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

This study has been terminated.
(Enrollment was too slow.)
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Ik-Kyung Jang, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01246011
First received: November 17, 2010
Last updated: March 9, 2012
Last verified: February 2012
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Coronary Artery Bypass Vein Graft Patency [ Time Frame: Approximately 30 Days post CABG ] [ Designated as safety issue: No ]
    Vein graft patency as measured by computed tomography


Secondary Outcome Measures:
  • Major Bleeding Events. [ Time Frame: At 2weeks post CABG ] [ Designated as safety issue: Yes ]
    Intracranial bleed or any clinically overt sign of hemorrhage that is associated with a fall in hemoglobin > 5 g/dL.


Enrollment: 9
Study Start Date: November 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01246011

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

No publications provided

Responsible Party: Ik-Kyung Jang, MD, PhD, Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01246011     History of Changes
Other Study ID Numbers: 2010P001386
Study First Received: November 17, 2010
Results First Received: January 3, 2012
Last Updated: March 9, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Calcium heparin
Argatroban
Heparin
Warfarin
Platelet Factor 4
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Coagulants
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014