Deep Venous Thrombosis
Conditions
Keywords
Deep venous thrombosis, DVT, Heparin induced thrombocytopenia, HIT, Direct thrombin inhibitor
Brief summary
A blood clot in the veins, also known as deep venous thrombosis (DVT), is one of the most common complications after surgery. This may result in death if a clot breaks off and travel to the lungs; this is referred to as pulmonary embolism (PE). After heart surgery the incidence of DVT ranges from 20-48% and following lung surgery the incidence is 19-26%. In order to decrease the likelihood of this complication, patients receive by injection a blood thinning medicine. Heparin is the usual medicine used for this purpose following heart and lung surgery. Recently there have been reports that other medicines may be more effective than heparin for this purpose. Also there have been reports that some patients develop antibodies to heparin. When this occurs, this may prevent the heparin from being effective and may even promote the formation of blood clots. Antibodies to heparin may be present more often following heart and lung surgery than other types of surgery. There is a new medicine called desirudin (Iprivask), which may be used instead of heparin to prevent blood clots following heart and lung surgery. Desirudin is currently approved by the FDA to prevent blood clots following hip surgery. The purpose of this study is to compare desirudin with heparin for the prevention of vein clots after heart and lung surgery.
Interventions
DRUGDesirudin (Iprivask™)
Patients who are randomized to the desirudin (study) group will receive 15 mg of subcutaneous desirudin twice a day (at 0900 and 2100). These patients will also receive an injection of normal saline placebo at 1300 so that patients in both groups will receive three injections at the same time points.
DRUGHeparin
The patients who are randomized to the Heparin (standard of care) group will receive subcutaneous injections of heparin three times a day (0900, 1300 and 2100).
Sponsors
Barnes-Jewish Hospital
Canyon Pharmaceuticals, Inc.
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are scheduled for elective Cardiac or Thoracic Surgery. * Age \> 18 years of age.
Exclusion criteria
* Patients with a clinical suspicion or a documented history of DVT/PE * Patients who may require anticoagulation during the post-op period. (i.e. Patients with a history of A-fib, scheduled for a MAZE procedure or placement of a mechanical valve, or those on Coumadin/IV heparin preoperatively) * Patients who have a history of HIT or if there is a suspicion of the patient having HIT pre-operatively. * Documented allergy to heparin, desirudin, or lepirudin * Patients with a history of coagulation disorder * Platelet count\< 100 X109 /dl * Active bleeding * Serum Creatinine ≥ 1.5 mg/dl or CrCl ≤ 30 ml/min * Patients with a baseline coagulopathy (INR \> 1.5 or aPTT \> 45 sec) * Patients with liver disease * Pregnancy * Patients who require ventricular assist devices before or after surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure Was the Number of Participants With New Heparin Platelet Factor 4 (HIT Positive) Antibodies in Each Group Within 30 Days Following Surgery. | 30 days after surgery | Blood samples were collected and tested in singlet for the presence of PF4/heparin antibodies. Samples were collected for each participant on PDD (Post-study Drug initiation Day) 2, PDD 7 or at hospital discharge, and at 30 days post surgery. |
Secondary
| Measure | Time frame |
|---|---|
| The Incidence of DVTs in Each Group. | 7 days after surgery |
| The Incidence of Bleeding in Each Group. | Up to 30 days after surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Desirudin Patients randomized to the desirudin group received desirudin 15mg via subcutaneous administration twice daily (0900 and 2100), with saline placebo given once daily at 1300. | 61 |
| Heparin Patients randomized to the heparin group received 5000 units of LDUH via subcutaneous administration three times a day (0900, 1300, and 2100). | 59 |
| Total | 120 |
Baseline characteristics
| Characteristic | Heparin | Desirudin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 23 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 38 Participants | 77 Participants |
| Age, Continuous | 61 years STANDARD_DEVIATION 12 | 62 years STANDARD_DEVIATION 11 | 61 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 59 participants | 61 participants | 120 participants |
| Sex: Female, Male Female | 22 Participants | 26 Participants | 48 Participants |
| Sex: Female, Male Male | 37 Participants | 35 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 61 | 0 / 59 |
| serious Total, serious adverse events | 0 / 61 | 0 / 59 |
Outcome results
Primary
The Primary Outcome Measure Was the Number of Participants With New Heparin Platelet Factor 4 (HIT Positive) Antibodies in Each Group Within 30 Days Following Surgery.
Blood samples were collected and tested in singlet for the presence of PF4/heparin antibodies. Samples were collected for each participant on PDD (Post-study Drug initiation Day) 2, PDD 7 or at hospital discharge, and at 30 days post surgery.
Time frame: 30 days after surgery
Population: Intent-to-treat analysis was performed according to initial group assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Desirudin | The Primary Outcome Measure Was the Number of Participants With New Heparin Platelet Factor 4 (HIT Positive) Antibodies in Each Group Within 30 Days Following Surgery. | 6 participants |
| Heparin | The Primary Outcome Measure Was the Number of Participants With New Heparin Platelet Factor 4 (HIT Positive) Antibodies in Each Group Within 30 Days Following Surgery. | 8 participants |
Comparison: Published data show that the incidence of PF4/heparin EIA antibodies is approximately 40% (range, 20% to 60%) following cardiac surgery. We estimated that antibody formation would occur in approximately 20% of patients following thoracic surgery. Sixty patients in each group would provide 80% power to detect a decrease in the incidence of positive PF4/heparin EIA tests from 20% to 4% at an alpha level of \<0.05.p-value: <0.05Fisher Exact
Secondary
The Incidence of Bleeding in Each Group.
Time frame: Up to 30 days after surgery
Population: Intention to treat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Desirudin | The Incidence of Bleeding in Each Group. | 2 Participants |
| Heparin | The Incidence of Bleeding in Each Group. | 2 Participants |
p-value: <0.05Fisher Exact
Secondary
The Incidence of DVTs in Each Group.
Time frame: 7 days after surgery
Population: 61 in Desirudin group and 59 in heparin group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Desirudin | The Incidence of DVTs in Each Group. | 3 Participants |
| Heparin | The Incidence of DVTs in Each Group. | 2 Participants |
p-value: <0.05Fisher Exact