Clinical trial NCT01246011: Significance of Antibodies to Heparin/Platelet Factor 4 Complex in Vein Graft Patency and Potential Role of Argatroban for Prevention of Vein Graft Occlusion
Official title: Significance of Antibodies to Heparin/Platelet Factor 4 Complex in Vein Graft Patency and Potential Role of Argatroban for Prevention of Vein Graft Occlusion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Coronary Artery Bypass Graft Surgery
Presence of Heparin/Platelet Factor 4 Antibody
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-11-23
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Coronary Artery Bypass Vein Graft Patency
timeFrame: Approximately 30 Days post CABG
Secondary outcomes:
measure: Major Bleeding Events.
timeFrame: At 2weeks post CABG
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Ik-Kyung Jang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: