Coronary Artery Bypass Graft Surgery, Presence of Heparin/Platelet Factor 4 Antibody
Conditions
Brief summary
Heparin/Platelet Factor 4 (PF4) antibody testing will be performed in subjects who have just undergone coronary artery bypass grafting (CABG) surgery. 30 subjects with a positive antibody result and no signs or symptoms of Heparin Induced Thrombocytopenia (HIT) will be randomized to receive argatroban and warfarin. 30 subjects with a positive antibody result and no signs or symptoms of HIT will be randomized to receive no treatment. 30 subjects with a negative antibody result will also be followed in the study. All subjects will have a cardiac CT scan at about 30 days post surgery to measure the patency of their coronary artery bypass vein grafts. This study will evaluate if treating patients who have heparin PF4 antibodies post-CABG with argatroban and warfarin has any effect on the short-term patency of coronary artery bypass vein grafts.
Detailed description
This is a prospective, randomized, single center study. Patients scheduled for CABG will be screened and enrolled. Subjects positive for heparin/PF4 antibody within 24 h after CABG and without clinical suspicion of HIT will be randomized into one of two groups. An additional 30 patients with negative antibody titers will serve as a control group.
Interventions
DRUGArgatroban and warfarin
Subjects with the presence of heparin PF4 antibodies without signs or symptoms of HIT post CABG will be randomized to receive argatroban and warfarin or no drug for one month.
Sponsors
GlaxoSmithKline
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients scheduled for CABG (males or non-pregnant females) 2. \> 18 years old with at least one vein graft planned 3. Able to provide written informed consent
Exclusion criteria
1. Patients who, in the investigator's or attending surgeon's opinion, are unsuitable for anticoagulation due to their clinical status 2. Documented history of allergy to iodinated contrast media, warfarin, or argatroban 3. Chronic renal impairment with CrCl\<60 ml/min 4. Recent bleeding episode 5. Congestive Heart Failure (EF\< 30%) 6. Bleeding diathesis or known thrombophilic disorder 7. Atrial fibrillation or other condition requiring anticoagulation at the time of enrollment 8. Documented history of heparin induced thrombocytopenia 9. Clinical suspicion of HIT at the time of randomization, defined as 50% decrease in Platelet count from last heparin exposure or Platelet count \<100,000/ml 10. Hepatic dysfunction (defined as LFTs \> 3 times the upper limit of normal) 11. Patients with a history of bleeding complications post-CABG 12. Hemorrhagic stroke 13. Gastrointestinal bleeding 14. Requirement for fresh frozen plasma 15. Recent central nervous system or ophthalmic surgery 16. Aneurysm 17. History of psychosis or senility 18. Malignant hypertension 19. Clinically significant pericarditis or pericardial effusion 20. Bacterial endocarditis 21. Hematocrit \< 24% 22. Valve replacement or repair at time of CABG 23. Subjects with signs or symptoms of possible Transient Ischemic Attack or stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Artery Bypass Vein Graft Patency | Approximately 30 Days post CABG | Vein graft patency as measured by computed tomography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding Events. | At 2weeks post CABG | Intracranial bleed or any clinically overt sign of hemorrhage that is associated with a fall in hemoglobin \> 5 g/dL. |
Countries
United States
Participant flow
Recruitment details
The study began enrolling in January 2011 and screening ended in July 2011, after it was decided that enrollment was too slow and that the study should be terminated.
Participants by arm
| Arm | Count |
|---|---|
| Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin) Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin | 0 |
| Heparin PF4 Antibody Positive no Drug Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication | 0 |
| Heparin PF4 Antibody Negative Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | If needed warfarin clinically, withdrawn | 0 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Heparin PF4 Antibody Negative |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants |
| Age, Continuous | 61.9 years STANDARD_DEVIATION 11.3 | 61.9 years STANDARD_DEVIATION 11.3 |
| Region of Enrollment United States | 9 participants | 9 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 5 / 8 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 5 / 8 |
Outcome results
Primary
Coronary Artery Bypass Vein Graft Patency
Vein graft patency as measured by computed tomography
Time frame: Approximately 30 Days post CABG
Population: No analysis will be done due to early study termination
Secondary
Major Bleeding Events.
Intracranial bleed or any clinically overt sign of hemorrhage that is associated with a fall in hemoglobin \> 5 g/dL.
Time frame: At 2weeks post CABG
Population: No analysis will be done due to early study termination.