At a meeting on February 17, 2025, the Data and Safety Monitoring Board recommended early termination because the predefined efficacy boundary was crossed.

This non-inferiority, randomized controlled trial aims to evaluate whether coagulation-guided low-dose four-factor prothrombin complex concentrate (PCC) is non-inferior to fresh frozen plasma (FFP) in reducing cumulative chest tube drainage from 1 hour after trial drug administration to 24 hours after surgery in patients undergoing valvular heart surgery.

Patients undergoing elective valvular heart surgery who develop post-cardiopulmonary bypass coagulation factor deficiency will be enrolled in this study. Participants will be randomly assigned to one of two groups: the PCC group or the FFP group.

Intervention: Patients in the PCC group will receive 8-15 IU/kg four-factor prothrombin complex concentrate, while those in the FFP group will receive 6-10 mL/kg fresh frozen plasma, guided by coagulation monitoring results.

The primary hypothesis is that coagulation-guided low-dose PCC is non-inferior to FFP in reducing cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery.

The secondary hypotheses are that PCC provides better haemostasis and reduces the number of red blood cell units transfused between 1 hour after trial drug administration and 24 hours after surgery, as well as within 7 days postoperatively.

This study is designed to provide evidence on whether coagulation-guided low-dose PCC can serve as an effective and safe alternative to FFP in managing post-cardiopulmonary bypass coagulopathy during valvular heart surgery.

Inclusion Criteria:

1. Age between 18 and 80 years.
2. Undergoing elective valve repair, valve replacement or complex valvular surgery through CPB.
3. Signing of the informed consent form.
4. A combined assessment of plasma activated partial thromboplastin time (plasma-aPTT) and activated clotting time (ACT) is performed 20 minutes after heparin neutralization following CPB. We considered patients who meet the following criteria to have post-CPB coagulation factor deficiencies: (1) at least moderate bleeding, as determined using a validated bleeding severity scale; (2) a targeted ACT within ±10% of baseline; and (3) a plasma-aPTT exceeding 45 seconds or more than 1.5 times baseline. The requirement could be waived when bleeding was severe and required immediate intervention.

Exclusion Criteria:

1. History of cardiac surgery.
2. Severe hepatic and renal dysfunction before surgery.
3. Coagulopathy before surgery, including inherited or acquired coagulation factor deficiencies, thrombocytopenia, platelet dysfunction and other bleeding disorders.
4. Patients undergoing emergency surgery in whom discontinuation of anticoagulant therapy was not feasible [INR > 1.2（or above upper normal limit）after discontinued use of warfarin; withdrawal of clopidogrel less than 5 days and low molecular weight heparin less than 12 hours before surgery, etc].
5. Allergy to allogeneic blood products.
6. Pregnancy.
7. Other serious diseases that may affect patient survival time, such as cancers.

Individual participant data (IPD) underlying published results will be available upon reasonable request. Specific IPD could be obtained from the principal investigator, Dr. Lijian Pei (hazelbeijing@vip.163.com).

IPD will be made available beginning 6 months after publication of the primary results and for up to 5 years thereafter.

Researchers who provide a methodologically sound proposal may request access to the IPD for the purposes of independent verification or secondary analysis. Requests should be submitted by email to the corresponding investigator (hazelbeijing@vip.163.com). Access will be granted after review and approval by the study team.

There were 3 protocol deviations: one patient in the PCC group was given FFP, and two patients in the FFP group were given PCC due to temporary unavailability of the assigned product.

Safety outcomes included serious adverse events (SAEs) and death within 30 days after surgery, with particular attention to thromboembolic complications.

The thromboembolic complications included deep vein thrombosis, pulmonary embolism, and stroke (embolic stroke, and ischemia stroke).

A limitation of our trial is that emergency cases were excluded because anticoagulants could not be stopped early enough which would complicate haemostatic management. Most participants were Asians who lived at elevations below 2000 m; results may differ in other populations or high-altitude settings. PCC use was off-label; after surgery, clinicians therefore generally preferred FFP over PCC. Furthermore, the non-inferiority margin of 200 mL for 24-hour blood loss was based on clinical consensus

Allocation is concealed with a secure web-based system which investigators access only after patients meet the criteria for post-CPB coagulation factor deficiency.Research nurses at each centre who are not involved in patient care or follow-up prepared equal volumes of trial medications. Opaque brown syringes and infusion tubing labelled "trial drug" are provided to anaesthesiologists when consenting participants meet eligibility criteria. Consequently, all patients, members of the healthcare team, and outcome assessors are fully blinded to treatment allocation. In emergency situations, such as rapid deterioration in a participant's clinical conditions, anaesthesiologists could adjust the infusion rate or discontinue the study medication. Unmasking could also be requested if deemed necessary for clinical management.