Simplified Anti-Thrombotic Therapy for FFR (SMART-FFR)

Evaluation of Simplified Anti-Thrombotic Therapy for Coronary Fractional Flow Reserve

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Procedure: FFR; Drug: Aspirin; Drug: Clopidogrel; Drug: Bivalirudin

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TIMI (Thrombolysis in Myocardial Infarction) Major and Minor Bleeding Scores	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	Hospital Stay and after 30 days post PCI
Sub-clinical Ischemic Events Measured by Troponin Levels Post-procedure		48 hours post procedure

Collaborators and Investigators

• Sponsor: Odessa Heart Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 22, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 10, 2015

Study Record Updates

• Last Update Posted (Estimate): February 3, 2017
• Last Update Submitted That Met QC Criteria: December 10, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Clopidogrel; Bivalirudin
• Other Study ID Numbers: 20095