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

NCT01246011 | Terminated Phase 4 Results DMC

• 1 other identifier: 2010P001386
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Bypass Graft Surgery; Presence of Heparin/Platelet Factor 4 Antibody

Outcome Measures

Primary Outcomes (1)

• Coronary Artery Bypass Vein Graft Patency

  Vein graft patency as measured by computed tomography

  Approximately 30 Days post CABG

Secondary Outcomes (1)

• Major Bleeding Events.

  At 2weeks post CABG

Study Arms (3)

Heparin PF4 antibody positive -Drug (argatroban and warfarin)

EXPERIMENTAL

Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin

Drug: Argatroban and warfarin

Heparin PF4 antibody positive no drug

NO INTERVENTION

Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication

Heparin PF4 antibody negative

NO INTERVENTION

Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication

Interventions

Argatroban and warfarin DRUG

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.

Heparin PF4 antibody positive -Drug (argatroban and warfarin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled for CABG (males or non-pregnant females)
• \> 18 years old with at least one vein graft planned
• Able to provide written informed consent

You may not qualify if:

• Patients who, in the investigator's or attending surgeon's opinion, are unsuitable for anticoagulation due to their clinical status
• Documented history of allergy to iodinated contrast media, warfarin, or argatroban
• Chronic renal impairment with CrCl\<60 ml/min
• Recent bleeding episode
• Congestive Heart Failure (EF\< 30%)
• Bleeding diathesis or known thrombophilic disorder
• Atrial fibrillation or other condition requiring anticoagulation at the time of enrollment
• Documented history of heparin induced thrombocytopenia
• 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
• Hepatic dysfunction (defined as LFTs \> 3 times the upper limit of normal)
• Patients with a history of bleeding complications post-CABG
• Hemorrhagic stroke
• Gastrointestinal bleeding
• Requirement for fresh frozen plasma
• Recent central nervous system or ophthalmic surgery

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02474, United States

Location

MeSH Terms

Interventions

argatroban; Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study was ended early due to slow enrollment and results will not be analyzed. The 4 subjects who completed the study were all in the same arm of the study.

Results Point of Contact

• Title: Anne Philip, Data Manager
• Organization: Massachusetts General Hospital

alphilip@partners.org

617 726 0423

Study Officials

• Ik-Kyung Jang, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 23, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: November 17, 2017
• Results First Posted: March 12, 2012

Record last verified: 2017-10

Locations

US (1)