Blood Coagulation Disorders, Hemorrhage
Conditions
Keywords
Fresh frozen plasma, Bleeding
Brief summary
The purpose of this study is to evaluate prophylactic fresh frozen plasma transfusion in patients with moderately elevated international normalized ratios (INR) prior to undergoing an invasive procedure.
Detailed description
Fresh frozen plasma is used very frequently in the US. Many plasma transfusions are given prior to a procedure in order to correct perceived bleeding risk, yet there is little evidence to support that use of plasma reduces bleeding. There has never been an adequately powered trial to establish the efficacy of plasma and document the risks. This pilot study will evaluate the feasibility of conducting a research protocol that will lead to a large scale clinical trial designed to evaluate the treatment effectiveness of prophylactic plasma transfusion in patients with moderately elevated INRs prior to undergoing an invasive procedure outside of the operating room. Study subjects will be randomly allocated to either receive either plasma transfusion prior to the procedure, or to no treatment. Study outcomes will be compared between the two study arms. Recruitment rates, protocol adherence, and rates of study outcomes will be assessed to determine the feasibility of the large scale trial.
Interventions
BIOLOGICALFresh frozen plasma transfusion
Pre-procedure fresh frozen plasma transfusion (15 cc per Kg to a maximum of 5 units)
Sponsors
Rutgers, The State University of New Jersey
University of Pittsburgh
Johns Hopkins University
University of Washington
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. INR level between 1.50 and 2.50 inclusive 2. undergoing an invasive procedure at the bedside, endoscopy laboratory, or in radiology
Exclusion criteria
1. undergoing a surgical procedure in the operating room; 2. active bleeding; 3. undergoing a procedure involving or proximal to the central nervous system or spinal cord; 4. cardiac catheterization, 5. using 4 factor plasma concentrates 6. using systemic heparin/heparinoid therapy, direct factor X inhibitors and other anticoagulants for which plasma will not correct prolonged INR; 7. platelet count less than 50,000/ul, 8. congenital coagulation disorders; 9. acquired disorders (i.e., lupus anticoagulant) for which plasma will not correct the disorder; 10. women who are pregnant and; 11. unwillingness to consider blood transfusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Level | within 2 days post procedure | Change from pre-procedure hemoglobin to lowest within 2 days after procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Transfusion Associated Cardiac Overload (TACO) | within 2 days post procedure | Difference in rates between the two study arms |
| Number of Participants With Transfusion Related Acute Lung Injury (TRALI). | with 2 days post procedure | Difference in rates between the two study arms |
| Number of Participants With Major Bleed | with 2 days post procedure | 2g/dL or greater fall in hemoglobin level |
| Change in International Normalized Ratio (INR) Level Post Procedure | day of procedure | Change from pre-procedure INR level |
| Number of Red Blood Cell Transfusions | within 2 days post procedure | Differences in number of units of red blood cell transfusions between the two study arms |
| Change in INR Level Day 2 | day 2 post procedure | Change from pre-procedure INR level |
| Mortality (Number of Participants) | in-hospital up to 7 days | Death |
| Number of Participants With Infection | within 2 days post procedure | Pneumonia or blood stream infection |
| Number of Participants With ICU Admission | within 2 days post procedure | new admission to the intensive care unit |
| Change in INR Level Day 1 | day 1 post procedure | Change from pre-procedure INR level |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fresh Frozen Plasma Transfusion Pre-procedure fresh frozen plasma transfusion (15 cc per Kg, range 10-20 cc/Kg, to a maximum of 5 units)
Fresh frozen plasma transfusion: Pre-procedure fresh frozen plasma transfusion (15 cc per Kg to a maximum of 5 units) | 27 |
| No Transfusion No transfusions prior to the procedure | 30 |
| Total | 57 |
Baseline characteristics
| Characteristic | Fresh Frozen Plasma Transfusion | Total | No Transfusion |
|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 18 | 56.0 years STANDARD_DEVIATION 16 | 58.2 years STANDARD_DEVIATION 13.9 |
| Chronic Obstructive Pulmonary Disease (COPD) | 1 Participants | 4 Participants | 3 Participants |
| Congestive heart failure | 3 Participants | 12 Participants | 9 Participants |
| Coronary artery disease | 4 Participants | 11 Participants | 7 Participants |
| Diabetes | 10 Participants | 24 Participants | 14 Participants |
| Hypertension | 14 Participants | 33 Participants | 19 Participants |
| Liver disease | 15 Participants | 37 Participants | 22 Participants |
| Metastatic carcinoma | 2 Participants | 5 Participants | 3 Participants |
| Prior history of bleeding | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 45 Participants | 23 Participants |
| Region of Enrollment United States | 27 participants | 57 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 16 Participants | 37 Participants | 21 Participants |
| Thromboembolism | 4 Participants | 5 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 27 | 0 / 30 |
| other Total, other adverse events | 0 / 27 | 0 / 30 |
| serious Total, serious adverse events | 2 / 27 | 3 / 30 |
Outcome results
Primary
Change in Hemoglobin Level
Change from pre-procedure hemoglobin to lowest within 2 days after procedure
Time frame: within 2 days post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fresh Frozen Plasma Transfusion | Change in Hemoglobin Level | -0.6 g/dL | Standard Deviation 1 |
| No Transfusion | Change in Hemoglobin Level | -0.4 g/dL | Standard Deviation 0.6 |
Secondary
Change in INR Level Day 1
Change from pre-procedure INR level
Time frame: day 1 post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fresh Frozen Plasma Transfusion | Change in INR Level Day 1 | -0.22 ratio | Standard Deviation 0.19 |
| No Transfusion | Change in INR Level Day 1 | -0.03 ratio | Standard Deviation 0.19 |
Secondary
Change in INR Level Day 2
Change from pre-procedure INR level
Time frame: day 2 post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fresh Frozen Plasma Transfusion | Change in INR Level Day 2 | -0.09 ratio | Standard Deviation 0.39 |
| No Transfusion | Change in INR Level Day 2 | 0 ratio | Standard Deviation 0.19 |
Secondary
Change in International Normalized Ratio (INR) Level Post Procedure
Change from pre-procedure INR level
Time frame: day of procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fresh Frozen Plasma Transfusion | Change in International Normalized Ratio (INR) Level Post Procedure | -0.24 ratio | Standard Deviation 0.26 |
| No Transfusion | Change in International Normalized Ratio (INR) Level Post Procedure | 0 ratio | Standard Deviation 0.15 |
Secondary
Mortality (Number of Participants)
Death
Time frame: in-hospital up to 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fresh Frozen Plasma Transfusion | Mortality (Number of Participants) | 1 Participants |
| No Transfusion | Mortality (Number of Participants) | 0 Participants |
Secondary
Number of Participants With ICU Admission
new admission to the intensive care unit
Time frame: within 2 days post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fresh Frozen Plasma Transfusion | Number of Participants With ICU Admission | 1 Participants |
| No Transfusion | Number of Participants With ICU Admission | 2 Participants |
Secondary
Number of Participants With Infection
Pneumonia or blood stream infection
Time frame: within 2 days post procedure
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fresh Frozen Plasma Transfusion | Number of Participants With Infection | Pneumonia | 0 Participants |
| Fresh Frozen Plasma Transfusion | Number of Participants With Infection | Blood stream infection | 2 Participants |
| No Transfusion | Number of Participants With Infection | Pneumonia | 1 Participants |
| No Transfusion | Number of Participants With Infection | Blood stream infection | 1 Participants |
Secondary
Number of Participants With Major Bleed
2g/dL or greater fall in hemoglobin level
Time frame: with 2 days post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fresh Frozen Plasma Transfusion | Number of Participants With Major Bleed | 1 Participants |
| No Transfusion | Number of Participants With Major Bleed | 0 Participants |
Secondary
Number of Participants With Transfusion Associated Cardiac Overload (TACO)
Difference in rates between the two study arms
Time frame: within 2 days post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fresh Frozen Plasma Transfusion | Number of Participants With Transfusion Associated Cardiac Overload (TACO) | 0 Participants |
| No Transfusion | Number of Participants With Transfusion Associated Cardiac Overload (TACO) | 2 Participants |
Secondary
Number of Participants With Transfusion Related Acute Lung Injury (TRALI).
Difference in rates between the two study arms
Time frame: with 2 days post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fresh Frozen Plasma Transfusion | Number of Participants With Transfusion Related Acute Lung Injury (TRALI). | 0 Participants |
| No Transfusion | Number of Participants With Transfusion Related Acute Lung Injury (TRALI). | 0 Participants |
Secondary
Number of Red Blood Cell Transfusions
Differences in number of units of red blood cell transfusions between the two study arms
Time frame: within 2 days post procedure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fresh Frozen Plasma Transfusion | Number of Red Blood Cell Transfusions | 0 units |
| No Transfusion | Number of Red Blood Cell Transfusions | 0 units |