Anticoagulant Therapy With Bivalirudin in the Performance of Percutaneous Coronary Intervention in Patients With Heparin-Induced Thrombocytopenia (AT BAT, First Inning)

Thrombosis Clinical Trial

Official title:

Anticoagulant Therapy With Bivalirudin in the Performance of PCI in Patients With Heparin-Induced Thrombocytopenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00043940
• Other study ID #: TMC-98-10
• Status: Completed
• Phase: Phase 3
• First received: August 14, 2002
• Last updated: September 15, 2011
• Start date: April 1999

Study information

• Verified date: September 2011
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To assess the safety of bivalirudin as an alternative anticoagulant therapy for patients with new or previous heparin-induced thrombocytopenia (HIT) / heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) undergoing percutaneous coronary intervention (PCI). This will be measured by the composite incidence of major bleeding events during administration or within 48 hours after stopping bivalirudin (or at hospital discharge, whichever occurs first). The components of the composite endpoint are: a) intracranial bleeding; b) retroperitoneal bleeding; c) bleeding that results in hemodynamic compromise; d) bleeding that requires transfusion of three or more units of whole blood or packed red cells; and e) a decrease in hemoglobin of greater than or equal to g/dL or in hematocrit of greater than or equal to 9%.

Secondary Objectives:

Each component of the primary composite endpoint.

To evaluate the level of anticoagulation achieved with bivalirudin. The goal is to achieve an activated clotting time (ACT) between 300 and 350 sec during PCI and 4-hour bivalirudin infusion.

To evaluate bivalirudin's effects on platelet counts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. primary completion date: February 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

INCLUSION:

• Males and females at least 18 years of age,

• Be able to provide written informed consent,

• Need anticoagulation for percutaneous coronary intervention (angioplasty, rotational atherectomy, directional coronary atherectomy, transluminal extraction catheter, or coronary stent),

• New diagnosis or history of clinically suspected or objectively documented HIT/HITTS, defined as:

(A) Positive heparin-induced platelet aggregation (HIPA) or other functional assay, defined as: (B) HIT: Thrombocytopenia associated with heparin therapy, where the platelet count: (i) has decreased to <100x10(9)/L (minimum of 30% drop from the platelet count before heparin treatment), OR (ii) has decreased to <150x10(9)/L (minimum of 40% drop from the platelet count before heparin treatment, OR, (C) HITTS: Thrombocytopenia (as defined above) PLUS arterial or venous thrombosis (deep-vein thrombosis, pulmonary embolism, mesenteric venous or arterial thrombosis, acute myocardial infarction, left ventricular thrombus, ischemic stroke, or occlusion or limb arteries), diagnosed by physical exam/lab evidence and/or appropriate imaging studies (duplex ultrasound, venography, ventilation-perfusion scan, venous or arterial angiography, MRI/MRA, catheterization).

EXCLUSION:

• Overt or known active significant bleeding,

• Definitive evidence of an alternative explanation for the thrombocytopenia (e.g.m DIC, sepsis, other consumptive coagulopathy, ITP, TTP, HUS, or bone-marrow failure),

• Coagulation disorder or bleeding diathesis unrelated to HIT/HITTS,

• Patients with renal impairment, defined as calculated creatinine clearance <30 mL/min, or any other medical conditions (including hepatic, pulmonary, gastrointestinal, endocrine, or psychiatric) that, in the investigator's opinion, would endanger the patient if she/he receives anticoagulant therapy,

• Nonhemorrhagic stroke within the past 6 months or any previous hemorrhagic stroke,

• Intracranial neoplasm, or cerebral/spinal arteriovenous malformation or aneurysm,

• Lumbar puncture, or spinal/epidural catheter placement within the past 7 days,

• Known prior hemorrhage (gastrointestinal, genitourinary, pericardia, pleural, retroperitoneal spaces), major surgery, or serious trauma within the past 6 weeks, unless attending physician believes the need for anticoagulation with PCI outweighs the potential bleeding risk,

• Puncture of a non-compressible vessel within 24 hours before the planned PCI,

• Confirmed uncontrolled hypertension (systolic blood pressure > or = 100 mmHg) at study entry,

• Ongoing anticoagulant therapy at study entry. However, patients may be entered if the therapy can be safely stopped periprocedurally, or, in the case of oral warfarin, if the prothrombin time INR can safely be brought to < or = 1.5 just before study drug infusion,

• Known or suspected pregnancy, or breast-feed. Women of childbearing potential must have a negative pregnancy test (urine or blood) and must be made explicitly aware that bivalirudin may cause excessive menstrual bleeding. Known or suspected pregnancy, or breast-feeding,

• Known hypersensitivity to bivalirudin or leech proteins,

• If the patient has participated in a drug trial within the past 48 hour, call the DCRI hotline.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heparin-Induced Thrombocytopenia
• Thrombocytopenia
• Thrombocytosis
• Thrombosis

Intervention

Drug:
• bivalirudin
Bivalirudin therapy will be given as a 0.75-mg/kg intravenous bolus and 1.75-mg/kg/h intravenous infusion during procedure and up to 4 hours.

Locations

Country	Name	City	State
United States	Duke Clinical Research Institute, Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major bleeding events	composite incidence of major bleeding events during administration or within 48 hours after stopping bivalirudin	48 hours	Yes