Valvular Heart Surgery
Conditions
Keywords
prothrombin complex concentrate, fresh frozen plasma, efficacy, cardiopulmonary bypass, haemostasis
Brief summary
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.
Detailed description
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.
Interventions
Cross-Reference to FFP group.
DRUGFresh Frozen Plasma
All patients have valve surgery via median sternotomy with general anaesthesia and CPB. Mild hypothermia (32-34 ℃) is maintained during bypass, with patients thereafter being rewarmed to a nasopharyngeal temperature of 37.0 ℃ and a rectal temperature of 35.5 ℃. Heparin (400 IU/kg) is given before initiation of CPB, and ACT is maintained above 480 seconds. Tranexamic acid is administered as a 20-mg/kg bolus within the first hour, followed by an infusion of 2 mg/kg per hour infusion until the end of surgery. After CPB, heparin is neutralised with protamine sulphate (1 mg per 100 IU heparin), targeting an ACT within ±10% of the baseline value; an additional 20-30 mg is given if ACT remains elevated. FFP or PCC, per randomization, is given once post-CPB coagulation factor deficiency is confirmed.
Sponsors
SHI Jia
Peking Union Medical College Hospital
Beijing Anzhen Hospital
Guizhou Provincial People's Hospital
Zunyi Medical College
First Affiliated Hospital of Harbin Medical University
The First Affiliated Hospital of Air Force Medicial University
The Affiliated Hospital Of Guizhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Chest Tube Drainage | between 1 hour after trial drug administration and 24 hours after surgery | cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Haemostasis | from 1 hour after trial drug administration to 24 hours after surgery | Effectiveness of haemostasis if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation. Hemostatic interventions included surgical reoperation for bleeding, transfusion of any allogeneic blood products (excluding red blood cells), or administration of any coagulation factor concentrate. |
| Allogeneic RBCs Units Transfused | between 1 hour after trial drug administration and 24 hours after surgery； and between 1 hour after trial drug administration and 7 days postoperatively | the cumulated allogenic Red blood cells (RBC) units transfused |
Countries
China
Contacts
STUDY_CHAIRLijian Pei, M.D.
Peking Union Medical College Hospital
PRINCIPAL_INVESTIGATORJia Shi, M.D.
Chinese Academy of Medical Sciences, Fuwai Hospital
Participant flow
Recruitment details
1900 participants scheduled for valvular heart surgery were screened for inclusion. Among them, 1068 patients were eligible and consented, and 476 with post-CPB coagulation factor deficiency were randomised intraoperatively to PCC or FFP.
Pre-assignment details
1424 patients were excluded due to hepatic dysfunction or coagulopathy before surgery (642), PCC treatment required by surgeons (152), decline to participate (38), not meeting the criterion for post-CPB coagulation factor deficiency (592).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 11 |
| CPB duration | 122 minutes |
| New York Heart Association class NYHA I | 9 Participants |
| New York Heart Association class NYHA II | 155 Participants |
| New York Heart Association class NYHA III | 154 Participants |
| New York Heart Association class NYHA IV | 12 Participants |
| Race/Ethnicity, Customized Asian | 240 Participants |
| Sex: Female, Male Female | 106 Participants |
| Sex: Female, Male Male | 260 Participants |
| Surgery type complex | 272 Participants |
| Surgery type simple | 204 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 240 | 1 / 236 |
| other Total, other adverse events | 17 / 240 | 18 / 236 |
| serious Total, serious adverse events | 2 / 240 | 1 / 236 |
Outcome results
None listed