RESIST: Aspirin Resistance and Percutaneous Coronary Intervention (PCI)

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT01103440
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate if aggressive antiplatelet therapy would reduce ischemic events in aspirin (ASA) resistant patients after percutaneous coronary intervention (PCI).

Condition or Disease	Intervention/Treatment	Phase
Stable Angina	Drug: Intravenous Glycoprotein inhibitor + ASA, Clopidogrel; Drug: Antiplatelet Therapy (ASA, Clopidogrel)	Phase 2

Detailed Description

This is the first US based randomized double blinded prospective study using triple antiplatelet therapy and double dose plavix maintenance dose in aspirin resistant patients undergoing elective PCI through femoral access. The primary outcome of this study is an elevation of cardiac enzymes within 24 hours after the PCI with a secondary outcome of a composite of major adverse cardiac events of death, MI, stent thrombosis and urgent revascularization and bleeding up to 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Pilot, Single-center Study, Investigator-Initiated Study to Look at an Aggressive Therapeutic Approach in Aspirin Resistant Patients Comparing to Standard for Patient Undergoing Percutaneous Coronary Intervention
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Conventional Strategy Patient receive 325 mg ASA orally and loading does of 600mg Clopidogrel at time of procedure	Drug: Antiplatelet Therapy (ASA, Clopidogrel); Standard antiplatelet PCI treatment; Other Names: Thienopyridines Ticlopidine Clopidogrel Prasugrel
Active Comparator: Aggressive Strategy Patient receive 325mg ASA orally and loading does of 600mg Clopidogrel at time of procedure with addition of IV GP IIb/IIIa inhibitor bolus intra procedurally	Drug: Intravenous Glycoprotein inhibitor + ASA, Clopidogrel; IV Glycoprotein IIb/IIIa inhibitor bolus intra procedurally; Other Names: Cangrelor Abciximab Eptifibatide Tirofiban

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Elevation of Cardiac Enzyme [24 hours]

   Number of participants with peri-procedural biomarker elevation defined as any elevation above baseline of CK-MB or Tn-I within 24 hours after completion of the procedure.

Secondary Outcome Measures

1. Number of Participants With Major Adverse Cardiac Event (MACE) [30 days]

   Number of participants with MACE which is any event of Death, MI, Stent Thrombosis, Urgent Revascularization, Bleeding. Major adverse cardiac events (MACE), defined as the composite of death, MI (CK-MB > 3 times normal), urgent revascularization and definite or probable stent thrombosis (ST) within 30 days. Stent thrombosis was defined according to the new academic research consortium definitions; 2) bleeding complications within 30 days. Major bleeding was defined as intracranial or intraocular bleeding or a drop in hemoglobin > 5 g/dL. Minor bleeding was defined as hemorrhage at the access site requiring intervention, hematoma with a diameter of at least 5 cm, a reduction in hemoglobin levels of at least 4 g/dL without an overt bleeding source or at least 3 g/dL with such a source, reoperation for bleeding or transfusion of a blood product.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age older than 18 years

• Scheduled for elective or ad-hos PCI

• Aspirin use daily for greater or equal to one week

• Aspirin resistant (ARU greater than or equal to 550 on Verify Now-ASA

Exclusion Criteria:

• Pre-procedural elevation of cardiac biomarkers (CK-MB greater or equal to 10.4ng/dl or Tnl greater or equal to 0.4ng/dl

• administration of any GP IIb/IIIa inhibitor, anticoagulation or lytic therapy in the previous 30 days

• Ongoing bleeding or bleeding diathesis, contraindications for anticoagulation or increased bleeding risk or history of bleeding in the last eight weeks

• Previous stroke or transient ischemic attack or any intracranial pathology in the last six months, major surgery or trauma within the previous six weeks

• Platelet count less than hundred thousand per cubic millimeter or hematocrit <33% or hemoglobin <11 g per deciliter

• Subjects who received full dose low molecular weight heparin within six hours prior to randomization

• Allergy or intolerance to any of the study drugs or the presence of any serious comorbidity with life expectancy of ≤1year

• Scheduled for saphenous vein graft intervention, chronic total occlusions or with impaired renal function (eGFR<60ml/min) or patients who were taking anticoagulants or antiplatelet agents other than aspirin and clopidogrel or nonsteroidal anti-inflammatory drugs within two weeks before the PCI procedure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Medical Center	New York	New York	United States	10029

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Annapoorna S Kini, MD MRCP, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Annapoorna Kini, Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01103440
• Other Study ID Numbers: GCO-07-0200
• First Posted: Apr 14, 2010
• Last Update Posted: Feb 14, 2018
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Annapoorna Kini, Professor, Icahn School of Medicine at Mount Sinai: Major Adverse Cardiovascular Event; MACE; Death; MI; CK MB greater 3x Normal; Urgent Revascularization; Stent Thrombosis; Bleeding
• Additional relevant MeSH terms: Angina, Stable; polysaccharide-K; Tirofiban; Ticlopidine; Abciximab; Clopidogrel; Prasugrel Hydrochloride; Cangrelor; Eptifibatide

Study Results

Participant Flow

Recruitment Details	330 patients were screened with 36 enrolled between April 2007 and December 2008

Arm/Group Title	Conventional Strategy	Aggressive Strategy
Arm/Group Description	Patient receive 325 mg ASA orally and loading does of 600mg Clopidogrel at time of procedure	Patient receive 325mg ASA orally and loading does of 600mg Clopidogrel at time of procedure with addition of IV GP IIb/IIIa inhibitor bolus intra procedurally
Period Title: Overall Study
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Conventional Strategy	Aggressive Strategy	Total
Arm/Group Description	Patient receive 325 mg ASA orally and loading does of 600mg Clopidogrel at time of procedure	Patient receive 325mg ASA orally and loading does of 600mg Clopidogrel at time of procedure with addition of IV GP IIb/IIIa inhibitor bolus intra procedurally	Total of all reporting groups
Overall Participants	18	18	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (10)	66.2 (9)	65.7 (9)
Sex: Female, Male (Count of Participants)
Female	6 33.3%	6 33.3%	12 33.3%
Male	12 66.7%	12 66.7%	24 66.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Elevation of Cardiac Enzyme
Description	Number of participants with peri-procedural biomarker elevation defined as any elevation above baseline of CK-MB or Tn-I within 24 hours after completion of the procedure.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conventional Strategy	Aggressive Strategy
Arm/Group Description	Patient receive 325 mg ASA orally and loading does of 600mg Clopidogrel at time of procedure	Patient receive 325mg ASA orally and loading does of 600mg Clopidogrel at time of procedure with addition of IV GP IIb/IIIa inhibitor bolus intra procedurally
Measure Participants	18	18
Count of Participants [Participants]	4 22.2%	2 11.1%

2. Secondary Outcome

Title	Number of Participants With Major Adverse Cardiac Event (MACE)
Description	Number of participants with MACE which is any event of Death, MI, Stent Thrombosis, Urgent Revascularization, Bleeding. Major adverse cardiac events (MACE), defined as the composite of death, MI (CK-MB > 3 times normal), urgent revascularization and definite or probable stent thrombosis (ST) within 30 days. Stent thrombosis was defined according to the new academic research consortium definitions; 2) bleeding complications within 30 days. Major bleeding was defined as intracranial or intraocular bleeding or a drop in hemoglobin > 5 g/dL. Minor bleeding was defined as hemorrhage at the access site requiring intervention, hematoma with a diameter of at least 5 cm, a reduction in hemoglobin levels of at least 4 g/dL without an overt bleeding source or at least 3 g/dL with such a source, reoperation for bleeding or transfusion of a blood product.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conventional Strategy	Aggressive Strategy
Arm/Group Description	Patient receive 325 mg ASA orally and loading does of 600mg Clopidogrel at time of procedure	Patient receive 325mg ASA orally and loading does of 600mg Clopidogrel at time of procedure with addition of IV GP IIb/IIIa inhibitor bolus intra procedurally
Measure Participants	18	18
Count of Participants [Participants]	5 27.8%	1 5.6%

Adverse Events

Arm/Group Title	Conventional Strategy		Aggressive Strategy
Arm/Group Description	Patient receive 325 mg ASA orally and loading does of 600mg Clopidogrel at time of procedure		Patient receive 325mg ASA orally and loading does of 600mg Clopidogrel at time of procedure with addition of IV GP IIb/IIIa inhibitor bolus intra procedurally
All Cause Mortality
	Conventional Strategy		Aggressive Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Serious Adverse Events
	Conventional Strategy		Aggressive Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Conventional Strategy		Aggressive Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/18 (83.3%)		4/18 (22.2%)
Blood and lymphatic system disorders
Major Bleeding	1/18 (5.6%)		0/18 (0%)
Minor Bleeding	2/18 (11.1%)		1/18 (5.6%)
Cardiac disorders
Stent thrombosis	2/18 (11.1%)		0/18 (0%)
Urgent Vascularization	2/18 (11.1%)		0/18 (0%)
Myocardial Infarction	2/18 (11.1%)		0/18 (0%)
Cardiac Enzyme Elevation: Troponin-I	4/18 (22.2%)		2/18 (11.1%)
Cardiac Enzyme Elevation: CK-MB	2/18 (11.1%)		1/18 (5.6%)

Limitations/Caveats

Small pilot study with a limited sample size and not powered to detect differences in individual ischemic endpoints. Study does not delineate an optimal dose of aspirin. Antiplatelet effect of aspirin may fluctuate in patients at the same dosage.

More Information

Certain Agreements

All Principal Investigators ARE 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.