Tailored Use of Tirofiban for Non-ST-elevation Acute Coronary Syndrome Patients

• Sponsor: Seoul National University Bundang Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03114995
• Collaborator: (none)
• Enrollment: 140
• Arms: 3
• Actual Duration (Months): 44

Study Details

Study Description

Brief Summary

Investigators aimed to test the beneficial effect of tirofiban, a GPIIb/IIIa antagonist, for Non-ST-Elevation Acute Coronary Syndrome Patients who has high resistance to clopidogrel.

Condition or Disease	Intervention/Treatment	Phase
Non-ST Elevation Myocardial Infarction	Drug: Tirofiban	Phase 4

Detailed Description

Some patients have a poor response to dual antiplatelet therapy (DAPT), and it can result in a poor prognosis after percutaneous coronary intervention (PCI). Devices like Ultegra Rapid Platelet Function Analyzer (VerifyNow®) enable us to quantify platelet reactivity quickly in the catheter laboratory. This means that the poor responders to DAPT can be identified, and the patients' outcomes can be improved by providing additional antiplatelet agents. Tirofiban, a GP IIb/IIIa inhibitor, is a potent antiplatelet agent which is recommended for Non-ST-Elevation acute coronary syndrome (NSTE-ACS) with high risk at presentation. However, its role is not clear for patients stabilized with standard medical treatment but with a poor responsiveness to DAPT.

In this study, Investigators administered tirofiban on top of DAPT to patients with NSTE-ACS undergoing PCI who have a high platelet reactivity (HPR) identified by VerifyNow.

To the best of our knowledge, there are few studies conducted with tirofiban for tailored antiplatelet therapy. Moreover, this is the first randomized study with NSTE-ACS patients for tailored use of tirofiban under the guidance of platelet reactivity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Effect of Tailored Use of Tirofiban in Patients With Non-ST-elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
• Actual Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (high platelet reactivity - tirofiban) Patients with high platelet reactivity unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h	Drug: Tirofiban; Other Names: Agrastat
No Intervention: Control C1 (high platelet reactivity - no tirofiban) Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered
No Intervention: Control C2 (low platelet reactivity - no tirofiban) Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered

Outcome Measures

Primary Outcome Measures

1. Area Under Curve of Serial Cardiac Biomarkers [0,6,12,18,24,30,36 hours]

   An area under the curve of serial levels of Troponin I and creatine kinase-MB isoenzyme during 36 hours

Secondary Outcome Measures

1. Percentage of Participants With Periprocedural Myonecrosis [0,6,12,18,24,30,36 hours]

   Percentage of participants with periprocedural myonecrosis under the criteria described below. When the cardiac biomarkers before the procedure were within the 99th percentile upper reference limit (URL), more than a 5-fold elevation in the URL within 12 hours after percutaneous coronary intervention (PCI) was defined as periprocedural myonecrosis. If the cardiac biomarker level was already above the 99th percentile URL before the procedure and the trend was stationary or decreasing, a ≥20% increase compared to the previous level was considered periprocedural myonecrosis. If the trend was still increasing, the levels at the post-6 hour and 12-hour were compared to determine periprocedural myonecrosis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• diagnosed with NSTE-ACS who need PCI

• loaded with aspirin and clopidogrel at least 6 h before the procedure

Exclusion Criteria:

• thrombocytopenia (platelet count <100,000/μL)

• history of hemorrhagic stroke

• history of ischemic stroke in the recent 2 year

• history of major surgery 6 months prior

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Seoul National University Bundang Hospital

Investigators

• Principal Investigator: Tae-Jin Youn, PhD, Seoul National University Bundang Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tae-Jin Youn, Professor, Cardiovascular Center, Seoul National University Bundang Hospital
• ClinicalTrials.gov Identifier: NCT03114995
• Other Study ID Numbers: B-1111-140-001
• First Posted: Apr 14, 2017
• Last Update Posted: Jul 17, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Tae-Jin Youn, Professor, Cardiovascular Center, Seoul National University Bundang Hospital: Tirofiban; Resistance to antiplatelet agents
• Additional relevant MeSH terms: Myocardial Infarction; Acute Coronary Syndrome; Non-ST Elevated Myocardial Infarction; Infarction; Tirofiban

Study Results

Participant Flow

Recruitment Details	Consecutively enrolled patients who are already stabilized with standard medical treatment and diagnosed with Non-ST elevation acute coronary syndrome (NSTE-ACS) at Seoul National University Bundang Hospital from February 2012 to October 2015

Arm/Group Title	Group A (High Platelet Reactivity - Tirofiban)	Control C1 (High Platelet Reactivity - no Tirofiban)	Control C2(Low Platelet Reactivity - no Tirofiban)
Arm/Group Description	Patients with high platelet reactivity (HPR) unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h Tirofiban	Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered	Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered
Period Title: Overall Study
STARTED	31	31	78
COMPLETED	30	30	78
NOT COMPLETED	1	1	0

Baseline Characteristics

Arm/Group Title	Group A (High Platelet Reactivity - Tirofiban)	Control C1 (High Platelet Reactivity - no Tirofiban)	Control C2 (Low Platelet Reactivity - no Tirofiban)	Total
Arm/Group Description	Patients with high platelet reactivity unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h Tirofiban	Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered	Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered	Total of all reporting groups
Overall Participants	30	30	78	138
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.0 (12.8)	64.5 (12.0)	62.9 (10.1)	64.8 (11.4)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	5 16.7%	11 14.1%	29 21%
Male	17 56.7%	25 83.3%	67 85.9%	109 79%

Outcome Measures

1. Primary Outcome

Title	Area Under Curve of Serial Cardiac Biomarkers
Description	An area under the curve of serial levels of Troponin I and creatine kinase-MB isoenzyme during 36 hours
Time Frame	0,6,12,18,24,30,36 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (High Platelet Reactivity - Tirofiban)	Control C1 (High Platelet Reactivity - no Tirofiban)	Control C2 (Low Platelet Reactivity - no Tirofiban)
Arm/Group Description	Patients with high platelet reactivity unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h Tirofiban	Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered	Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered
Measure Participants	30	30	78
Troponin I	197.2	38.0	121.4
creatine kinase-MB isoenzyme	252.5	92.7	185.6

2. Secondary Outcome

Title	Percentage of Participants With Periprocedural Myonecrosis
Description	Percentage of participants with periprocedural myonecrosis under the criteria described below. When the cardiac biomarkers before the procedure were within the 99th percentile upper reference limit (URL), more than a 5-fold elevation in the URL within 12 hours after percutaneous coronary intervention (PCI) was defined as periprocedural myonecrosis. If the cardiac biomarker level was already above the 99th percentile URL before the procedure and the trend was stationary or decreasing, a ≥20% increase compared to the previous level was considered periprocedural myonecrosis. If the trend was still increasing, the levels at the post-6 hour and 12-hour were compared to determine periprocedural myonecrosis.
Time Frame	0,6,12,18,24,30,36 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (High Platelet Reactivity - Tirofiban)	Control C1 (High Platelet Reactivity - no Tirofiban)	Control C2 (Low Platelet Reactivity - no Tirofiban)
Arm/Group Description	Patients with high platelet reactivity unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h Tirofiban	Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered	Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered
Measure Participants	30	30	78
Troponin I	16 53.3%	15 50%	26 33.3%
creatine kinase-MB isoenzyme	11 36.7%	10 33.3%	25 32.1%

Adverse Events

Time Frame	1 month
Arm/Group Title	Group A (High Platelet Reactivity - Tirofiban)		Control C1 (High Platelet Reactivity - no Tirofiban)		Control C2 (Low Platelet Reactivity - no Tirofiban)
Arm/Group Description	Patients with high platelet reactivity unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h Tirofiban		Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered		Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered
All Cause Mortality
	Group A (High Platelet Reactivity - Tirofiban)		Control C1 (High Platelet Reactivity - no Tirofiban)		Control C2 (Low Platelet Reactivity - no Tirofiban)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		0/30 (0%)		0/78 (0%)
Serious Adverse Events
	Group A (High Platelet Reactivity - Tirofiban)		Control C1 (High Platelet Reactivity - no Tirofiban)		Control C2 (Low Platelet Reactivity - no Tirofiban)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	Group A (High Platelet Reactivity - Tirofiban)		Control C1 (High Platelet Reactivity - no Tirofiban)		Control C2 (Low Platelet Reactivity - no Tirofiban)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/30 (13.3%)		1/30 (3.3%)		8/78 (10.3%)
Blood and lymphatic system disorders
Minor bleeding	4/30 (13.3%)	4	1/30 (3.3%)	1	8/78 (10.3%)	8

Limitations/Caveats

The difference in the distribution of PRU values of subjects estimated from previous literatures leading to small numbers of subjects assigned to the study group

More Information

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.