Bridging Therapy in Patients at High Risk for Stent Thrombosis Undergoing Surgery

• ClinicalTrials.gov Identifier: NCT00653601
• Recruitment Status: Unknown
• First Posted: April 7, 2008
• Last Update Posted: September 4, 2009
• Sponsor: Cedars-Sinai Medical Center
• Information provided by: Cedars-Sinai Medical Center

Study Description

Brief Summary:

Patients who have undergone placement of coronary stents require dual antiplatelet therapy with Plavix and aspirin to prevent the serious complication of in-stent thrombosis. Some of these patients will require surgery while on dual antiplatelet therapy. This poses a challenge because being on Plavix is associated with higher risks of perioperative bleeding, but stopping Plavix puts patients at increased risk for in-stent thrombosis.

Currently, the ACC/AHA guidelines recommend discontinuation of Plavix five days prior to surgery to prevent bleeding complications. However, there are no universal recommendations for preventing in-stent thrombosis. Some experts recommend the use glycoprotein IIb/IIIa inhibitors (short-acting antiplatelet agents) as "bridging therapy" during the high-risk perioperative period. Although these agents should be beneficial based on theory, there is currently no published data on their effectiveness for this purpose.

The current study proposes to evaluate the value of Aggrastat (a short-acting intravenous platelet glycoprotein IIb/IIIa inhibitor) in decreasing the risk of in-stent thrombosis without increasing the risk of perioperative bleeding.

Condition or disease
Bleeding; Thrombosis

Detailed Description:

A. D/C clopidogrel 5 days prior to surgery

B. Continue ASA (Increase dose to 325 mg until prohibitive bleeding risk)

C. Check baseline IIb/IIIa and P2Y12 via the Verify Now device prior to initiating tirofiban

D. Start Tirofiban 2 days prior to the procedure (Patient MUST be on a monitored bed)

• Load Tirofiban ONLY if P2Y12 (Verify Now Assay) platelet inhibition is < 20% OTHERWISE initiate only the continuous infusion dose
• Creatinine clearance > 30mL/min: Tirofiban 0.4 mcg/kg/min for 30 minutes, followed by continuous infusion at 0.1 mcg/kg/min
• Creatinine clearance < 30mL/min: Tirofiban 0.2 mcg/kg/min for 30 minutes, followed by continuous infusion of 0.05 mcg/kg/min

E. Check steady state IIb/IIIa inhibitor verify now assay (>8 hour after initiation)

F. Hold Tirofiban 12 hours prior to procedure

G. Check IIb/IIIa inhibitor verify now assay (10-12 hours after Tirofiban is discontinued)

H. CBC pre and post op

I. Reload clopidogrel> 24 hours post op (300 mg X 1 then 75 mg daily) unless prohibitive bleeding risk

J. Reduce ASA to pre-procedure dose. Restart ASA, 24 hours port-op if it was D/C prior to procedure

K. Check P2Y12 via the Verify Now device post-loading dose of clopidogrel (test cannot be performed w/in 48 hours of the D/C of IIb/IIIa inhibitor (tirofiban)

Study Design

• Study Type: Observational
• Estimated Enrollment: 20 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Bridging Therapy in Patients at High Risk for Stent Thrombosis Undergoing Surgery
• Study Start Date: April 2008
• Estimated Primary Completion Date: April 2011
• Estimated Study Completion Date: April 2011

Groups and Cohorts

Group/Cohort
1; Patients who receive bridge therapy with tirofiban who were previously on plavix for drug eluting or bare metal stent prior to scheduled invasive procedures
2; Patients who do NOT receive bridge therapy previously on plavix for drug eluting or bare metal stent prior to scheduled invasive procedures. This will entail of a matching case-control for the following characteristics.; # of RF for stent thrombosis; types of stents; time frame when the stents were placed; procedure type

Outcome Measures

Primary Outcome Measures :

1. In-stent thrombosis as assessed by acute coronary syndromes of unstable angina/non-ST elevation myocardial infarction or ST-elevation myocardial infarction during the hospitalization. [ Time Frame: until discharge ]

Secondary Outcome Measures :

1. Platelet function using the Verify Now device: T1 - at admission (2-3 days after the D/C of Plavix and prior to initiation of Aggrastat infusion); T2 - > 8 hours after initiation of Aggrastat; T3 - pre-operative; T4 - post loading dose of clopidogrel. [ Time Frame: until discharge ]
2. Bleeding as assessed by hematocrit values obtained immediately pre-operative, immediately post-operative, and prior to discharge In addition, the use of blood products (pRBCs, platelets, FFP) will be assessed. [ Time Frame: until discharge ]

Biospecimen Retention:   Samples Without DNA

2 mL of blood for testing X 5 per patient

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients' with BMS/DES on plavix prior to surgery who are in need of an elective procedures

Criteria

Inclusion Criteria:

• Patients' with BMS/DES on plavix prior to surgery who are in need of an elective procedures

Exclusion Criteria:

• Patients' with BMS/DES on NOT plavix prior to surgery who are in need of an elective procedures

Contacts and Locations

Locations

United States, California

Cedars-Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Contact: Sanjay Kaul, MD 310-423-4876 sanjay.kaul@cshs.org

Contact: Suhail Dohad, MD 310-278-3400 dohad@cvmg.com

Principal Investigator: Sanjay Kaul, MD

Sub-Investigator: Amanda B Lamer, PharmD

Sub-Investigator: Hai Tran, PharmD

Sub-Investigator: Stanley Chou, MD

Sub-Investigator: Suhail Dohad, MD

Sponsors and Collaborators

Cedars-Sinai Medical Center

Investigators

• Principal Investigator: Sanjay Kaul, MD; Attending physician

More Information

• Responsible Party: Dr Sanjay Kaul, PI, CSMC
• ClinicalTrials.gov Identifier: NCT00653601
• Other Study ID Numbers: Pro00014008
• First Posted: April 7, 2008
• Last Update Posted: September 4, 2009
• Last Verified: September 2009

Keywords provided by Cedars-Sinai Medical Center:

GPI; glycoprotein IIb/IIIa inhibitor; Aggrastat; Tirofiban; Verify now; platelet function testing; bridge therapy

Additional relevant MeSH terms:

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases