Trial Outcomes & Findings for Efficacy of Prothrombin Complex Concentrate Reducing Perioperative Blood Loss in Cardiac Surgery (NCT NCT04244981)
NCT ID: NCT04244981
Last Updated: 2026-06-24
Results Overview
cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
476 participants
Primary outcome timeframe
between 1 hour after trial drug administration and 24 hours after surgery
Results posted on
2026-06-24
Participant Flow
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.
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).
Participant milestones
| Measure |
PCC Group
Four-factor PCC: 8-15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.
1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.
Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
|
FFP Group
FFP: 6-10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
|
|---|---|---|
|
Overall Study
STARTED
|
240
|
236
|
|
Overall Study
COMPLETED
|
240
|
236
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Mean age was 55 years (SD 12) in the PCC group and 55years (SD 11) in the FFP group(ASD=0.02).
Baseline characteristics by cohort
| Measure |
PCC Group
n=240 Participants
Four-factor PCC 8 -15 IU/kg
|
FFP Group
n=236 Participants
FFP 6 - 10 mL/kg
|
Total
n=476 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 years
STANDARD_DEVIATION 12 • n=20 Participants • Mean age was 55 years (SD 12) in the PCC group and 55years (SD 11) in the FFP group(ASD=0.02).
|
55 years
STANDARD_DEVIATION 11 • n=20 Participants • Mean age was 55 years (SD 12) in the PCC group and 55years (SD 11) in the FFP group(ASD=0.02).
|
55 years
STANDARD_DEVIATION 11 • n=40 Participants • Mean age was 55 years (SD 12) in the PCC group and 55years (SD 11) in the FFP group(ASD=0.02).
|
|
Sex: Female, Male
Female
|
106 Participants
n=20 Participants • There were134 (56%) male patients in the PCC group and 126 (53%) in the FFP group.
|
110 Participants
n=20 Participants • There were134 (56%) male patients in the PCC group and 126 (53%) in the FFP group.
|
216 Participants
n=40 Participants • There were134 (56%) male patients in the PCC group and 126 (53%) in the FFP group.
|
|
Sex: Female, Male
Male
|
134 Participants
n=20 Participants • There were134 (56%) male patients in the PCC group and 126 (53%) in the FFP group.
|
126 Participants
n=20 Participants • There were134 (56%) male patients in the PCC group and 126 (53%) in the FFP group.
|
260 Participants
n=40 Participants • There were134 (56%) male patients in the PCC group and 126 (53%) in the FFP group.
|
|
Race/Ethnicity, Customized
Asian
|
240 Participants
n=20 Participants • All participants were Asian.
|
236 Participants
n=20 Participants • All participants were Asian.
|
476 Participants
n=40 Participants • All participants were Asian.
|
|
New York Heart Association class
NYHA I
|
9 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
2 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
11 Participants
n=40 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
|
New York Heart Association class
NYHA II
|
80 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
75 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
155 Participants
n=40 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
|
New York Heart Association class
NYHA III
|
139 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
154 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
293 Participants
n=40 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
|
New York Heart Association class
NYHA IV
|
12 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
5 Participants
n=20 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
17 Participants
n=40 Participants • New York Heart Association (NYHA) functional classification was assessed for each participant at baseline. Class I: no limitation of physical activity Class II: slight limitation of physical activity Class III: marked limitation of physical activity Class IV: unable to carry on any physical activity without discomfort Higher NYHA class corresponds to worse functional status. Outcomes were analyzed by comparing the distribution of participants across these classes in each treatment group.
|
|
CPB duration
|
122 minutes
n=20 Participants • The cardiopulmonary bypass time was 122 minutes (IQR 98-160) in the PCC group and 120 minutes (IQR 92-159) in the FFP group.
|
120 minutes
n=20 Participants • The cardiopulmonary bypass time was 122 minutes (IQR 98-160) in the PCC group and 120 minutes (IQR 92-159) in the FFP group.
|
122 minutes
n=40 Participants • The cardiopulmonary bypass time was 122 minutes (IQR 98-160) in the PCC group and 120 minutes (IQR 92-159) in the FFP group.
|
|
Surgery type
simple
|
103 Participants
n=20 Participants • In the PCC group, 103 participants (43%) underwent simple surgery and 137 participants (57%) underwent complex surgery. In the FFP group, 101 participants (43%) underwent simple surgery and 135 participants (57%) underwent complex surgery.
|
101 Participants
n=20 Participants • In the PCC group, 103 participants (43%) underwent simple surgery and 137 participants (57%) underwent complex surgery. In the FFP group, 101 participants (43%) underwent simple surgery and 135 participants (57%) underwent complex surgery.
|
204 Participants
n=40 Participants • In the PCC group, 103 participants (43%) underwent simple surgery and 137 participants (57%) underwent complex surgery. In the FFP group, 101 participants (43%) underwent simple surgery and 135 participants (57%) underwent complex surgery.
|
|
Surgery type
complex
|
137 Participants
n=20 Participants • In the PCC group, 103 participants (43%) underwent simple surgery and 137 participants (57%) underwent complex surgery. In the FFP group, 101 participants (43%) underwent simple surgery and 135 participants (57%) underwent complex surgery.
|
135 Participants
n=20 Participants • In the PCC group, 103 participants (43%) underwent simple surgery and 137 participants (57%) underwent complex surgery. In the FFP group, 101 participants (43%) underwent simple surgery and 135 participants (57%) underwent complex surgery.
|
272 Participants
n=40 Participants • In the PCC group, 103 participants (43%) underwent simple surgery and 137 participants (57%) underwent complex surgery. In the FFP group, 101 participants (43%) underwent simple surgery and 135 participants (57%) underwent complex surgery.
|
PRIMARY outcome
Timeframe: between 1 hour after trial drug administration and 24 hours after surgeryPopulation: No participants withdrew from the trial. All analyses were conducted according to a modified intent-to-treat (mITT) approach.
cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery
Outcome measures
| Measure |
PCC Group
n=240 Participants
Four-factor PCC 8 -15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.
1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.
Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
|
FFP Group
n=236 Participants
FFP 6 -10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
|
|---|---|---|
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Cumulative Chest Tube Drainage
|
482 ml
Standard Deviation 300
|
477 ml
Standard Deviation 316
|
SECONDARY outcome
Timeframe: from 1 hour after trial drug administration to 24 hours after surgeryPopulation: No participants withdrew from the trial. All analyses were conducted according to a modified intent-to-treat (mITT) approach.
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.
Outcome measures
| Measure |
PCC Group
n=240 Participants
Four-factor PCC 8 -15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.
1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.
Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
|
FFP Group
n=236 Participants
FFP 6 -10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
|
|---|---|---|
|
Efficacy of Haemostasis
|
196 Participants
|
169 Participants
|
SECONDARY outcome
Timeframe: between 1 hour after trial drug administration and 24 hours after surgery； and between 1 hour after trial drug administration and 7 days postoperativelythe cumulated allogenic Red blood cells (RBC) units transfused
Outcome measures
| Measure |
PCC Group
n=240 Participants
Four-factor PCC 8 -15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.
1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.
Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
|
FFP Group
n=236 Participants
FFP 6 -10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
|
|---|---|---|
|
Allogeneic RBCs Units Transfused
RBC transfused between 1 hour after trial drug administration and 7 days after surgery
|
0 units
Interval 0.0 to 0.0
|
0 units
Interval 0.0 to 0.0
|
|
Allogeneic RBCs Units Transfused
RBC transfused between 1 hour after trial drug administration and 24 hours after surgery
|
0 units
Interval 0.0 to 0.0
|
0 units
Interval 0.0 to 0.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: between the preoperative period and the first postoperative morningChanges in aPTT, INR, fibrinogen levels, platelet count, and hemoglobin between the preoperative period and the first postoperative morning
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: from admission to dischargethe length(days) of ICU stay and total hospital stay
Outcome measures
Outcome data not reported
Adverse Events
PCC Group
Serious events: 2 serious events
Other events: 17 other events
Deaths: 3 deaths
FFP Group
Serious events: 1 serious events
Other events: 18 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
PCC Group
n=240 participants at risk
Four-factor PCC 8 -15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.
1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.
Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
|
FFP Group
n=236 participants at risk
FFP 6 -10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
|
|---|---|---|
|
Nervous system disorders
stroke
|
0.83%
2/240 • 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).
|
0.00%
0/236 • 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).
|
|
Vascular disorders
venous thrombosis
|
0.00%
0/240 • 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).
|
0.42%
1/236 • 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).
|
Other adverse events
| Measure |
PCC Group
n=240 participants at risk
Four-factor PCC 8 -15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.
1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.
Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
|
FFP Group
n=236 participants at risk
FFP 6 -10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
|
|---|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
7.1%
17/240 • 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).
|
7.6%
18/236 • 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).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place