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

• ClinicalTrials.gov Identifier: NCT01246011
• Recruitment Status: Terminated
• First Posted: November 23, 2010
• Results First Posted: March 12, 2012
• Last Update Posted: November 17, 2017
• Sponsor: Massachusetts General Hospital
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Ik-Kyung Jang, MD, PhD, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Bypass Graft Surgery; Presence of Heparin/Platelet Factor 4 Antibody	Drug: Argatroban and warfarin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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 Start Date: November 2010
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Coronary Artery Bypass Vein Graft Patency [ Time Frame: Approximately 30 Days post CABG ]
   Vein graft patency as measured by computed tomography

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02474

Sponsors and Collaborators

Massachusetts General Hospital

GlaxoSmithKline

Investigators

• Principal Investigator: Ik-Kyung Jang, MD, PhD; Massachusetts General Hospital

More Information

• Responsible Party: Ik-Kyung Jang, MD, PhD, Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01246011
• Other Study ID Numbers: 2010P001386
• First Posted: November 23, 2010
• Results First Posted: March 12, 2012
• Last Update Posted: November 17, 2017
• Last Verified: October 2017

Additional relevant MeSH terms:

Warfarin; Argatroban; Anticoagulants; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors