Trial of PCC Versus FFP in Patients Undergoing Heart Surgery

NCT ID: NCT03715348

Last Updated: 2020-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2020-01-29

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.

Conditions

Bleeding; Surgery; Transfusion

Keywords

fresh frozen plasma; prothrombin complex concentrate; cardiac surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Fresh Frozen Plasma

Intervention Type: BIOLOGICAL

Fresh Frozen Plasma a blood component manufactured from whole blood collection.

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

Group Type: EXPERIMENTAL

Prothrombin Complex Concentrate (PCC)

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Fresh Frozen Plasma

Fresh Frozen Plasma a blood component manufactured from whole blood collection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Able to give consent

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

British Heart Foundation

OTHER

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laura Green, MBBS MsC MD(Res) MRCP FRCPath

Role: PRINCIPAL_INVESTIGATOR

Queen Mary University of London

Locations

St Bartholomew's Hospital

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36408876 (View on PubMed)

Green 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.

Reference Type: DERIVED

PMID: 31815658 (View on PubMed)

Other Identifiers

2018-003041-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

012507

Identifier Type: -

Identifier Source: org_study_id