Significance of Antibodies to Heparin/Platelet Factor 4 Complex in Vein Graft Patency and Potential Role of Argatroban for Prevention of Vein Graft Occlusion

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.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Bypass Graft Surgery; Presence of Heparin/Platelet Factor 4 Antibody
• Intervention / Treatment: Drug: Argatroban and warfarin

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02474
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Argatroban 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.
No Intervention: Heparin PF4 antibody positive no drug; Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication
No Intervention: Heparin PF4 antibody negative; Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Artery Bypass Vein Graft Patency	Vein graft patency as measured by computed tomography	Approximately 30 Days post CABG

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Bleeding Events.	Intracranial bleed or any clinically overt sign of hemorrhage that is associated with a fall in hemoglobin > 5 g/dL.	At 2weeks post CABG

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 19, 2010
• First Posted (Estimate): November 23, 2010

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Warfarin; Argatroban
• Other Study ID Numbers: 2010P001386