SMART-FFR: Simplified Anti-Thrombotic Therapy for FFR

• Sponsor: Odessa Heart Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02384070
• Collaborator: (none)
• Enrollment: 300
• Arms: 3
• Duration (Months): 71

Study Details

Study Description

Brief Summary

Despite the routine use of procedural anti-coagulation and anti-platelet therapy for FFR calculation, no study has evaluated the optimal anti-thrombotic regimen in patients undergoing FFR. Therefore, the aim of the Evaluation of Simplified Anti-Thrombotic Therapy for Coronary Fractional Flow Reserve (SMART-FFR) study was to evaluate the safety of using a simplified anti-thrombotic regimen with only upstream dual anti-platelet therapy (DAT) with aspirin and clopidogrel, compared with anticoagulation plus single- or- DAT therapy in patients with intermediate coronary artery stenosis undergoing FFR calculation during elective coronary angiography.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Procedure: FFR; Drug: Aspirin; Drug: Clopidogrel; Drug: Bivalirudin	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of Simplified Anti-Thrombotic Therapy for Coronary Fractional Flow Reserve
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Received upstream aspirin plus clopidogrel with no intra-procedural anticoagulation for the FFR calculation with a saline bolus and drip used for placebo anticoagulation during the procedure to blind the operator	Procedure: FFR; Fractional flow reserve tracings were calculated using a Volcano pressure wire intra-coronary system after ensuring proper calibration of the aortic pressure transducer and the guidewire, using 6 Fr-guide catheters. Before crossing the stenosis, baseline pressure was measured by the guide catheter and the pressure guidewire were equalized according to the manufacturer's specifications. After advancing the pressure sensor across the stenosis, coronary hyperemia was induced using intravenous adenosine (140μg/kg/min until a steady state was reached for at least 3 minutes). Fractional flow reserve was considered positive if it was less than 0.80.; Other Names: Fractional Flow Reserve ; Drug: Aspirin; All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure; Drug: Clopidogrel; All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure
Active Comparator: Group 2 Received upstream aspirin and clopidogrel plus intra-procedural anticoagulation with bivalirudin for FFR calculation	Procedure: FFR; Fractional flow reserve tracings were calculated using a Volcano pressure wire intra-coronary system after ensuring proper calibration of the aortic pressure transducer and the guidewire, using 6 Fr-guide catheters. Before crossing the stenosis, baseline pressure was measured by the guide catheter and the pressure guidewire were equalized according to the manufacturer's specifications. After advancing the pressure sensor across the stenosis, coronary hyperemia was induced using intravenous adenosine (140μg/kg/min until a steady state was reached for at least 3 minutes). Fractional flow reserve was considered positive if it was less than 0.80.; Other Names: Fractional Flow Reserve ; Drug: Aspirin; All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure; Drug: Clopidogrel; All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure; Drug: Bivalirudin; Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure
Experimental: Group 3 Received only upstream single anti-platelet therapy with aspirin plus intra-procedural anticoagulation for the FFR calculation with bivalirudin	Procedure: FFR; Fractional flow reserve tracings were calculated using a Volcano pressure wire intra-coronary system after ensuring proper calibration of the aortic pressure transducer and the guidewire, using 6 Fr-guide catheters. Before crossing the stenosis, baseline pressure was measured by the guide catheter and the pressure guidewire were equalized according to the manufacturer's specifications. After advancing the pressure sensor across the stenosis, coronary hyperemia was induced using intravenous adenosine (140μg/kg/min until a steady state was reached for at least 3 minutes). Fractional flow reserve was considered positive if it was less than 0.80.; Other Names: Fractional Flow Reserve ; Drug: Aspirin; All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure; Drug: Bivalirudin; Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure

Outcome Measures

Primary Outcome Measures

1. Thrombotic Complications [Hospital Stay and after 30 days post PCI]

Secondary Outcome Measures

1. TIMI (Thrombolysis in Myocardial Infarction) Major and Minor Bleeding Scores [Hospital Stay and after 30 days post PCI]

   Major: Intracranial bleeding, Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in haematocrit or Fatal bleeding. Minor: Clinically overt (including imaging), resulting in hemoglobin drop of 3 to <5 g/dL or ≥10% decrease in haematocrit. No observed blood loss: ≥4 g/dL decrease in the haemoglobin concentration or ≥12% decrease in haematocrit Any overt sign of hemorrhage that meets one of the following criteria and does not meet criteria for a major or minor bleeding event, as defined above Requiring intervention

2. Sub-clinical Ischemic Events Measured by Troponin Levels Post-procedure [48 hours post procedure]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patient regardless of sex, or age were eligible for the study if they were scheduled for an elective coronary angiography using a femoral approach, and were agreeable to participate in the study after signing informed consent, and had a coronary stenosis in any major native epicardial coronary artery between 50-70% determined by quantitative angiography that was an adequate target for FFR at the discretion of the operator.

Exclusion Criteria:

• Exclusion criteria included patients requiring mandatory DAT, patient undergoing radial access due to concomitant anticoagulation, patients with contra-indications or intolerant to DAT, patients with severe left ventricular hypertrophy defined as a wall thickness greater than 14 mm by echocardiography in the septal or lateral wall, patients with hypertrophic cardiomyopathy, left ventricular function less than 30%, severe aortic valvular stenosis defined as an aortic valve area of less than 1 cm2, presenting with an acute coronary syndrome in the past two weeks, hemodynamic instability, cardiogenic shock, reported allergy to clopidogrel, aspirin or bivalirudin, planned to be anticoagulated during or previous to the time of the coronary angiography, using Prasugrel or Ticagrelor, patients with coronary arteries unsuitable for FFR calculation due to severe tortuousity and/or calcification, lesions supplied by a bypass conduit, any mental condition rendering the subject incapable to understand the nature, scope, and possible consequences of the study such that the patient is unable to give appropriate informed consent or refusal or inability to sign an informed consent .

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Odessa Heart Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fernando Boccalandro MD, MD FACC FSACI, Odessa Heart Institute
• ClinicalTrials.gov Identifier: NCT02384070
• Other Study ID Numbers: 20095
• First Posted: Mar 10, 2015
• Last Update Posted: Feb 3, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Coronary Artery Disease; Aspirin; Bivalirudin; Clopidogrel

Study Results

Participant Flow

Arm/Group Title	Group 1: Upstream Aspirin + Clopidrogel	Group 2: Upstream Aspirin and Clopidrogel Plus Bivalirudin	Group 3: Upstream Aspirin Plus Bivalirudin
Arm/Group Description	Received upstream aspirin plus clopidogrel with no intra-procedural anticoagulation for the FFR calculation with a saline bolus and drip used for placebo anticoagulation during the procedure to blind the operator	Received upstream aspirin and clopidogrel plus intra-procedural anticoagulation with bivalirudin for FFR calculation	Received only upstream single anti-platelet therapy with aspirin plus intra-procedural anticoagulation for the FFR calculation with bivalirudin
Period Title: Overall Study
STARTED	100	100	100
COMPLETED	100	100	100
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Group 1: Upstream Aspirin + Clopidrogel	Group 2: Upstream Aspirin and Clopidrogel Plus Bivalirudin	Group 3: Upstream Aspirin Plus Bivalirudin	Total
Arm/Group Description	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure	Total of all reporting groups
Overall Participants	100	100	100	300
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62 (9)	65 (10)	63 (8)	64 (3)
Gender (Count of Participants)
Female	38 38%	39 39%	35 35%	112 37.3%
Male	62 62%	61 61%	65 65%	188 62.7%
Region of Enrollment (participants) [Number]
United States	100 100%	100 100%	100 100%	300 100%

Outcome Measures

1. Primary Outcome

Title	Thrombotic Complications
Time Frame	Hospital Stay and after 30 days post PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure
Measure Participants	100	100	100
Number [Number of Patients]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments	Analysis of the variance was used and Chi-square test for categorical variables. A sample size was calculated for a 95% confidence level and a power of 80%, assuming a 10% difference between groups.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments	The prior threshold for statistical significance was P < 0.05
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	TIMI (Thrombolysis in Myocardial Infarction) Major and Minor Bleeding Scores
Description	Major: Intracranial bleeding, Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in haematocrit or Fatal bleeding. Minor: Clinically overt (including imaging), resulting in hemoglobin drop of 3 to <5 g/dL or ≥10% decrease in haematocrit. No observed blood loss: ≥4 g/dL decrease in the haemoglobin concentration or ≥12% decrease in haematocrit Any overt sign of hemorrhage that meets one of the following criteria and does not meet criteria for a major or minor bleeding event, as defined above Requiring intervention
Time Frame	Hospital Stay and after 30 days post PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure
Measure Participants	100	100	100
Number [Patients]	1	3	1

3. Secondary Outcome

Title	Sub-clinical Ischemic Events Measured by Troponin Levels Post-procedure
Time Frame	48 hours post procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure
Measure Participants	100	100	100
Number [participants]	0 0%	0 0%	0 0%

Adverse Events

Arm/Group Title	Group 1		Group 2		Group 3
Arm/Group Description	Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure		Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Clopidogrel: All patient receiving clopidogrel, were loaded with 600 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure		Aspirin: All patients received a chewable aspirin of 325 mg at least 6 hours before the procedure Bivalirudin: Dosed based on the weight at 0.75 mg/kg I.V. bolus dose followed by a 1.75 mg/kg/hr I.V. infusion for the duration of the procedure
All Cause Mortality
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/100 (0%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/100 (0%)		0/100 (0%)

Limitations/Caveats

[Not Specified]

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.