Shortened Aggrastat® Versus Integrilin in Percutaneous Coronary Intervention

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01522417

Acronym

SAVI-PCI

Enrollment

535

Registered

2012-01-31

Start date

2012-04-30

Completion date

2019-03-31

Last updated

2021-05-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myocardial Infarction, Acute Coronary Syndromes, Unstable Angina

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.

Interventions

DRUGShort 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.

DRUGEptifibatide

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.

DRUGLong 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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)
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.
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)
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.

Countries

United States

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 details

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.

Participants by arm

Arm	Count
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). 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.	209
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). 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.	202
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). 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.	124
Total	535

Baseline characteristics

Characteristic	Short Tirofiban (Aggrastat)	Total	Long Tirofiban (Aggrastat)	Eptifibatide (Integrilin)
Age, Continuous	63.7 years STANDARD_DEVIATION 9.7	63.3 years STANDARD_DEVIATION 10.2	62.6 years STANDARD_DEVIATION 10.9	63.7 years STANDARD_DEVIATION 10.1
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants	17 Participants	3 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	202 Participants	518 Participants	121 Participants	195 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	4 Participants	6 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	27 Participants	65 Participants	18 Participants	20 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants	11 Participants	1 Participants	7 Participants
Race (NIH/OMB) White	175 Participants	451 Participants	103 Participants	173 Participants
Region of Enrollment United States	209 participants	535 participants	124 participants	202 participants
Sex: Female, Male Female	57 Participants	158 Participants	40 Participants	61 Participants
Sex: Female, Male Male	152 Participants	377 Participants	84 Participants	141 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 209	1 / 202	0 / 124
other Total, other adverse events	45 / 209	55 / 202	50 / 124
serious Total, serious adverse events	8 / 209	11 / 202	7 / 124

Outcome results

Primary

The Composite Endpoint of Death, Periprocedural Myonecrosis (PPM), Urgent Target Vessel Revascularization (uTVR) or Major Bleeding

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.