Pathologic Fibrinolysis
Conditions
Keywords
cardiac surgery, cardiopulmonary bypass, fibrinolysis, thromboelastography, D-Dimers, antifibrinolytic agents
Brief summary
It is common practice to use antifibrinolytic agents before and during cardiopulmonary bypass. They are not without side effects. The investigators want to show that there is no proof of fibrinolysis in standard sternotomy cardiac surgery patients before cardiopulmonary bypass, and that antifibrinolytic agents should only be started on cardiopulmonary bypass.
Detailed description
Double-blind, placebo controlled, prospective study in two groups of 20 patients. Control group (A) receives standard Epsilonaminocaproic acid treatment before cardiopulmonary bypass (10 gr loading dose, and 1 gr/hr infusion), and second group (B) receives placebo. Before start of Epsilonaminocaproic acid/placebo, D-Dimers and Thromboelastography are measured, repeated just before full heparinization. After heparinization group A receives placebo, and group B Epsilonaminocaproic acid.
Interventions
DRUGEpsilonaminocaproic acid
One group receives Epsilonaminocaproic acid, 10 gr IV bolus, followed by 1 gr/hr. Second group receives placebo.
DRUGPlacebo
Placebo administered in same volume as in experimental arm.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All adult patients, undergoing first time sternotomy for Coronary artery bypass grafting/Aortic valve replacement/aortic surgery
Exclusion criteria
* Resternotomy, renal insufficiency, deep hypothermia, age \< 18 yrs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Di-Dimer Increase Before Cardiopulmonary Bypass | 6 months | Change in Di-dimer between preoperative value and value immediately before cardiopulmonary bypass in cardiac surgery patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Value of Thromboelastography as Monitor of Fibrinolysis | 6 months | Thromboelastography may display if fibrinolysis is present |
Other
| Measure | Time frame | Description |
|---|---|---|
| Length of Time Between Incision and Cardiopulmonary Bypass | From incision to bypass, up to 3 hours | Mean Length of Time from Incision to Cardiopulmonary Bypass |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epsilonaminocaproic Acid One arm: Epsilonaminocaproic acid 10 gr IV, followed by 1 gr/hr infusion Second arm: placebo
Epsilonaminocaproic acid: One group receives Epsilonaminocaproic acid, 10 gr IV bolus, followed by 1 gr/hr. Second group receives placebo. | 20 |
| Placebo, Antifibrinolytic Activity Placebo: same IV volume as experimental arm
Placebo: Placebo administered in same volume as in experimental arm. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo, Antifibrinolytic Activity | Total | Epsilonaminocaproic Acid |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 18 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 22 Participants | 12 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 15 | 58 years STANDARD_DEVIATION 16 | 57 years STANDARD_DEVIATION 17 |
| Region of Enrollment United States | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 13 Participants | 23 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Di-Dimer Increase Before Cardiopulmonary Bypass
Change in Di-dimer between preoperative value and value immediately before cardiopulmonary bypass in cardiac surgery patients.
Time frame: 6 months
Population: D-Dimer from preoperative value and value immediately before cardiopulmonary bypass in cardiac surgery patients
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Epsilonaminocaproic Acid | Di-Dimer Increase Before Cardiopulmonary Bypass | Preoperative Value | 317 ng/mL |
| Epsilonaminocaproic Acid | Di-Dimer Increase Before Cardiopulmonary Bypass | Immediately Before Cardiopulmonary Bypass | 317 ng/mL |
| Epsilonaminocaproic Acid | Di-Dimer Increase Before Cardiopulmonary Bypass | Post cardiopulmonary bypass | 537 ng/mL |
| Placebo, Antifibrinolytic Activity | Di-Dimer Increase Before Cardiopulmonary Bypass | Preoperative Value | 266 ng/mL |
| Placebo, Antifibrinolytic Activity | Di-Dimer Increase Before Cardiopulmonary Bypass | Immediately Before Cardiopulmonary Bypass | 291 ng/mL |
| Placebo, Antifibrinolytic Activity | Di-Dimer Increase Before Cardiopulmonary Bypass | Post cardiopulmonary bypass | 911 ng/mL |
Secondary
Value of Thromboelastography as Monitor of Fibrinolysis
Thromboelastography may display if fibrinolysis is present
Time frame: 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Epsilonaminocaproic Acid | Value of Thromboelastography as Monitor of Fibrinolysis | Preoperative Estimated Plasma Lysis | 0 percentage of clot |
| Epsilonaminocaproic Acid | Value of Thromboelastography as Monitor of Fibrinolysis | Estimated Plasma Lysis Prior to Bypass | 0 percentage of clot |
| Epsilonaminocaproic Acid | Value of Thromboelastography as Monitor of Fibrinolysis | Estimated Plasma Lysis Post Bypass | 0 percentage of clot |
| Placebo, Antifibrinolytic Activity | Value of Thromboelastography as Monitor of Fibrinolysis | Preoperative Estimated Plasma Lysis | 0 percentage of clot |
| Placebo, Antifibrinolytic Activity | Value of Thromboelastography as Monitor of Fibrinolysis | Estimated Plasma Lysis Prior to Bypass | 0 percentage of clot |
| Placebo, Antifibrinolytic Activity | Value of Thromboelastography as Monitor of Fibrinolysis | Estimated Plasma Lysis Post Bypass | 0 percentage of clot |
Other Pre-specified
Length of Time Between Incision and Cardiopulmonary Bypass
Mean Length of Time from Incision to Cardiopulmonary Bypass
Time frame: From incision to bypass, up to 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epsilonaminocaproic Acid | Length of Time Between Incision and Cardiopulmonary Bypass | 140 Minutes | Standard Deviation 63 |
| Placebo, Antifibrinolytic Activity | Length of Time Between Incision and Cardiopulmonary Bypass | 165 Minutes | Standard Deviation 63 |
p-value: 0.21t-test, 2 sided