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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01246011
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 9
• Location: 1
• Arms: 3
• Duration (Months): 8
• Patients Per Site Per Month: 1.1

Study Details

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
• 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: Nov 1, 2010
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 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 [Approximately 30 Days post CABG]

   Vein graft patency as measured by computed tomography

Secondary Outcome Measures

1. Major Bleeding Events. [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ik-Kyung Jang, MD, PhD, Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01246011
• Other Study ID Numbers: 2010P001386
• First Posted: Nov 23, 2010
• Last Update Posted: Nov 17, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Warfarin; Argatroban

Study Results

Participant Flow

Recruitment Details	The study began enrolling in January 2011 and screening ended in July 2011, after it was decided that enrollment was too slow and that the study should be terminated.

Arm/Group Title	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)	Heparin PF4 Antibody Positive no Drug	Heparin PF4 Antibody Negative
Arm/Group Description	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication	Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication
Period Title: Overall Study
STARTED	0	0	9
COMPLETED	0	0	5
NOT COMPLETED	0	0	4

Baseline Characteristics

Arm/Group Title	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)	Heparin PF4 Antibody Positive no Drug	Heparin PF4 Antibody Negative	Total
Arm/Group Description	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication	Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication	Total of all reporting groups
Overall Participants	0	0	9	9
Age (Count of Participants)
<=18 years	0 NaN	0 NaN
Between 18 and 65 years	5 Infinity	5 Infinity
>=65 years	4 Infinity	4 Infinity
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (11.3)	61.9 (11.3)
Sex: Female, Male (Count of Participants)
Female	1 Infinity	1 Infinity
Male	8 Infinity	8 Infinity
Region of Enrollment (participants) [Number]
United States	9 Infinity	9 Infinity

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

No analysis will be done due to early study termination

Arm/Group Title	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)	Heparin PF4 Antibody Positive no Drug	Heparin PF4 Antibody Negative
Arm/Group Description	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication	Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication
Measure Participants	0	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

No analysis will be done due to early study termination.

Arm/Group Title	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)	Heparin PF4 Antibody Positive no Drug	Heparin PF4 Antibody Negative
Arm/Group Description	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin 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.	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication	Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication
Measure Participants	0	0	0

Adverse Events

Time Frame	1 month
Adverse Event Reporting Description	1 subject withdrew from the study prior to having a specimen drawn, so there were only 8 participants at risk
Arm/Group Title	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)		Heparin PF4 Antibody Positive no Drug		Heparin PF4 Antibody Negative
Arm/Group Description	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin		Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication		Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication
All Cause Mortality
	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)		Heparin PF4 Antibody Positive no Drug		Heparin PF4 Antibody Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)		Heparin PF4 Antibody Positive no Drug		Heparin PF4 Antibody Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		5/8 (62.5%)
Cardiac disorders
Atrial Fibrillation after Coronary Artery Bypass Surgery	0/0 (NaN)	0	0/0 (NaN)	0	3/8 (37.5%)	3
Bleeding during or immediately after Coronary Artery Bypass Surgery	0/0 (NaN)	0	0/0 (NaN)	0	2/8 (25%)	2
Vascular disorders
Hypotension after Coronary Artery Bypass Graft Surgery	0/0 (NaN)	0	0/0 (NaN)	0	2/8 (25%)	2
Other (Not Including Serious) Adverse Events
	Heparin PF4 Antibody Positive -Drug (Argatroban and Warfarin)		Heparin PF4 Antibody Positive no Drug		Heparin PF4 Antibody Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		5/8 (62.5%)
Cardiac disorders
Low Hematocrit after Coronary Artery Bypass Graft Surgery	0/0 (NaN)	0	0/0 (NaN)	0	4/8 (50%)	4
Pericarditis	0/0 (NaN)	0	0/0 (NaN)	0	1/8 (12.5%)	1
Gastrointestinal disorders
Post operative nausea	0/0 (NaN)	0	0/0 (NaN)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Back spasm	0/0 (NaN)	0	0/0 (NaN)	0	1/8 (12.5%)	1
Nervous system disorders
Parkinson's-like features	0/0 (NaN)	0	0/0 (NaN)	0	1/8 (12.5%)	1
Renal and urinary disorders
Urinary Retention after Coronary Artery Bypass Surgery	0/0 (NaN)	0	0/0 (NaN)	0	1/8 (12.5%)	1

Limitations/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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.