Clinical trial NCT03715348: Trial of PCC Versus FFP in Patients Undergoing Heart Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bleeding
Surgery
Transfusion
Keywords: fresh frozen plasma
prothrombin complex concentrate
cardiac surgery
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2018-10-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic pilot, open label, phase II randomised controlled trial
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment rate
timeFrame: Within 24 hours of surgery
Secondary outcomes:
measure: Delivery of different components of the trial to see if a larger trial is feasible
timeFrame: Collected at 90 days or death, whichever occurs first
measure: To compare the impact of FFP and PCC on the haemostatic capacity of bleeding patients after cardiac surgery
timeFrame: Within 24 hours of surgery
measure: Qualitative research involving completion of a Delphi survey to apprise the management and conduct of a larger trial
timeFrame: Completed over a 4 month period during the study follow-up stage
measure: Qualitative research involving interviews of patients and healthcare professionals involved in PROPHESY to apprise the management and conduct of a larger trial
timeFrame: By the 90 days end of study visit
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
Study officials:
affiliation: Queen Mary University of London
name: Laura Green, MBBS MsC MD(Res) MRCP FRCPath
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.