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Trial of PCC Versus FFP in Patients Undergoing Heart Surgery (PROPHESY)

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ClinicalTrials.gov Identifier: NCT03715348
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
British Heart Foundation
Information provided by (Responsible Party):
Queen Mary University of London

Tracking Information
First Submitted Date  ICMJE October 8, 2018
First Posted Date  ICMJE October 23, 2018
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE March 1, 2019
Estimated Primary Completion Date May 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03715348 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of PCC Versus FFP in Patients Undergoing Heart Surgery
Official Title  ICMJE 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
Brief 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).

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Pragmatic pilot, open label, phase II randomised controlled trial
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Bleeding
  • Surgery
  • Transfusion
Intervention  ICMJE
  • 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.
  • Biological: Fresh Frozen Plasma
    Fresh Frozen Plasma a blood component manufactured from whole blood collection.
Study Arms  ICMJE
  • 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

    Intervention: Biological: Fresh Frozen Plasma
  • 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

    Intervention: Drug: Prothrombin Complex Concentrate (PCC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 18, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2020
Estimated Primary Completion Date May 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years
  • Able to give consent
  • Any cardiovascular surgeries excluding procedures under exclusion criteria

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vivienne Monk 0207 882 5668 cvctu@qmul.ac.uk
Contact: Jane Field 02078823416 jane.field@qmul.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03715348
Other Study ID Numbers  ICMJE 012507
2018-003041-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description:

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.

Responsible Party Queen Mary University of London
Study Sponsor  ICMJE Queen Mary University of London
Collaborators  ICMJE British Heart Foundation
Investigators  ICMJE
Principal Investigator: Laura Green, MBBS MsC MD(Res) MRCP FRCPath Queen Mary University of London
PRS Account Queen Mary University of London
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP