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

Queen Mary University of London

Status and phase: Completed; Phase 2

Conditions: Surgery; Transfusion; Bleeding

Treatments: Biological: Fresh Frozen Plasma; Drug: Prothrombin Complex Concentrate (PCC)

Study type: Interventional

Funder types: Other

Identifiers

NCT03715348

2018-003041-41 (EudraCT Number)

012507

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Fresh Frozen Plasma (FFP)

Active Comparator group

Description:

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

Treatment:

Biological: Fresh Frozen Plasma

Prothrombin Complex Concentrate (PCC)

Experimental group

Description:

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

Treatment:

Drug: Prothrombin Complex Concentrate (PCC)