Comparing Bivalirudin Versus Heparin/ GP IIB/IIA in Patients Undergoing PCI

May 18, 2007 updated by: Gold, Herman K., MD

Minimizing Post-Procedural Vascular Complications: Comparing Bivalirudin Versus Heparin/GP IIB/IIA in Patients Undergoing Percutaneous Coronary Intervention

The purpose of this study is to compare the rates of vascular related complications in patients undergoing percutaneous coronary intervention assigned to one of two arms: 1) bivalirudin + provisional Gp IIB/IIIA use versus 2) heparin + Gp IIB/IIIA (eptifibatide (Integrilin®)) use.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Herman K Gold, MD
        • Sub-Investigator:
          • Aloke V Finn, MD
        • Sub-Investigator:
          • Igor F Palacios, MD
        • Sub-Investigator:
          • Robert C. Leinbach, MD
        • Sub-Investigator:
          • Kenneth Rosenfield, MD
        • Sub-Investigator:
          • Joseph Garasic, MD
        • Sub-Investigator:
          • Eugene Pomerantsev, MD, PhD
        • Sub-Investigator:
          • Ignacio Inglessis, MD
        • Sub-Investigator:
          • Farouc A Jaffer, MD, PhD
        • Sub-Investigator:
          • Andrew Maree, MD
        • Sub-Investigator:
          • George T Lau, MD
        • Sub-Investigator:
          • Owen C Raffel, MD
        • Sub-Investigator:
          • Leon M Ptaszek, MD
        • Sub-Investigator:
          • Vishal Gupta, MD
        • Sub-Investigator:
          • Maureen Daher, RN
        • Sub-Investigator:
          • Jae S Oh, BSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients must meet ALL of the following criteria:

  • The patients must be >18 years of age
  • Patients must have been referred for percutaneous coronary intervention (PCI)
  • Diagnosis of angina pectoris defined by Canadian Cardiovascular Society Classification (CCS I, II, III, IV) OR unstable angina pectoris (Braunwald Classification B&C, I-II-III) OR patients with documented silent ischemia;
  • Treatment of lesions in native coronary vessels or bypass grafts requiring angioplasty or stenting.
  • Patient is willing to comply with the specified follow-up evaluation;
  • Patient must provide written informed consent prior to the procedure using a form that is approved by the local Institutional Review Board.

Exclusion Criteria:

Patients will be excluded if ANY of the following conditions apply:

  • Patient has experienced an ST-segment elevation myocardial infarction within the preceding 24 hours.
  • Active internal bleeding or bleeding diathesis, surgery, trauma, or gastrointestinal or genitourinary tract bleeding within past 6 weeks; prior intracranial bleeding; or platelet count<100,000
  • Woman of child-bearing potential unless demonstrated negative pregnancy test
  • End Stage Renal Disease requiring hemodialysis
  • Recipient of heart transplant;
  • Current treatment with 1) intravenous unfractionated heparin or treatment with low molecular weight heparin within past 8 hours; 2)bivalirudin; 3)abciximab; 4)eptifibatide; or tirofiban
  • Ongoing need for warfarin or heparin therapy
  • Known allergies to aspirin, clopidogrel bisulfate (Plavix®) and/or heparin;
  • 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;
  • Any contraindication to glycoprotein IIb/IIIa inhibitor (eptifibatide (Integrilin®)) or bivalirudin therapy;
  • Chronic or relapse/remitting hemolytic condition or pre-catheterization hematocrit<30 mg/dl
  • Unprotected left main coronary disease with >50% stenosis;
  • Platelet count <150,000

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.

Secondary Outcome Measures

Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gold, Herman K., MD

Collaborators

The Medicines Company

Investigators

  • Principal Investigator: Herman K Gold, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Study Registration Dates

First Submitted

May 18, 2007

First Submitted That Met QC Criteria

May 18, 2007

First Posted (Estimate)

May 22, 2007

Study Record Updates

Last Update Posted (Estimate)

May 22, 2007

Last Update Submitted That Met QC Criteria

May 18, 2007

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006P000944

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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