SAVI-PCI: Shortened Aggrastat® Versus Integrilin in Percutaneous Coronary Intervention

• Sponsor: Medicure (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01522417
• Collaborator: SCRI Development Innovations, LLC (Other)
• Enrollment: 535
• Locations: 13
• Arms: 3
• Duration (Months): 83
• Patients Per Site: 41.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose this study is to assess whether a tirofiban regimen of a high-dose bolus plus a shortened infusion duration compared to label-dosing eptifibatide in patients undergoing percutaneous coronary intervention (PCI) is associated with a non-inferior composite rate of death, PCI-related myocardial infarction, urgent target vessel revascularization or in-hospital major bleeding within 48 hours following PCI or hospital discharge, whichever comes first.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction; Acute Coronary Syndromes; Unstable Angina	Drug: Short Tirofiban; Drug: Eptifibatide; Drug: Long Tirofiban	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 535 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Open-Label Study to Evaluate the Efficacy of Tirofiban Using a High-Dose Bolus Plus a Shortened Infusion Duration Versus Label-Dosing Eptifibatide in Patients Undergoing Percutaneous Coronary Intervention
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Short Tirofiban (Aggrastat) Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines).	Drug: Short Tirofiban; 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.; Other Names: Aggrastat
Active Comparator: Eptifibatide (Integrilin) Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines).	Drug: Eptifibatide; 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.; Other Names: Integrilin
Experimental: Long Tirofiban (Aggrastat) Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines).	Drug: Long Tirofiban; 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.; Other Names: Aggrastat

Outcome Measures

Primary Outcome Measures

1. The Composite Endpoint of Death, Periprocedural Myonecrosis (PPM), Urgent Target Vessel Revascularization (uTVR) or Major Bleeding [48 hours or hospital discharge, whichever came first]

   The composite of death (any-cause), periprocedural myonecrosis (defined as ≥ 3 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value), urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia) or non-CABG related major bleeding as quantified according to REPLACE-2 bleeding criteria.

Secondary Outcome Measures

1. The Composite Endpoint of Death, Periprocedural Myonecrosis or Urgent Target Vessel Revascularization [48 hours or hospital discharge, whichever came first]

   The composite of death (any-cause), periprocedural myonecrosis (defined as ≥ 3 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value), or urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia)

2. Individual Components of Death, Urgent Target Revascularization or Major Bleeding [48 hours or hospital discharge, whichever came first]

   Individual components of death (any-cause), urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia) or non-CABG related major bleeding as quantified according to REPLACE-2 major bleeding criteria.

3. Individual Components of Periprocedural Myonecrosis [48 hours or hospital discharge, whichever came first]

   Individual components of periprocedural myonecrosis (PPM) (defined as ≥ 3 times, ≥ 10 times, ≥ 20 times or ≥ 50 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value)

4. The Composite Endpoint of Death, Periprocedural Myonecrosis (PPM) (≥ 10x Troponin), Urgent Target Vessel Revascularization (uTVR) or Major Bleeding [48 hours or hospital discharge, whichever came first]

   The composite of death (any-cause), periprocedural myonecrosis (defined as ≥ 10 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value), urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia) or non-CABG related major bleeding as quantified according to REPLACE-2 bleeding criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18 years of age

• Scheduled to undergo PCI with an FDA, approved or cleared device (stent or procedures such as balloon angioplasty, rotoblation, AngioSculpt, laser atherectomy,etc.) in one or more native coronary target lesions

• Written informed consent

Exclusion Criteria:

• Primary PCI for STEMI as index procedure

• Prior STEMI within 48 hours before randomization

• Prior PCI within 30 days before randomization

• Planned staged PCI within the subsequent 24 hours after index PCI

• Use of abciximab within 7 days before randomization

• Use of tirofiban or eptifibatide within 12 hours before randomization

• Use of low-molecular weight heparin within 12 hours before randomization

• Use of bivalirudin within 12 hours before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Osceola Regional Medical Center	Kissimmee	Florida	United States	34741
2	Northside Hospital	Saint Petersburg	Florida	United States	33709
3	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
4	Emory University Hospital	Atlanta	Georgia	United States	30322
5	North Georgia Heart Center	Gainesville	Georgia	United States	30501
6	Redmond Regional Medical Center	Rome	Georgia	United States	30165
7	Archbold Medical Center	Thomasville	Georgia	United States	31792
8	Lenox Hill Hospital	New York	New York	United States	10075
9	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
10	Doylestown Hospital	Doylestown	Pennsylvania	United States	18901
11	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104
12	Centennial Heart	Nashville	Tennessee	United States	37203
13	Chippenham Hospital	Richmond	Virginia	United States	23225

Sponsors and Collaborators

• Medicure
• SCRI Development Innovations, LLC

Investigators

• Principal Investigator: Steven V Manoukian, MD, SCRI Development Innovations, LLC

Study Documents (Full-Text)

• Study Protocol - Feb 1, 2018
• Statistical Analysis Plan - Feb 20, 2019

More Information

Publications

None provided.

• Responsible Party: Medicure
• ClinicalTrials.gov Identifier: NCT01522417
• Other Study ID Numbers: Medicure 11002
• First Posted: Jan 31, 2012
• Last Update Posted: May 13, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Myocardial Infarction; Acute Coronary Syndrome; Angina, Unstable; Infarction; Tirofiban; Eptifibatide

Study Results

Participant Flow

Recruitment Details	Date first patient enrolled: 12 June 2012 ; Last patient completed 8 August 2018 The study enrolled both stable and UA/NSTEMI patients scheduled to undergo PCI in one or more native coronary target lesions.
Pre-assignment Detail	Decision to proceed to PCI, access site for PCI (transradial or transfemoral) and intended oral P2Y12 antagonist agent used post-randomization were all pre-specified prior to randomization to treatment groups.

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
Period Title: Overall Study
STARTED	209	202	124
COMPLETED	209	202	124
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)	Total
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.	Total of all reporting groups
Overall Participants	209	202	124	535
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (9.7)	63.7 (10.1)	62.6 (10.9)	63.3 (10.2)
Sex: Female, Male (Count of Participants)
Female	57 27.3%	61 30.2%	40 32.3%	158 29.5%
Male	152 72.7%	141 69.8%	84 67.7%	377 70.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 3.3%	7 3.5%	3 2.4%	17 3.2%
Not Hispanic or Latino	202 96.7%	195 96.5%	121 97.6%	518 96.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.8%	1 0.2%
Asian	4 1.9%	1 0.5%	1 0.8%	6 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.5%	0 0%	1 0.2%
Black or African American	27 12.9%	20 9.9%	18 14.5%	65 12.1%
White	175 83.7%	173 85.6%	103 83.1%	451 84.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	3 1.4%	7 3.5%	1 0.8%	11 2.1%
Region of Enrollment (participants) [Number]
United States	209 100%	202 100%	124 100%	535 100%

Outcome Measures

1. Primary Outcome

Title	The Composite Endpoint of Death, Periprocedural Myonecrosis (PPM), Urgent Target Vessel Revascularization (uTVR) or Major Bleeding
Description	The composite of death (any-cause), periprocedural myonecrosis (defined as ≥ 3 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value), urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia) or non-CABG related major bleeding as quantified according to REPLACE-2 bleeding criteria.
Time Frame	48 hours or hospital discharge, whichever came first

Outcome Measure Data

Analysis Population Description

As per the protocol, a patient must have a pre-PCI troponin measurement and at least one troponin measurement within 48 hours following PCI or hospital discharge, whichever comes first, otherwise they were excluded from the primary composite endpoint.

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
Measure Participants	202	194	123
Count of Participants [Participants]	69 33%	60 29.7%	48 38.7%

2. Secondary Outcome

Title	The Composite Endpoint of Death, Periprocedural Myonecrosis or Urgent Target Vessel Revascularization
Description	The composite of death (any-cause), periprocedural myonecrosis (defined as ≥ 3 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value), or urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia)
Time Frame	48 hours or hospital discharge, whichever came first

Outcome Measure Data

Analysis Population Description

As per the protocol, a patient must have a pre-PCI troponin measurement and at least one troponin measurement within 48 hours following PCI or hospital discharge, whichever comes first, otherwise they were excluded from the primary composite endpoint.

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
Measure Participants	202	194	123
Count of Participants [Participants]	69 33%	60 29.7%	45 36.3%

3. Secondary Outcome

Title	Individual Components of Death, Urgent Target Revascularization or Major Bleeding
Description	Individual components of death (any-cause), urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia) or non-CABG related major bleeding as quantified according to REPLACE-2 major bleeding criteria.
Time Frame	48 hours or hospital discharge, whichever came first

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
Measure Participants	209	202	124
Death	0 0%	1 0.5%	0 0%
uTVR	1 0.5%	0 0%	1 0.8%
REPLACE-2 Major Bleeding	0 0%	1 0.5%	4 3.2%

4. Secondary Outcome

Title	Individual Components of Periprocedural Myonecrosis
Description	Individual components of periprocedural myonecrosis (PPM) (defined as ≥ 3 times, ≥ 10 times, ≥ 20 times or ≥ 50 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value)
Time Frame	48 hours or hospital discharge, whichever came first

Outcome Measure Data

Analysis Population Description

As per the protocol, a patient must have a pre-PCI troponin measurement and at least one troponin measurement within 48 hours following PCI or hospital discharge, whichever comes first, otherwise they were excluded from the individual PPM endpoints.

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
Measure Participants	202	194	123
≥ 3 times ULN	69 33%	60 29.7%	45 36.3%
≥ 10 times ULN	36 17.2%	35 17.3%	28 22.6%
≥ 20 times ULN	19 9.1%	27 13.4%	21 16.9%
≥ 50 times ULN	11 5.3%	19 9.4%	9 7.3%

5. Secondary Outcome

Title	The Composite Endpoint of Death, Periprocedural Myonecrosis (PPM) (≥ 10x Troponin), Urgent Target Vessel Revascularization (uTVR) or Major Bleeding
Description	The composite of death (any-cause), periprocedural myonecrosis (defined as ≥ 10 times the upper limit of normal troponin and at least 20% or greater than the baseline troponin value), urgent target revascularization (repeat PCI or any CABG procedure after the index PCI on a non-selective basis in the target vessel because of recurrent myocardial ischemia) or non-CABG related major bleeding as quantified according to REPLACE-2 bleeding criteria.
Time Frame	48 hours or hospital discharge, whichever came first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Short Tirofiban (Aggrastat)	Eptifibatide (Integrilin)	Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.	Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
Measure Participants	202	194	123
Count of Participants [Participants]	36 17.2%	35 17.3%	32 25.8%

Adverse Events

Time Frame	48 hours or hospital discharge, whichever came first
Adverse Event Reporting Description	The Investigator periodically assessed patients for the occurrence of adverse events. To avoid bias in eliciting adverse events, patients were asked the following non-leading question: "How are you feeling?" All adverse events (serious and non-serious) reported by the patient will be followed until the event has resolved or has stabilized.
Arm/Group Title	Short Tirofiban (Aggrastat)		Eptifibatide (Integrilin)		Long Tirofiban (Aggrastat)
Arm/Group Description	Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Short Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion during a PCI plus 1 to 2 hours post-PCI.		Eptifibatide (Integrilin) will be dosed as a 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first. Patients will receive eptifibatide (Integrilin) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Eptifibatide: 180 mcg/kg bolus followed by a 2.0 mcg/kg/min infusion for 12 to 18 hours, with a second 180 mcg/kg bolus 10 min after the first.		Tirofiban (Aggrastat) will be dosed as a 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post PCI. Patients will receive tirofiban (Aggrastat) on a background of dual oral anti-platelet agents and unfractionated heparin (50 U/kg and repeat dosing per protocol guidelines). Long Tirofiban: 25 mcg/kg i.v. bolus followed by a 0.15 mcg/kg/min i.v. infusion for 12 to 18 hours post-PCI.
All Cause Mortality
	Short Tirofiban (Aggrastat)		Eptifibatide (Integrilin)		Long Tirofiban (Aggrastat)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/209 (0%)		1/202 (0.5%)		0/124 (0%)
Serious Adverse Events
	Short Tirofiban (Aggrastat)		Eptifibatide (Integrilin)		Long Tirofiban (Aggrastat)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/209 (3.8%)		11/202 (5.4%)		7/124 (5.6%)
Blood and lymphatic system disorders
Anaemia	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Cardiac disorders
Angina Pectoris	2/209 (1%)	2	1/202 (0.5%)	1	0/124 (0%)	0
Coronary Artery Dissection	2/209 (1%)	2	0/202 (0%)	0	0/124 (0%)	0
Cardiac Arrest	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Cardiac Tamponade	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Myocardial Infarction	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Eye disorders
Vision Blurred	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Gastrointestinal disorders
Gastrointestinal Angiodysplasia	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Gastrointestinal Haemorrhage	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Gastrointestinal Inflammation	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Immune system disorders
Contrast Media Allergy	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Injury, poisoning and procedural complications
Post-Procedural Myocardial Infarction	0/209 (0%)	0	3/202 (1.5%)	3	0/124 (0%)	0
Overdose	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Vascular pseudoaneurysm	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Nervous system disorders
Dizziness	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Product Issues
Thrombosis in Device	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Reproductive system and breast disorders
Testicular Haemorrhage	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Pulmonary Oedema	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Respiratory Failure	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Vascular disorders
Hypotension	0/209 (0%)	0	0/202 (0%)	0	2/124 (1.6%)	2
Haemorrhage	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Hypertensive Crisis	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Vessel Perforation	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Other (Not Including Serious) Adverse Events
	Short Tirofiban (Aggrastat)		Eptifibatide (Integrilin)		Long Tirofiban (Aggrastat)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/209 (21.5%)		55/202 (27.2%)		50/124 (40.3%)
Blood and lymphatic system disorders
Anaemia	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Cardiac disorders
Angina Pectoris	4/209 (1.9%)	4	2/202 (1%)	2	0/124 (0%)	0
Coronary Artery Dissection	2/209 (1%)	2	1/202 (0.5%)	1	0/124 (0%)	0
Bradycardia	0/209 (0%)	0	1/202 (0.5%)	1	1/124 (0.8%)	1
Myocardial Infarction	1/209 (0.5%)	1	1/202 (0.5%)	1	0/124 (0%)	0
Atrial Fibrillation	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Cardiac Arrest	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Cardiac Failure Congestive	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Cardiac Tamponade	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Intracardiac Thrombus	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Ventricular Tachycardia	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Eye disorders
Eye Pain	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Ocular Hyperaemia	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Vision Blurred	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Dizziness	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Gastrointestinal disorders
Nausea	0/209 (0%)	0	1/202 (0.5%)	1	1/124 (0.8%)	1
Abdominal Pain Upper	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Gastrointestinal Angiodysplasia	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Gastrointestinal Haemorrhage	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Gastrointestinal Inflammation	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Vomiting	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
General disorders
Catheter Site Haematoma	7/209 (3.3%)	7	8/202 (4%)	8	4/124 (3.2%)	4
Application Site Haemorrhage	1/209 (0.5%)	1	5/202 (2.5%)	5	2/124 (1.6%)	2
Infusion Site Haematoma	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Non-Cardiac Chest Pain	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Pain	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Pyrexia	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Vessel Puncture Site Haematoma	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Vessel Puncture Site Haemorrhage	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Immune system disorders
Contrast Media Allergy	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Injury, poisoning and procedural complications
Post Procedural Myocardial Infarction	0/209 (0%)	0	3/202 (1.5%)	3	2/124 (1.6%)	2
Incision Site Haematoma	3/209 (1.4%)	3	0/202 (0%)	0	1/124 (0.8%)	1
Incision Site Haemorrhage	0/209 (0%)	0	2/202 (1%)	2	0/124 (0%)	0
Vascular Pseudoaneurysm	1/209 (0.5%)	1	1/202 (0.5%)	1	0/124 (0%)	0
Wound Secretion	1/209 (0.5%)	1	1/202 (0.5%)	1	0/124 (0%)	0
Graft Haemorrhage	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Mental Status Change Postoperative	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Overdose	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Wound	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Investigations
Troponin Increased	8/209 (3.8%)	8	6/202 (3%)	6	4/124 (3.2%)	4
Haematocrit Decreased	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	2
Troponin T Increased	1/209 (0.5%)	1	0/202 (0%)	0	1/124 (0.8%)	1
Blood Creatinine Increased	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Blood Glucose Decreased	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Occult Blood Positive	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Troponin I Increased	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	0/209 (0%)	0	1/202 (0.5%)	1	1/124 (0.8%)	1
Groin Pain	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Neck Pain	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Patellofemoral Pain Syndrome	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Nervous system disorders
Neurological Decompensation	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Presyncope	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Product Issues
Thrombosis in Device	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Psychiatric disorders
Agitation	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Delirium	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Renal and urinary disorders
Haematuria	1/209 (0.5%)	1	0/202 (0%)	0	1/124 (0.8%)	1
Acute Kidney Injury	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Nephropathy	1/209 (0.5%)	1	0/202 (0%)	0	0/124 (0%)	0
Reproductive system and breast disorders
Testicular Haemorrhage	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/209 (0%)	0	1/202 (0.5%)	1	1/124 (0.8%)	1
Aspiration	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Bronchospasm	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0
Epitaxis	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Pulmonary Oedema	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Respiratory Failure	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Skin and subcutaneous tissue disorders
Petechiae	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Vascular disorders
Haematoma	2/209 (1%)	2	4/202 (2%)	4	1/124 (0.8%)	1
Hypotension	1/209 (0.5%)	1	0/202 (0%)	0	3/124 (2.4%)	3
Haemorrhage	1/209 (0.5%)	1	1/202 (0.5%)	1	0/124 (0%)	0
Vascular Dissection	1/209 (0.5%)	1	0/202 (0%)	0	1/124 (0.8%)	1
Embolism	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Hypertensive Crisis	0/209 (0%)	0	0/202 (0%)	0	1/124 (0.8%)	1
Vessel Perforation	0/209 (0%)	0	1/202 (0.5%)	1	0/124 (0%)	0

Limitations/Caveats

Randomization into the long tirofiban arm was initiated after 159 patients were already enrolled into either the short tirofiban or long eptifibatide arms.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.