Comparing Bivalirudin Versus Heparin/ GP IIB/IIA in Patients Undergoing PCI
Recruitment status was: Recruiting
Coronary Artery Disease
Procedure: Percutaneous Coronary Intervention (PCI)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
|Official Title:||Minimizing Post-Procedural Vascular Complications: Comparing Bivalirudin Versus Heparin/GP IIB/IIA in Patients Undergoing Percutaneous Coronary Intervention|
- Number of patients who require a vascular groin ultrasound or abdominal CT.
- Record occurrence of pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, or femoral vein or arterial thrombosis
- Record presence of hematoma and size if applicable.
- Record hemoglobin drop >3g/dl with over bleeding. Also, record any red cell transfusion due to catheterization related bleeding.
- Comparison of time to ambulation.
- Occurrence of major and minor bleeding peri-catheterization.
- Observe incidence of thrombocytopenia post catheterization defined as a platelet count <100,000.
|Study Start Date:||September 2006|
Anti-thrombotic therapies have enhanced the safety of percutaneous coronary intervention (PCI). In addition to aspirin, heparin and platelet glycoprotein (Gp) IIB/IIIA receptor inhibition have been used as the reference strategy to reduce the incidence of ischemic complications during coronary interventions 1. However, the success of this strategy is limited by increased bleeding risk, prolonged drug infusions (12 hours), and patient inconveniences (such as lying flat for hours until blood coagulation becomes normal and sheaths can be safely removed). Peri-procedural bleeding due to vascular complications is one of the most frequent complications of PCI and is associated with adverse events 2.
Newer anti-thrombotic strategies may further improve outcomes after PCI. The efficacy of a direct thrombin inhibitor bivalirudin (Angiomax™) was investigated in a randomized controlled clinical trial as a replacement for the strategy of heparin/Gp IIB/IIIA inhibition in patients undergoing coronary intervention. The REPLACE-2 study, which randomized over 6000 patients found short and long-term clinical outcomes with bivalirudin were as effective as heparin/Gp IIB/IIIA inhibition combination with evidence of significantly less major and minor bleeding 3, 4. This led to approval of the 0.75 mg/kg/1.75 mg/kg/hr dose of Angiomax® by the Food and Drug Administration for use as an anticoagulant in patients with unstable angina undergoing PCI.
It is now routinely accepted that early sheath removal after PCI reduces femoral access site complications and leads to earlier ambulation, earlier discharge, improved patient satisfaction 5. Heparin-based anticoagulation requires monitoring of the coagulation status to determine readiness for sheath removal because of the lack of predictable duration of anticoagulation with heparin. Because clearance of bivalirudin occurs mostly by proteolytic cleavage by thrombin, the drug has more predictable pharmacokinetics and exhibits linear dose relationship with respect to plasma concentrations and coagulation assay endpoints 6. Preliminary studies indicate sheath removal 2 hours after cessation of bivalirudin without coagulation monitoring is safe 5. While REPLACE-2 suggested that catheterization related vascular complications were decreased with bivalirudin, specific data on these endpoints and others such as time to ambulation and time to discharge were not collected because of the blinded nature of the trial. Currently the rate of vascular complications at MGH for patients undergoing PCI is 4.0% which significantly exceeds the national rate of 1.9% (95% CI 1.1 to 3.2) 7.
We will conduct a randomized clinical trial in patients undergoing PCI to compare the rates of vascular related complications between patients assigned to one of two arms: 1) bivalirudin + provisional Gp IIB/IIIA use versus 2) heparin + Gp IIB/IIIA (eptifibatide (Integrilin®)) use. The primary endpoint will be a composite of vascular related groin complications (MAVE-major adverse vascular endpoints as defined in next section). Secondary endpoints will be 1) time to sheath pull; 2) time to ambulation; and 3) occurrence of major and minor bleeding peri-catheterization.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00476944
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Herman K Gold, MD||Massachusetts General Hospital|