Trial of PCC Versus FFP in Patients Undergoing Heart Surgery (PROPHESY)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03715348|
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : March 14, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Bleeding Surgery Transfusion||Drug: Prothrombin Complex Concentrate (PCC) Biological: Fresh Frozen Plasma||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Pragmatic pilot, open label, phase II randomised controlled trial|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 1, 2019|
|Estimated Primary Completion Date :||May 31, 2020|
|Estimated Study Completion Date :||September 1, 2020|
Active Comparator: Fresh Frozen Plasma (FFP)
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
Biological: Fresh Frozen Plasma
Fresh Frozen Plasma a blood component manufactured from whole blood collection.
Experimental: 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
Drug: 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.
- 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.
- 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 ]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
- 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 ]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
- 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 ]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.
- 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 ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03715348
|Contact: Vivienne Monk||0207 882 email@example.com|
|Contact: Jane Fieldfirstname.lastname@example.org|
|St Bartholomew's Hospital||Recruiting|
|London, United Kingdom, EC1A 7BE|
|Contact: Laura Green email@example.com|
|Contact: Neil Roberts firstname.lastname@example.org|
|Principal Investigator: Laura Green|
|Sub-Investigator: Neil Roberts|
|Sub-Investigator: Ben O'Brien|
|Principal Investigator:||Laura Green, MBBS MsC MD(Res) MRCP FRCPath||Queen Mary University of London|