Switching From Fondaparinux to Bivalirudin or Unfractionated Heparin in ACS Patients Undergoing PCI

Study Overview
=================
Brief Summary
-----------------
The primary objective of this clinical trial is to evaluate safety of switching from fondaparinux to either unfractionated heparin or bivalirudin for patients experiencing acute coronary syndrome undergoing percutaneous coronary angioplasty.

Detailed Description
-----------------
This is a prospective open label, randomized, multi-center registry. One hundred patients who received fondaparinux within the 24 hours prior to presentation to the coronary catheterization lab and who are suitable for percutaneous coronary intervention. The patients will be randomized in a 1:1 fashion to either unfractionated heparin or bivalirudin during the angioplasty. All patients will be followed throughout the duration of the hospital stay.

Official Title
-----------------
Switching From Arixtra (Fondaparinux) to Angiomax (Bivalirudin) or Unfractionated Heparin in Patients With Acute Coronary Syndromes (ACS) Without ST-segment Elevation Undergoing Percutaneous Coronary Intervention (PCI): SWITCH III

Conditions
-----------------
Acute Coronary Syndromes

Intervention / Treatment
-----------------
* Drug: Switching from Fondaparinux to Bivalirudin or Unfractionated Heparin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. The patient is, male or female, > 18 years of age; 2. The patient presents with coronary syndrome, unstable angina or non ST segment elevated myocardial infarction (NSTEMI) defined as at least one of the following criteria: Elevated creatine kinase MB or Troponin I or T (above ULN) ECG changes indicative of ischemia 3. The patient is scheduled for angiography, with possible angioplasty, evaluation of their coronary disease; 4. The patient is able and willing to conform to the requirements of the study and voluntarily signs an Informed Consent. ST elevated myocardial infarction within the preceding 48 hours; Patient weighs more than 400 lbs (181.2 kg) or less than 110 lbs (50 kg); Patients presenting on or received bivalirudin, GP IIb/IIIa inhibitors or low-molecular weight heparin within the preceding 24 hours; Patients that received unfractionated heparin less than or equal to 90 minutes prior to fondaparinux administration. Patients with known conditions of bleeding diathesis or actively bleeding within the previous 6 months (GI bleed etc.); Known diagnosis of acute bacterial endocarditis; Patients with cardiogenic shock or required intra-aortic balloon pump (IABP) If patient is on warfarin (Coumadin) therapy; Patients who had a major or minor stroke (CVA or TIA) or major surgery within the past 6 months; Known impaired renal function (creatinine ≥ 3.0 mg/dL (265.2 μmol/L),) status post renal transplant, patients on chronic dialysis or creatinine clearance ≤ 30 ml/min; A platelet count of less than 100,000 cells/mm3; Known allergies to fondaparinux, aspirin, clopidogrel bisulfate (PlavixR), ticlopidine (TiclidR), heparin, bivalirudin, or contrast that cannot be medically managed; Prior angioplasty within the previous 30 days; Contraindication to low-molecular weight heparin, unfractionated heparin or bivalirudin; Pregnant or lactating women; Any significant medical condition, which in the investigator's opinion, may interfere with the patient's optimal participation in the study; Currently participating in an investigational drug or another device study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Heparin<br>Patients are switched from fondaparinux to heparin, receiving a dose of 60 U/Kg IV during the PCI | Drug: Switching from Fondaparinux to Bivalirudin or Unfractionated Heparin<br> <br> |
| Active Comparator: Bivalirudin<br>Patients switched from fondaparinux to bivalirudin, received a bolus of 0.75 mg/kg IV followed by infusion of 1.75 mg/g per hour infusion during the PCI. | Drug: Switching from Fondaparinux to Bivalirudin or Unfractionated Heparin<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge | Characterized as Fatal bleed, Major bleed (SWITCH III criteria) or major bleed (OASIS criteria) | During hospitalization, after Fondaparinux administration, prior to randomization | 
| The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge | Categorized as Fatal bleed, major bleed (SWITCH III criteria) or major bleed (OASIS criteria) | During hospitalization, after randomization, during PCI | 
| The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge | Characterized as fatal bleed, major bleed (SWITCH III criteria) or major bleed (OASIS criteria) | During hospitalization, after PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary in Hospital Endpoint Will be In-hospital Death (Non-hemorrhagic Related), Vascular Access Site Complications, Myocardial Infarction, Need for Repeat Revascularization, Procedural Complication and Catheter Thrombosis | Characterized as death, access site complication, access site thrombus, hematoma, myocardial infarction, repeat vascularization, dissection, stent thrombosis, catheter thrombosis | during index hospitalization |