Ignite Creation Date:
2024-05-05 @ 5:17 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00421252
Status:
TERMINATED
Last Update Posted:
2017-04-14
First Post:
2007-01-10
Brief Title:
Role of Plavix in Hemorrhagic and Ischemic Complications of Catheterization
Sponsor:
Beth Israel Deaconess Medical Center
Organization:
Beth Israel Deaconess Medical Center
Study Overview
Official Title:
Impact of Pre-treatment With 600mg of Clopidogrel Plavix on the Incidence of Ischemic and Hemorrhagic Complications in Patients Undergoing Elective Percutaneous Coronary Revascularization--Prospective Randomized Trial
Status:
TERMINATED
Status Verified Date:
2017-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Difficult to enroll patients limited resources available
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients who have stents placed in their coronary arteries require treatment with at least two medications to prevent platelets from sticking to the stainless steel stent and forming a blood clot that can result in a heart attack The 2 anti-platelet medications used for most patients with stents are aspirin and clopidogrel Plavix These are usually prescribed for 1-12 months the length of time depends on the number and types of stents implanted Although the typical long-term dose of clopidogrel is 75 mg by mouth once daily a larger dose known as a loading dose is usually given at the start of treatment to help the medication take effect more quickly
Prior to January 2006 most patients at the Beth Israel Deaconess Medical Center BIDMC who were undergoing PCI and who had not already been taking clopidogrel would receive a loading dose of 300-600 mg of clopidogrel in the cardiac catheterization procedure room immediately after the angioplasty and stenting portion of the procedure However several recent studies suggest that administering clopidogrel 600 mg at least two hours prior to an angioplasty procedure can reduce the rate of complications afterwards especially reducing the chances of detectable damage to the heart muscle
The main purpose of this study is to see whether giving a loading dose of clopidogrel 600 mg to outpatients scheduled to undergo cardiac catheterization with coronary angiography can decrease the risk of procedure-related complications during the 14 days following the cardiac catheterization compared to a strategy of giving clopidogrel 600 mg after the procedure only to those who undergo angioplasty We will focus our attention particularly on detecting damage to heart muscle following angioplasty which might be expected to improve with a loading dose of clopidogrel before the procedure and on bleeding and other groin complications which might worsen with clopidogrel loading before the procedure
The drug clopidogrel has been approved by the Food and Drug Administration FDA for use in patients with a recent or ongoing heart attack narrowings in major blood vessels outside the heart or recent stroke with a loading dose of 300 mg followed by 75 mg once daily It has been used in several large studies with a loading dose of 600 mg without a significant increase in major adverse effects However we do not yet know if it is useful or safe when given as a loading dose of 600 mg before cardiac catheterization for outpatients with stable symptoms and who are not thought to be in the midst of a heart attack
Prior to January 2006 most patients at the Beth Israel Deaconess Medical Center BIDMC who were undergoing PCI and who had not already been taking clopidogrel would receive a loading dose of 300-600 mg of clopidogrel in the cardiac catheterization procedure room immediately after the angioplasty and stenting portion of the procedure However several recent studies suggest that administering clopidogrel 600 mg at least two hours prior to an angioplasty procedure can reduce the rate of complications afterwards especially reducing the chances of detectable damage to the heart muscle
The main purpose of this study is to see whether giving a loading dose of clopidogrel 600 mg to outpatients scheduled to undergo cardiac catheterization with coronary angiography can decrease the risk of procedure-related complications during the 14 days following the cardiac catheterization compared to a strategy of giving clopidogrel 600 mg after the procedure only to those who undergo angioplasty We will focus our attention particularly on detecting damage to heart muscle following angioplasty which might be expected to improve with a loading dose of clopidogrel before the procedure and on bleeding and other groin complications which might worsen with clopidogrel loading before the procedure
The drug clopidogrel has been approved by the Food and Drug Administration FDA for use in patients with a recent or ongoing heart attack narrowings in major blood vessels outside the heart or recent stroke with a loading dose of 300 mg followed by 75 mg once daily It has been used in several large studies with a loading dose of 600 mg without a significant increase in major adverse effects However we do not yet know if it is useful or safe when given as a loading dose of 600 mg before cardiac catheterization for outpatients with stable symptoms and who are not thought to be in the midst of a heart attack
Detailed Description:
SIGNIFICANCE AND BACKGROUND FOR THE STUDY The benefits of dual anti-platelet therapy with full dose aspirin and a thienopyridine have been firmly established in patients undergoing coronary stenting Leon showed reduction in the combined end-point of death myocardial infarction target vessel revascularization and stent thrombosis from 35 with aspirin alone to 23 with aspirin and ticlopidine This benefit was associated however with an increased rate of bleeding and vascular complications of 55 with aspirinticlopidine versus 18 with aspirin alone Multiple other studies have evaluated the safety and efficacy of the thienopyridine clopidogrel in percutaneous coronary intervention PCI In patients at intermediate risk without elevation of troponin-T prior to PCI pretreatment with clopidogrel several hours before the procedure reduced the event rate and obviated the need for additional glycoprotein IIbIIIa receptor inhibition ISAR-REACT In the Clopidogrel for the Reduction of Events During Observation CREDO Study investigators showed that the benefit of pretreatment with 300 mg of clopidogrel was only seen when the pretreatment was instituted at least 12 hours pre-procedure optimally 24 hours before the PCI However survival analysis in this study showed a cumulative event rate at 30 days of 83 in the placebo arm 78 in those administered clopidogrel within 15 hours of the procedure and 35 in those administered clopidogrel more that 15 hours before the index PCI
Subsequently the benefit of higher doses of clopidogrel was studied both ex vivo and in clinical studies PRONTO A 600 mg dose of clopidogrel achieved adequate platelet inhibition within 2 hours of administration unlike 300 mg that required at least 3 to 6 hours to achieve full effect Subsequent data from the ISAR-REACT investigators in 2159 patients showed that the benefit of 600 mg of clopidogrel was not time dependent The trial focused on the possible additional benefit of glycoprotein IIbIIIa inhibition in these patients who had all been pre-treated with 600 mg of clopidogrel More recently ISAR-REACT-2 showed that clopidogrel pretreatment in moderate to high risk PCI patients reduced the combined endpoint event rate relative to placebo from 117 to 57 in patients treated with glycoprotein IIbIIIa inhibitors and from 155 to 76 in those not receiving glycoprotein IIbIIIa inhibition The recently published Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation Inflammation and Ongoing Necrosis ALBION Trial showed in a low risk group of patients that 600 mg and 900 mg doses of clopidogrel provide faster and greater platelet inhibition than 300 mg as assessed by biochemical assays The study was underpowered to demonstrate clinical benefits but it showed a trend towards reduction in troponin-I release as a marker of necrosis from 58 to 42 in the higher dose clopidogrel groups There was no demonstrable increase in major bleeding complications 29 in both 300 and 900 mg groups but there was a statistically insignificant increase in minor bleeding in the 900 mg dose group
Our investigation will evaluate the safety and efficacy of pre-treatment 2 hours with 600 mg of clopidogrel in 600 outpatients undergoing elective cardiac catheterization with coronary angiography in our institution who have no evidence of high risk features such as ischemic ST segment deviations unstable angina recent myocardial infarction or abnormal troponin-T levels The benefit of clopidogrel in patients who undergo interventions may be offset by the bleeding complications encountered especially in patients who do not undergo coronary angioplasty Our trial is designed to assess this potential benefit-risk trade-off Unlike the ALBION trial we will focus on clinical outcomes using a larger sample size Our hypothesis is that pretreatment with 600 mg of clopidogrel will significantly reduce the incidence of ischemic complications in patients undergoing PCI but with possible increase in hemorrhagic and vascular complications in the overall population
In addition we will also examine whether the use of 5 French arterial sheaths in cases that do not go onto intervention offsets the increase in bleeding risk if any associated with pretreatment with 600 mg of clopidogrel Very large diameter arterial sheaths eg 10 French have been associated with higher vascular complication rates but whether 5 French sheaths offer lower vascular complication rates than 6 French sheaths is uncertain Nearly all PCIs at our institution are performed using 6 French sheaths which have larger lumens more accommodating of angioplasty equipment and higher injection rates of iodinated contrast Patients who undergo PCI following diagnostic angiography using a 5 French sheath will require exchange for a larger 6 French arterial sheath On the other hand patients who do not need angioplasty after coronary angiography will not require any exchange of their arterial sheath and those with smaller sheath sizes may well have less vascular and bleeding complications
DESCRIPTION OF RESEARCH PROTOCOL Design This is a prospective randomized clinical trial comparing ischemic hemorrhagic and vascular outcomes in outpatients undergoing elective cardiac catheterization with coronary angiography following 11 randomization to pretreatment with 600 mg clopidogrel vs no pretreatment and clopidogrel dosing post-procedure if a PCI is performed Patients will provide written informed consent prior to enrollment and randomization Since some operators may feel strongly about using glycoprotein IIbIIIa inhibition in patients who did not receive clopidogrel well in advance of the PCI blinding of the loading strategy and use of a placebo are not feasible A separate 11 randomization will assign patients to undergo cardiac catheterization using 5 or 6 French arterial introducing sheaths Since the arterial sheath sizes are color-coded catheter sizes are imprinted on each catheter and the operator must know the arterial sheath size in case alternate catheters are required blinding of sheath size assignment is also not feasible The investigator adjudicating and abstracting the outcomes data such as bleeding and ischemic complications for analysis will be blinded however to the clopidogrel reimen and randomization in order to avoid any bias
Hypotheses to be tested The primary hypothesis being examined is that clopidogrel 600 mg given 2 hours prior to cardiac catheterization will reduce the frequency of post-procedural ischemic events in the subset of patients who undergo ad hoc coronary interventions compared with those who do not receive clopidogrel pre-procedure The risk of hemorrhagic and vascular complications by preloading strategy will be evaluated in all patients randomized encompassing those who do and those who do not undergo PCI Additional analyses will be performed to see if the size of the initial arterial introducing sheath also has an effect on the rate of hemorrhagic and vascular complications and if there is any interaction of sheath size with preloading strategy on these outcomes
Patient population All outpatients undergoing elective cardiac catheterization with planned coronary angiography with possible ad hoc PCI if lesion anatomy suitable and who have not received clopidogrel or ticlopidine during the 14 days prior to the procedure are eligible Patients with high-risk clinical features contraindications to clopidogrel or planned upcoming invasive procedures will be excluded vide infra
Procedural factors The decision to perform ad hoc PCI after diagnostic coronary angiography vs medical therapy or bypass surgery will be made by the interventional cardiologist performing or overseeing the cardiac catheterization in consultation with the patients clinical cardiologists The specific angioplasty techniques devices equipment anti-thrombin and anti-platelet pharmacological regimen to be utilized are NOT specified by this protocol and are at the discretion of the interventional cardiologist
Patients randomized to 5 French arterial sheaths and NO clopidogrel preloading will be allowed to ambulate 2 hours after arterial hemostasis is achieved with delayed ambulation if bleeding or orthostatic hypotension occurs All other participants ie 6 French arterial sheaths or 5 French arterial sheaths with clopidogrel preloading will be allowed to ambulate no earlier than 4 hours after hemostasis occurs
Variables of interest include baseline demographic and clinical characteristics including age gender left ventricular ejection fraction diabetes mellitus hypertension dyslipidemia chronic renal insufficiency serum creatinine level tobacco use extent of coronary disease symptom severity prior myocardial infarction prior PCI prior CABG angiographic lesion characteristics eg bifurcation location lesion class procedural factors eg pharmacological antithrombin regimen glycoprotein IIbIIIa inhibitor use and post-procedural tests including serum creatinine serum creatine kinase and its MB isoform troponin-T and radiological imaging studies Information will be gleaned from the Cardiac Catheterization Laboratory Quality Assurance Database from electronic medical records from review of the procedural angiograms and conversations with the patient or if the patient cannot be located their family or health care providers
Endpoints All endpoints will be assessed at 14 days post-procedure and divided for analytical purposes into in-hospital and post-discharge events See Endpoint section of this document for details
Follow-up Written and electronic medical records will be reviewed to identify clinical events occurring during the hospitalization through the 1st 14 days post-procedure if the length of stay is prolonged Participants will have provided written informed consent for clinical follow-up at 14 days post-procedure prior to entry into this study and contact information for the patient hisher primary care provider hisher cardiologist and hisher next of kin will be collected before discharge The patient hisher physicians or hisher next of kin will be contacted by telephone at 14 or more days post-procedure and asked if the patient was treated after discharge for any heart-related bleeding or vascular access site problems ie any of the clinical events detailed above If yes attempts will be made with the patients authorization to obtain more information about the event including requests for documentation from other health care facilities and providers
Data Monitoring and Safety Plan A independent data safety monitoring committee DSMC comprised of Murray Mittleman MD DrPH BIDMC cardiovascular epidemiologist serving as Chair David J Cohen MD MSc interventional cardiologist at the Mid America Heart Institute and Shiva Gautam PhD BIDMC biostatistician will review the rates of the 4 composite endpoints enumerated above after 14 day follow-up has been completed on the 1st 300 subjects enrolled The DSMC will advise the principal investigator whether the study should terminated because of concerning and striking differences in the ischemic or vascularbleeding complication rates between treatment strategies or if the study should be allowed to continue to the planned enrollment of 600 participants Study recruitment will be suspended during the DSMCs review and deliberations
Data Management Much of the data required for this study is routinely collected as part of current clinical care quality assurance and regulatory processes and stored in the Cardiac Catheterization Laboratory Quality Assurance Database residing a commercial application named Apollo and manufactured by Lumedx The fields of interest for patients randomized in this study will be queried form the Apollo database and transferred directly to the Access database that serves as the primary electronic data repository for this study This database will be housed on a network server within the BIDMC firewall with restricted access password and valid user identification required Additional information from medical records or patient contacts will be collected on paper case report forms prior to entry into the Access database All case report forms and paper clinical information with patient identifiers will be stored in a locked file drawer within a locked office Angiograms will be reviewed using clinical workstations in physically secured areas and electronic copies of angiograms will be made with all patient identifiers electronically removed Medical record numbers and names will be removed prior to creation of final analytical dataset All paper and electronic information will be destroyed in a HIPAA-compliant fashion after completion and publication of this study
Statistical Considerations Randomization A randomization scheme will be prepared using 1111 ratios for the 2 clopidogrel dosing strategies combined independently with 5 vs 6 French arterial sheaths with permuted blocks of random sizes of 4 or 8 The treatment assignment will be designated in opaque tamper-resistant randomization envelopes provided by the Statistical Department of the Harvard Clinical Research Institute
Statistical Analysis All statistical analyses will be performed using SAS for Windows v9 The primary analysis will compare the cumulative incidence at 14 days of the primary composite endpoint any death myocardial infarction or myocardial necrosis in patients with PCI attempted between those randomized to clopidogrel loading vs those randomized to standard clopidogrel administration using the Fishers exact test A p value of 005 or less will be required for statistical significance The secondary endpoint of stent thrombosis among those who undergo stent deployment will also be evaluated using Fishers exact test The other endpoints including vascular and bleeding will be examined in all patients randomized and not just subsets who had PCI attempted or stents deployed Two group comparisons clopidogrel loading vs standard dosing 5 French vs 6 French arterial sheaths and 4 group comparisons the 4 combinations of clopidogrel dosing strategy and arterial sheath size or subgroups with PCI or no PCI by clopidogrel dosing strategy will be performed using Fishers exact test t-tests ANOVA or analogous non-parametric tests as appropriate Since multiple exploratory analyses will be performed p-values for everything other than the primary analysis delineated above must be interpreted with caution Logistical regression models will also be constructed to identify pre-procedural predictors of ischemic and of bleeding or vascular complications
Subsequently the benefit of higher doses of clopidogrel was studied both ex vivo and in clinical studies PRONTO A 600 mg dose of clopidogrel achieved adequate platelet inhibition within 2 hours of administration unlike 300 mg that required at least 3 to 6 hours to achieve full effect Subsequent data from the ISAR-REACT investigators in 2159 patients showed that the benefit of 600 mg of clopidogrel was not time dependent The trial focused on the possible additional benefit of glycoprotein IIbIIIa inhibition in these patients who had all been pre-treated with 600 mg of clopidogrel More recently ISAR-REACT-2 showed that clopidogrel pretreatment in moderate to high risk PCI patients reduced the combined endpoint event rate relative to placebo from 117 to 57 in patients treated with glycoprotein IIbIIIa inhibitors and from 155 to 76 in those not receiving glycoprotein IIbIIIa inhibition The recently published Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation Inflammation and Ongoing Necrosis ALBION Trial showed in a low risk group of patients that 600 mg and 900 mg doses of clopidogrel provide faster and greater platelet inhibition than 300 mg as assessed by biochemical assays The study was underpowered to demonstrate clinical benefits but it showed a trend towards reduction in troponin-I release as a marker of necrosis from 58 to 42 in the higher dose clopidogrel groups There was no demonstrable increase in major bleeding complications 29 in both 300 and 900 mg groups but there was a statistically insignificant increase in minor bleeding in the 900 mg dose group
Our investigation will evaluate the safety and efficacy of pre-treatment 2 hours with 600 mg of clopidogrel in 600 outpatients undergoing elective cardiac catheterization with coronary angiography in our institution who have no evidence of high risk features such as ischemic ST segment deviations unstable angina recent myocardial infarction or abnormal troponin-T levels The benefit of clopidogrel in patients who undergo interventions may be offset by the bleeding complications encountered especially in patients who do not undergo coronary angioplasty Our trial is designed to assess this potential benefit-risk trade-off Unlike the ALBION trial we will focus on clinical outcomes using a larger sample size Our hypothesis is that pretreatment with 600 mg of clopidogrel will significantly reduce the incidence of ischemic complications in patients undergoing PCI but with possible increase in hemorrhagic and vascular complications in the overall population
In addition we will also examine whether the use of 5 French arterial sheaths in cases that do not go onto intervention offsets the increase in bleeding risk if any associated with pretreatment with 600 mg of clopidogrel Very large diameter arterial sheaths eg 10 French have been associated with higher vascular complication rates but whether 5 French sheaths offer lower vascular complication rates than 6 French sheaths is uncertain Nearly all PCIs at our institution are performed using 6 French sheaths which have larger lumens more accommodating of angioplasty equipment and higher injection rates of iodinated contrast Patients who undergo PCI following diagnostic angiography using a 5 French sheath will require exchange for a larger 6 French arterial sheath On the other hand patients who do not need angioplasty after coronary angiography will not require any exchange of their arterial sheath and those with smaller sheath sizes may well have less vascular and bleeding complications
DESCRIPTION OF RESEARCH PROTOCOL Design This is a prospective randomized clinical trial comparing ischemic hemorrhagic and vascular outcomes in outpatients undergoing elective cardiac catheterization with coronary angiography following 11 randomization to pretreatment with 600 mg clopidogrel vs no pretreatment and clopidogrel dosing post-procedure if a PCI is performed Patients will provide written informed consent prior to enrollment and randomization Since some operators may feel strongly about using glycoprotein IIbIIIa inhibition in patients who did not receive clopidogrel well in advance of the PCI blinding of the loading strategy and use of a placebo are not feasible A separate 11 randomization will assign patients to undergo cardiac catheterization using 5 or 6 French arterial introducing sheaths Since the arterial sheath sizes are color-coded catheter sizes are imprinted on each catheter and the operator must know the arterial sheath size in case alternate catheters are required blinding of sheath size assignment is also not feasible The investigator adjudicating and abstracting the outcomes data such as bleeding and ischemic complications for analysis will be blinded however to the clopidogrel reimen and randomization in order to avoid any bias
Hypotheses to be tested The primary hypothesis being examined is that clopidogrel 600 mg given 2 hours prior to cardiac catheterization will reduce the frequency of post-procedural ischemic events in the subset of patients who undergo ad hoc coronary interventions compared with those who do not receive clopidogrel pre-procedure The risk of hemorrhagic and vascular complications by preloading strategy will be evaluated in all patients randomized encompassing those who do and those who do not undergo PCI Additional analyses will be performed to see if the size of the initial arterial introducing sheath also has an effect on the rate of hemorrhagic and vascular complications and if there is any interaction of sheath size with preloading strategy on these outcomes
Patient population All outpatients undergoing elective cardiac catheterization with planned coronary angiography with possible ad hoc PCI if lesion anatomy suitable and who have not received clopidogrel or ticlopidine during the 14 days prior to the procedure are eligible Patients with high-risk clinical features contraindications to clopidogrel or planned upcoming invasive procedures will be excluded vide infra
Procedural factors The decision to perform ad hoc PCI after diagnostic coronary angiography vs medical therapy or bypass surgery will be made by the interventional cardiologist performing or overseeing the cardiac catheterization in consultation with the patients clinical cardiologists The specific angioplasty techniques devices equipment anti-thrombin and anti-platelet pharmacological regimen to be utilized are NOT specified by this protocol and are at the discretion of the interventional cardiologist
Patients randomized to 5 French arterial sheaths and NO clopidogrel preloading will be allowed to ambulate 2 hours after arterial hemostasis is achieved with delayed ambulation if bleeding or orthostatic hypotension occurs All other participants ie 6 French arterial sheaths or 5 French arterial sheaths with clopidogrel preloading will be allowed to ambulate no earlier than 4 hours after hemostasis occurs
Variables of interest include baseline demographic and clinical characteristics including age gender left ventricular ejection fraction diabetes mellitus hypertension dyslipidemia chronic renal insufficiency serum creatinine level tobacco use extent of coronary disease symptom severity prior myocardial infarction prior PCI prior CABG angiographic lesion characteristics eg bifurcation location lesion class procedural factors eg pharmacological antithrombin regimen glycoprotein IIbIIIa inhibitor use and post-procedural tests including serum creatinine serum creatine kinase and its MB isoform troponin-T and radiological imaging studies Information will be gleaned from the Cardiac Catheterization Laboratory Quality Assurance Database from electronic medical records from review of the procedural angiograms and conversations with the patient or if the patient cannot be located their family or health care providers
Endpoints All endpoints will be assessed at 14 days post-procedure and divided for analytical purposes into in-hospital and post-discharge events See Endpoint section of this document for details
Follow-up Written and electronic medical records will be reviewed to identify clinical events occurring during the hospitalization through the 1st 14 days post-procedure if the length of stay is prolonged Participants will have provided written informed consent for clinical follow-up at 14 days post-procedure prior to entry into this study and contact information for the patient hisher primary care provider hisher cardiologist and hisher next of kin will be collected before discharge The patient hisher physicians or hisher next of kin will be contacted by telephone at 14 or more days post-procedure and asked if the patient was treated after discharge for any heart-related bleeding or vascular access site problems ie any of the clinical events detailed above If yes attempts will be made with the patients authorization to obtain more information about the event including requests for documentation from other health care facilities and providers
Data Monitoring and Safety Plan A independent data safety monitoring committee DSMC comprised of Murray Mittleman MD DrPH BIDMC cardiovascular epidemiologist serving as Chair David J Cohen MD MSc interventional cardiologist at the Mid America Heart Institute and Shiva Gautam PhD BIDMC biostatistician will review the rates of the 4 composite endpoints enumerated above after 14 day follow-up has been completed on the 1st 300 subjects enrolled The DSMC will advise the principal investigator whether the study should terminated because of concerning and striking differences in the ischemic or vascularbleeding complication rates between treatment strategies or if the study should be allowed to continue to the planned enrollment of 600 participants Study recruitment will be suspended during the DSMCs review and deliberations
Data Management Much of the data required for this study is routinely collected as part of current clinical care quality assurance and regulatory processes and stored in the Cardiac Catheterization Laboratory Quality Assurance Database residing a commercial application named Apollo and manufactured by Lumedx The fields of interest for patients randomized in this study will be queried form the Apollo database and transferred directly to the Access database that serves as the primary electronic data repository for this study This database will be housed on a network server within the BIDMC firewall with restricted access password and valid user identification required Additional information from medical records or patient contacts will be collected on paper case report forms prior to entry into the Access database All case report forms and paper clinical information with patient identifiers will be stored in a locked file drawer within a locked office Angiograms will be reviewed using clinical workstations in physically secured areas and electronic copies of angiograms will be made with all patient identifiers electronically removed Medical record numbers and names will be removed prior to creation of final analytical dataset All paper and electronic information will be destroyed in a HIPAA-compliant fashion after completion and publication of this study
Statistical Considerations Randomization A randomization scheme will be prepared using 1111 ratios for the 2 clopidogrel dosing strategies combined independently with 5 vs 6 French arterial sheaths with permuted blocks of random sizes of 4 or 8 The treatment assignment will be designated in opaque tamper-resistant randomization envelopes provided by the Statistical Department of the Harvard Clinical Research Institute
Statistical Analysis All statistical analyses will be performed using SAS for Windows v9 The primary analysis will compare the cumulative incidence at 14 days of the primary composite endpoint any death myocardial infarction or myocardial necrosis in patients with PCI attempted between those randomized to clopidogrel loading vs those randomized to standard clopidogrel administration using the Fishers exact test A p value of 005 or less will be required for statistical significance The secondary endpoint of stent thrombosis among those who undergo stent deployment will also be evaluated using Fishers exact test The other endpoints including vascular and bleeding will be examined in all patients randomized and not just subsets who had PCI attempted or stents deployed Two group comparisons clopidogrel loading vs standard dosing 5 French vs 6 French arterial sheaths and 4 group comparisons the 4 combinations of clopidogrel dosing strategy and arterial sheath size or subgroups with PCI or no PCI by clopidogrel dosing strategy will be performed using Fishers exact test t-tests ANOVA or analogous non-parametric tests as appropriate Since multiple exploratory analyses will be performed p-values for everything other than the primary analysis delineated above must be interpreted with caution Logistical regression models will also be constructed to identify pre-procedural predictors of ischemic and of bleeding or vascular complications
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None