients who have consented and who bleed within 24 hours and who require FFP transfusion.
Measured: Within 24 hours of surgery
Secondary outcomes (4)
Delivery of different components of the trial to see if a larger trial is feasible
The data collected from different trial componenets, such as study drugs administration, study procedure adherence and analysis of clinical outcome data will be combined and assessed to see whether it is feasible to successfully run this pilot as a larger, multi-centre trial
Measured: Collected at 90 days or death, whichever occurs first
To compare the impact of FFP and PCC on the haemostatic capacity of bleeding patients after cardiac surgery
Routine clotting tests and additional clotting tests will be performed to measure clotting factor levels, markers for clotting and anticoagulant activity in patients receiving FFP compare to PCC
Measured: Within 24 hours of surgery
Qualitative research involving completion of a Delphi survey to apprise the management and conduct of a larger trial
Using the Delphi survey, information will be obtained from patient and public involvement (PPI) and healthcare professionals on the design/running of the larger trial, in order to understand how best to optimise identification and recruitment of participants, and to improve adherence to the trial procedures and protocol.
Measured: Completed over a 4 month period during the study follow-up stage
Qualitative research involving interviews of patients and healthcare professionals involved in PROPHESY to apprise the management and conduct of a larger trial
Interviews will be conducted with 6 study subjects and 8 healthcare professionals involved in the PROPHESY trial to inform on the key aspects for the successful conduct and mangement of a larger trial
Measured: By the 90 days end of study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study start1 Mar 2019
- Primary completion29 Jan 2020
- Study completion29 Jan 2020
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 BleedingStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe 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
- Pragmatic pilot, open label, phase II randomised controlled trial
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Sponsor
- Investigators
- Laura Green, MBBS MsC MD(Res) MRCP FRCPath, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03715348
- Sponsor's protocol ID
- 012507
- Other IDs
- 2018-003041-41, 2018
- Acronym
- PROPHESY
- Status last verified
- Sep 2018
- First submitted
- 8 Oct 2018
- Last updated
- 17 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Study results will be published in peer review journals and presented at national/international scientific meetings. The sponsor retains the right to review all publications prior to submission. Responsibility for ensuring accuracy of any publication from this study is delegated to the Chief Investigator.
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 36408876Green L, Roberts N, Cooper J, Field J, Gill R, Klein A, Agarwal S, Stanworth S, Johnston A, Monk V, O'Brien B. A pragmatic pilot phase II randomised controlled trial of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) in adult patients who are undergoing heart surgery (PROPHESY). Trials. 2019 Dec 9;20(1):684. doi: 10.1186/s13063-019-3759-8.
PubMed 31815658
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic Pilot Randomised Phase II Controlled Trial of Prothrombin Complex Concentrates (PCC) Versus Fresh Frozen Plasma (FFP) in Adult Patients Who Are Undergoing Heart Surgery
- ClinicalTrials.gov ID
- NCT03715348
- Acronym / sponsor ID
- PROPHESY / 012507
- Conditions
- Bleeding, Surgery, Transfusion
- Keywords
- fresh frozen plasma, prothrombin complex concentrate, cardiac surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 29 Jan 2020 (actual)
- Study completion
- 29 Jan 2020 (actual)
- First posted
- 23 Oct 2018 (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.
The PROPHESY trial is a single centre pilot trial investigating Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC) treatment for patients who are bleeding during cardiac surgery, and who are NOT receiving a vitamin K antagonist agent (e.g. warfarin).
This pilot study will investigate the feasibility of delivering the different components of the trial, so that investigators can determine if it's feasible to move to a future large trial that will aim to compare the efficacy and safety of FFP versus PCC in adult patients who are actively bleeding during cardiac surgery.
Detailed description
There are ~ 30,000 cardiac procedures performed each year in the United Kingdom (UK), and it is estimated that ~30% of these cases require plasma transfusion for management of bleeding during cardiovascular surgery. Bleeding after cardiac surgery that requires blood transfusion is associated with significant morbidity and mortality, resulting in substantial costs to the health service.
There have been no clinical trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery in patients who are bleeding, and who are not on vitamin K antagonists. In the UK, FFP transfusion is the standard treatment for management of bleeding: however, the use of PCC in this setting is rising, with several observational studies now demonstrating that it is safe, and that its administration is associated with reduced blood transfusion requirements, albeit no difference in other outcomes. Potential advantages of PCC over FFP are: increased concentration of clotting factors leading to faster improvement of reversing coagulopathy; improved ease and speed of administration; reduced fluid volume; and reduced incidence of immune modulatory side effects.
While observational studies have suggested that PCC can be safely administered in bleeding patients undergoing cardiac surgery, the clinical equipoise and, the lack of high quality evidence means that a randomised control trial is required to compare the clinical efficacy and safety of both in bleeding patients undergoing cardiac surgery not relating to warfarin. Prior to such a trial, the investigators will perform a single-centre pilot study to assess if individual components of a large trial are deliverable.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pragmatic pilot, open label, phase II randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| Fresh Frozen Plasma (FFP) | Active comparator | Biological: Fresh Frozen PlasmaPatients randomised to the comparator arm will receive Fresh Frozen Plasma (FFP) FFP will be provide as a solution for intravenous administration, once thawed. The dose of the FFP will be ~ 15 mL/kg. Subjects may receive multiple doses of FFP as required if bleeding continues, as per usual care |
| Prothrombin Complex Concentrate (PCC) | Experimental | Drug: Prothrombin Complex Concentrate (PCC)Patients randomised to the experimental arm will receive PCC at ~15 IU/kg. PCC will be reconstituted into a solution for intravenous administration. Subjects will receive a single dose of PCC, and if bleeding continues, standard treatment will be administered |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥18 years
- Able to give consent
- Any cardiovascular surgeries excluding procedures under exclusion criteria
Key exclusion criteria (18 listed)
- Unable to consent
- Patients refusing blood transfusion for any reason
- First time isolated coronary artery bypass grafts (CABG)
- First time isolated aortic valve replacement (excluding active endocarditis)
- Thoraco-abdominal surgeries
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 Concentrate (PCC)PCC is a blood product produced through pooling of thousands of human plasmas, which is then treated to inactivate enveloped viruses. From the pooled plasma, vitamin K dependent clotting factors (factors II, VII, IX and X, and protein C and protein S), are selected to produce the concentrated form called PCC. | Drug | Prothrombin Complex Concentrate (PCC) |
| Fresh Frozen PlasmaFresh Frozen Plasma a blood component manufactured from whole blood collection. | Biological | Fresh Frozen Plasma (FFP) |
Primary outcome
Recruitment rate
Time frame: Within 24 hours of surgery
Proportion of eligible patients who consent to the study Proportion of patients who have consented and who bleed within 24 hours and who require FFP transfusion.
4 secondary outcomes
Delivery of different components of the trial to see if a larger trial is feasible
Time frame: Collected at 90 days or death, whichever occurs first
To compare the impact of FFP and PCC on the haemostatic capacity of bleeding patients after cardiac surgery
Time frame: Within 24 hours of surgery
Qualitative research involving completion of a Delphi survey to apprise the management and conduct of a larger trial
Time frame: Completed over a 4 month period during the study follow-up stage
Qualitative research involving interviews of patients and healthcare professionals involved in PROPHESY to apprise the management and conduct of a larger trial
Time frame: By the 90 days end of study visit
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 17 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 31815658Green L, Roberts N, Cooper J, Field J, Gill R, Klein A, Agarwal S, Stanworth S, Johnston A, Monk V, O'Brien B. A pragmatic pilot phase II randomised controlled trial of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) in adult patients who are undergoing heart surgery (PROPHESY). Trials. 2019 Dec 9;20(1):684. doi: 10.1186/s13063-019-3759-8.
- Individual participant dataSharing planned: No. Study results will be published in peer review journals and presented at national/international scientific meetings. The sponsor retains the right to review all publications prior to submission. Responsibility for ensuring accuracy of any publication from this study is delegated to the Chief Investigator.
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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.
Laura Green, MBBS MsC MD(Res) MRCP FRCPath principal investigator
Queen Mary University of London
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 (PCC) and Fresh Frozen Plasma in people with Bleeding and Surgery, run by Queen Mary University of London at 1 site in United Kingdom.
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 3 inclusion and 18 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 17 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 United Kingdom. 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?
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?
Recruitment rate (time frame: Within 24 hours of surgery). 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 NCT03715348, 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 17 Nov 2020.