Angiomax in Patients With HIT/HITTS Type II Undergoing CPB

Cardiovascular Disease Clinical Trial

— HIT/TS  

Official title:

A Phase III Study of Angiomax (Bivalirudin) in Patients With HIT/HITTS Type II Undergoing Cardiac Surgery on Cardiopulmonary Bypass (CPB)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00079508
• Other study ID #: TMC-BIV-02-03
• Secondary ID: CHOOSE-On
• Status: Completed
• Phase: Phase 3
• First received: March 9, 2004
• Last updated: November 8, 2011
• Start date: April 2004

Study information

• Verified date: November 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

The purpose of this study is to demonstrate that in patients with heparin-induced thrombocytopenia (HIT)/heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) Type II undergoing cardiac surgery on cardiopulmonary bypass (CPB), Angiomax is a safe and effective anticoagulant.

Description:

An open-label, prospective, multicenter, single-arm study; with a historical reference cohort of similarly identified HIT/HITTS patients from participating institutions that underwent cardiac surgery on CPB with alternative anticoagulation regimens during the period of approximately 12 months prior to initiation of the first patient into this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Provide written informed consent before initiation of any study-related procedures, and

• Be at least 18 years of age, and

• Be scheduled for CABG, CABG single valve surgery, or isolated single valve surgery on CPB. Patients undergoing repeat (redo) CABG are also considered eligible for this study, and demonstrated

• New diagnosis or history of objectively documented HIT/HITTS Type II, defined as one or more of the following:

1. Positive heparin-induced platelet aggregation (HIPA) or other functional assay for HIT or immunoassay for HIT antibodies (ELISA), AND/OR

2. HIT: Thrombocytopenia associated with heparin therapy, where the platelet count has decreased by 50%*, OR

3. HITTS: Thrombocytopenia (as defined in B above) PLUS any evidence of arterial or venous thrombosis

Exclusion Criteria

• Confirmed pregnancy at time of enrollment via IVRS (if woman of child-bearing potential) (Urine or serum pregnancy test)

• Cerebrovascular accident within 6 months, or any cerebrovascular accident with a residual neurological deficit.

• Intracranial neoplasm, arteriovenous malformation or aneurysm.

• Dependency on renal dialysis or creatinine clearance <30mL/min.

• Ongoing treatment with warfarin (or other oral anticoagulant) at the time of enrollment.

Patients previously treated with warfarin may be enrolled if warfarin therapy can be safely discontinued and baseline INR is < 1.3 times control in the absence of heparin therapy.

• Known allergy to Angiomax or hirudin derived drugs, or known sensitivity to any component of the product.

• Patients receiving clopidogrel (Plavix®) within the previous 5 days may be enrolled if in the opinion of the Investigator the benefits of surgery outweigh the risk associated with recent clopidogrel administration.

• Patients receiving a glycoprotein IIb/IIIa inhibitor within the previous 48 hours prior to enrollment if abciximab (ReoPro®) or 12 hours if eptifibatide (Integrilin®) or tirofiban (Aggrastat®), may be enrolled if in the opinion of the Investigator the benefits of surgery outweigh the risk associated with not waiting the 48 or 12 hour time period prior to enrollment.

• Patients receiving lepirudin (Refludan®) or argatroban within the previous 24 hours prior to enrollment.

Patients currently receiving lepirudin or argatroban can be enrolled if they are switched to Angiomax at least 24 hours prior to the planned cardiac surgery.

• Patients receiving LMWH or thrombolytics within the previous 12 hours may be enrolled if in the opinion of the Investigator the benefits of surgery outweigh the risk associated with not waiting the 12 hour time period.

• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment.

• Refusal to undergo blood transfusion should it become necessary.

• Any other disease or condition, which, in the judgment of the Investigator, would place a patient at undue risk by being enrolled in the trial, or cause inability to comply with the trial.

• Planned surgical procedure in which proximal anastomoses will precede distal anastomoses of the bypass grafts.

• Planned (>1) double (or greater) valve repair-replacement (e.g.: AVR-MVR) surgery.

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

• Cardiovascular Disease
• Cardiovascular Diseases
• Coronary Artery Bypass Surgery

Intervention

Drug:
• Angiomax (bivalirudin)
250 mg vial administered as 1.0 mg/kg intravenous (IV) bolus and 2.5 mg/kg/h IV infusion during the procedure with the option to administer additional 0.1 to 0.5 mg/kg boluses to increase the level of anticoagulation as clinically indicated. A low-dose infusion could have been administered in the preoperative phase (up to 48 hours before the procedure) and in the postoperative phase (up to 14 days after the procedure) as clinically indicated for management of HIT/TS. A starting bolus of 0.1 mg/kg and/or an infusion of 0.2 mg/kg/h titrated to a desired activated partial thromboplastin time (aPTT), eg, 1.5-2.5 times baseline aPTT, was recommended.

Locations

Country	Name	City	State
United States	The Cleveland Clinic	Cleveland	Ohio

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	Primary Endpoint	In-hospital acute procedural success, defined as the absence of death, Q wave MI, repeat coronary revascularization, and stroke (hemorrhagic or ischemic) at hospital discharge or Day 7 after surgery ('Day 7/discharge'), whichever occurs first.	7 days	Yes