Bleeding, Blood Loss, Surgical, Cardiovascular Surgical Procedures, Fresh Frozen Plasma, Prothrombin Complex Concentrates
Conditions
Brief summary
This will be the first prospective randomized controlled clinical trial directly comparing Prothrombin Complex Concentrate (PCC) Compared to Fresh Frozen Plasma (FFP) for post cardiopulmonary bypass microvascular bleeding and factor-mediated coagulopathy. Is there a difference in bleeding and transfusion requirements in patients received PCC versus FFP?
Interventions
DRUGProthrombin complex concentrate (Human)
PCC (Kcentra)
BIOLOGICALFresh frozen plasma (FFP)
FFP
Sponsors
CSL Behring
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
All subjects accepted for this study must: * Be 18 years of age * Be undergoing elective cardiac surgical procedure utilizing cardiopulmonary bypass * Have evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team in addition to a PT \>16.6 sec or INR \>1.6 sec.
Exclusion criteria
Subjects who have one or more of the following will be excluded from the study: * Are unable to grant informed consent or comply with study procedure * History of hypercoagulable condition (e.g. Factor V Leiden, AT-3 deficiency, Prothrombin gene mutation, Anti-phospholipid antibody syndrome, etc) or previous unprovoked thromboembolic complications * Coagulopathic conditions such as factor deficiencies, factor inhibitors, heparin induced thrombocytopenia, or use of intravenous anticoagulants other than heparin at the time of cardiovascular surgery * Thromboembolic event within past 3 months * Received oral therapy with clopidogrel, prasugrel, rivaroxaban or dabigatran within the past 5 days * Patients taking chronic warfarin therapy who have not discontinued treatment and demonstrated an INR \<1.3 prior to surgery * Fibrinogen level \<150 mg/dL on initial post cardiopulmonary bypass labs * Antithrombin 3 level \< 80% control (preoperative) * Are undergoing emergency open heart-surgery * Cardiopulmonary bypass time is expected to be \< 30 minutes * Age \< 18 years of age * Are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chest Tube Output | 24 hours | The amount of chest tube drainage output from after surgery through midnight of the next day. As measured in mL. |
| Red Blood Cell (RBC) Blood Product Transfusion | 24 hours | The number of subject's who received 0,1,2,3 or more units of RBC's transfused from completion of study drug administration though midnight of the next day. |
| Platelets Blood Product Transfusion | 24 hours | The number of subject's who received 0,1,2,3 or more units of Platelets transfused from completion of study drug administration though midnight of the next day. |
| Cryoprecipitate (Cryo) Blood Product Transfusion | 24 hours | The number of subject's who received 0,1,2,3 or more units of Cryo's transfused from completion of study drug administration though midnight of the next day. |
| Fresh Frozen Plasma (FFP) Blood Product Transfusion | 24 hours | The number of subject's who received 0,1,2,3 or more units of FFP's transfused from completion of study drug administration though midnight of the next day. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fresh Frozen Plasma After cardiopulmonary bypass, patients received protamine at dose 0.01 mg/unit of heparin given with target activated clotting time (ACT) within 10% of baseline value. After protamine administration the ACT, complete blood count (CBC), prothrombin time (PT)/ international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen, were collected via preexisting arterial access. If ACT \>10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 10 minutes after return of ACT to within 10% of baseline. Patients with clinical evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team, along with a PT \>16.6 sec/ INR \>1.6 sec received fresh frozen plasma as this is standard therapy per our institutional algorithm at a dose of 10-15 mL/kg rounded up to the nearest unit.
Fresh frozen plasma (FFP): FFP | 49 |
| Prothrombin Complex Concentrate After cardiopulmonary bypass, patients received protamine at dose 0.01 mg/unit of heparin given with target activated clotting time (ACT) within 10% of baseline value. After protamine administration the ACT, complete blood count (CBC), prothrombin time (PT)/ international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen, were collected via preexisting arterial access. If ACT \>10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 10 minutes after return of ACT to within 10% of baseline. Patients with clinical evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team, along with a PT \>16.6 sec/ INR \>1.6 sec received Prothrombin complex concentrate (Human) 15 units/kg.
Prothrombin complex concentrate (Human): PCC (Kcentra) | 51 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Prothrombin Complex Concentrate | Fresh Frozen Plasma | Total |
|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 12.8 | 65.6 years STANDARD_DEVIATION 14.6 | 66.8 years STANDARD_DEVIATION 13.7 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 50 Participants | 48 Participants | 98 Participants |
| Region of Enrollment United States | 51 participants | 49 participants | 100 participants |
| Sex: Female, Male Female | 25 Participants | 14 Participants | 39 Participants |
| Sex: Female, Male Male | 26 Participants | 35 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 49 | 1 / 51 |
| other Total, other adverse events | 0 / 49 | 0 / 51 |
| serious Total, serious adverse events | 44 / 49 | 45 / 51 |
Outcome results
Primary
Chest Tube Output
The amount of chest tube drainage output from after surgery through midnight of the next day. As measured in mL.
Time frame: 24 hours
Population: 1 subject's data was not collected nor analyzed for the FFP arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fresh Frozen Plasma | Chest Tube Output | 1022 mL |
| Prothrombin Complex Concentrate | Chest Tube Output | 937 mL |
p-value: 0.8495% CI: [0.81, 1.19]Regression, Linear
Primary
Cryoprecipitate (Cryo) Blood Product Transfusion
The number of subject's who received 0,1,2,3 or more units of Cryo's transfused from completion of study drug administration though midnight of the next day.
Time frame: 24 hours
Population: 1 subject's data was not collected nor analyzed for the FFP arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fresh Frozen Plasma | Cryoprecipitate (Cryo) Blood Product Transfusion | 0 units | 40 Participants |
| Fresh Frozen Plasma | Cryoprecipitate (Cryo) Blood Product Transfusion | 1 unit | 2 Participants |
| Fresh Frozen Plasma | Cryoprecipitate (Cryo) Blood Product Transfusion | 2 units | 5 Participants |
| Fresh Frozen Plasma | Cryoprecipitate (Cryo) Blood Product Transfusion | 3 or more units | 1 Participants |
| Prothrombin Complex Concentrate | Cryoprecipitate (Cryo) Blood Product Transfusion | 3 or more units | 1 Participants |
| Prothrombin Complex Concentrate | Cryoprecipitate (Cryo) Blood Product Transfusion | 0 units | 40 Participants |
| Prothrombin Complex Concentrate | Cryoprecipitate (Cryo) Blood Product Transfusion | 2 units | 8 Participants |
| Prothrombin Complex Concentrate | Cryoprecipitate (Cryo) Blood Product Transfusion | 1 unit | 2 Participants |
p-value: 0.5395% CI: [0.51, 3.79]Regression, Logistic
Primary
Fresh Frozen Plasma (FFP) Blood Product Transfusion
The number of subject's who received 0,1,2,3 or more units of FFP's transfused from completion of study drug administration though midnight of the next day.
Time frame: 24 hours
Population: 1 subject's data was not collected nor analyzed for the FFP arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fresh Frozen Plasma | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 0 units | 43 Participants |
| Fresh Frozen Plasma | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 1 unit | 0 Participants |
| Fresh Frozen Plasma | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 2 units | 4 Participants |
| Fresh Frozen Plasma | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 3 or more units | 1 Participants |
| Prothrombin Complex Concentrate | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 3 or more units | 0 Participants |
| Prothrombin Complex Concentrate | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 0 units | 48 Participants |
| Prothrombin Complex Concentrate | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 2 units | 2 Participants |
| Prothrombin Complex Concentrate | Fresh Frozen Plasma (FFP) Blood Product Transfusion | 1 unit | 1 Participants |
p-value: 0.3995% CI: [0.12, 2.3]Regression, Logistic
Primary
Platelets Blood Product Transfusion
The number of subject's who received 0,1,2,3 or more units of Platelets transfused from completion of study drug administration though midnight of the next day.
Time frame: 24 hours
Population: 1 subject's data was not collected nor analyzed for the FFP arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fresh Frozen Plasma | Platelets Blood Product Transfusion | 0 units | 30 Participants |
| Fresh Frozen Plasma | Platelets Blood Product Transfusion | 1 unit | 13 Participants |
| Fresh Frozen Plasma | Platelets Blood Product Transfusion | 2 units | 3 Participants |
| Fresh Frozen Plasma | Platelets Blood Product Transfusion | 3 or more units | 2 Participants |
| Prothrombin Complex Concentrate | Platelets Blood Product Transfusion | 3 or more units | 3 Participants |
| Prothrombin Complex Concentrate | Platelets Blood Product Transfusion | 0 units | 36 Participants |
| Prothrombin Complex Concentrate | Platelets Blood Product Transfusion | 2 units | 3 Participants |
| Prothrombin Complex Concentrate | Platelets Blood Product Transfusion | 1 unit | 9 Participants |
p-value: 0.5195% CI: [0.33, 1.73]Regression, Logistic
Primary
Red Blood Cell (RBC) Blood Product Transfusion
The number of subject's who received 0,1,2,3 or more units of RBC's transfused from completion of study drug administration though midnight of the next day.
Time frame: 24 hours
Population: 1 subject data was not collected nor analyzed for the FFP arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fresh Frozen Plasma | Red Blood Cell (RBC) Blood Product Transfusion | 0 units | 26 Participants |
| Fresh Frozen Plasma | Red Blood Cell (RBC) Blood Product Transfusion | 1 unit | 11 Participants |
| Fresh Frozen Plasma | Red Blood Cell (RBC) Blood Product Transfusion | 2 units | 6 Participants |
| Fresh Frozen Plasma | Red Blood Cell (RBC) Blood Product Transfusion | 3 or more units | 5 Participants |
| Prothrombin Complex Concentrate | Red Blood Cell (RBC) Blood Product Transfusion | 3 or more units | 2 Participants |
| Prothrombin Complex Concentrate | Red Blood Cell (RBC) Blood Product Transfusion | 0 units | 36 Participants |
| Prothrombin Complex Concentrate | Red Blood Cell (RBC) Blood Product Transfusion | 2 units | 5 Participants |
| Prothrombin Complex Concentrate | Red Blood Cell (RBC) Blood Product Transfusion | 1 unit | 8 Participants |
p-value: 0.0995% CI: [0.22, 1.11]Regression, Logistic