Trial of PCC Versus FFP in Patients Undergoing Heart Surgery

NCT03715348 | Completed Phase 2 DMC

• 2 other identifiers: 0125072018-003041-41
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Bleeding; Surgery; Transfusion

Keywords

fresh frozen plasma; prothrombin complex concentrate; cardiac surgery

Outcome Measures

Primary Outcomes (1)

• Recruitment rate

  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.

  Within 24 hours of surgery

Secondary Outcomes (4)

• Delivery of different components of the trial to see if a larger trial is feasible

  Collected at 90 days or death, whichever occurs first

• To compare the impact of FFP and PCC on the haemostatic capacity of bleeding patients after cardiac surgery

  Within 24 hours of surgery

• Qualitative research involving completion of a Delphi survey to apprise the management and conduct of a larger trial

  Completed over a 4 month period during the study follow-up stage

• Qualitative research involving interviews of patients and healthcare professionals involved in PROPHESY to apprise the management and conduct of a larger trial

  By the 90 days end of study visit

Study Arms (2)

Fresh Frozen Plasma (FFP)

ACTIVE COMPARATOR

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

Prothrombin Complex Concentrate (PCC)

EXPERIMENTAL

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)

Interventions

Prothrombin Complex Concentrate (PCC) 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.

Prothrombin Complex Concentrate (PCC)

Fresh Frozen Plasma BIOLOGICAL

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

Fresh Frozen Plasma (FFP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Able to give consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Queen Mary University of London: lead
• British Heart Foundation: collaborator

Study Sites (1)

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36408876 DERIVED

• 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.

  PMID: 31815658 DERIVED

MeSH Terms

Conditions

Hemorrhage; Hemophilia B

Interventions

Factor IX

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Laura Green, MBBS MsC MD(Res) MRCP FRCPath

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pragmatic pilot, open label, phase II randomised controlled trial

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 23, 2018
• Study Start: March 1, 2019
• Primary Completion: January 29, 2020
• Study Completion: January 29, 2020
• Last Updated: November 17, 2020

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)