Clinical trial NCT00079508: Angiomax in Patients With HIT/HITTS Type II Undergoing CPB
Official title: A Phase III Study of Angiomax (Bivalirudin) in Patients With HIT/HITTS Type II Undergoing Cardiac Surgery on Cardiopulmonary Bypass (CPB)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Disease
Coronary Artery Bypass Surgery
Keywords: Heparin-induced Thrombocytopenia
Heparin-induced Thrombocytopenia/Thrombosis Syndrome
HIT/HITTS
Heparin anti-body positive
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2004-03-11
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: An open-label, prospective, multicenter, single-arm study; with a historical reference cohort of similarly identified HIT/HITTS patients from participating institutions that underwent cardiac surgery on CPB with alternative anticoagulation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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary Endpoint
timeFrame: 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Medicines Company
name: Malcolm Lloyd, MD
role: STUDY_DIRECTOR
References: