Conditions: Coronary Artery Disease
Keywords: ticagrelor cangrelor switching
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 22
Healthy volunteers: no

Brief summary:
Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a drug-drug interaction when ticagrelor is administered prior to cangrelor infusion.

Detailed description:
Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. In particular, ruling out a drug-drug interaction (DDI) is critical to this extent as the presence of a DDI would translate into reduced or abolished antiplatelet effects exposing these acute patients to an increased thrombotic risk. Despite the available evidence suggesting a lack of DDI with the use of ticagrelor in cangrelor treated patients, most data derive from studies in which ticagrelor was given at the time of initiation or during cangrelor infusion. To date, there is no data to fully rule out a DDI when ticagrelor is given prior to starting cangrelor infusion. The need for such investigation is underscored by the relatively high prevalence of pretreatment with ticagrelor in acute settings. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a DDI when ticagrelor is administered prior to cangrelor infusion.

Arms:
arm 1: Ticagrelor loading dose followed after 1 hour by cangrelor bolus and infusion arm 2: Ticagrelor loading dose followed after 1 hour by placebo infusion

Interventions: intervention 1: Cangrelor intervention 2: Placebo
Intervention descriptions: intervention 1: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase intervention 2: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase

Protocol document:
Prot_SAP_000.pdf: 
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Pharmacodynamic and pharmacokinetic profiles of switching between cangrelor and 
ticagrelor following ticagrelor pre-treatment:  
The Switching Antiplatelet -5 (SWAP-5) study 
 
 
 
 
 
 
 
 
Francesco Franchi, MD 
Assistant Professor of Medicine 
Division of Cardiology 
University of Florida College of Medicine - Jacksonville 
655 West 8th Street 
Jacksonville, FL – 32209 
Tel: +1-904-244-2060, Fax: 904-244-3102 
francesco.franchi@jax.ufl.edu 
 
 
 


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PROJECT SUMMARY 
Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet 
inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing 
coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly 
utilized, there is very limited data on the optimal approach for switching between these therapies. 
In particular, ruling out a drug-drug interaction (DDI) is critical to this extent as the presence of a 
DDI would translate into reduced or abolished antiplatelet effects exposing these acute patients 
to an increased thrombotic risk. Despite the available evidence suggesting a lack of DDI with the 
use of ticagrelor in cangrelor treated patients, most data derive from studies in which ticagrelor 
was given at the time of initiation or during cangrelor infusion. To date, there is no data to fully 
rule out a DDI when ticagrelor is given prior to starting cangrelor infusion. The need for such 
investigation is underscored by the relatively high prevalence of pretreatment with ticagrelor in 
acute settings. The methodological approach for this assessment should rely on comprehensive 
pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, 
pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and 
mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The 
overarching aim of this investigation is to rule out a DDI when ticagrelor is administered prior to 
cangrelor infusion. 
 


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BACKGROUND 
Cangrelor is an intravenous adenosine triphosphate (ATP) analogue that directly and 
reversibly inhibits ADP binding to the adenosine diphosphate (ADP) P2Y12 receptor subtype in a 
dose-dependent manner, achieving immediate potent platelet inhibition after a bolus dose [1,2]. 
The cangrelor binding site at the P2Y12 receptor level has been subject to controversy and is not 
clearly defined [3,4]. Nonetheless, cangrelor is associated with high levels of receptor occupancy 
and prevents ADP binding. Cangrelor is promptly inactivated through dephosphorylation by 
ectonucleotidase and has a very short plasma half-life (3-6 minutes) [1-4]. Therefore, recovery of 
platelet function is rapid (~60 minutes) after discontinuation of cangrelor infusion [1-4].  
Cangrelor was approved for clinical use based on the results of the CHAMPION 
(Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) 
PHOENIX trial, which showed that cangrelor significantly reduced the rate of ischemic events, 
driven by a reduction in stent thrombosis and myocardial infarction, with no significant increase 
in severe bleeding in patients undergoing percutaneous coronary intervention (PCI) [5]. Given 
the different pharmacological properties of cangrelor and the oral P2Y12 inhibitors, several 
studies have investigated the potential for drug-drug interaction (DDI) when these agents are 
concomitantly administered [6-12]. These potential DDIs are concerning as they can result in 
reduced platelet inhibition and subsequent lack of protection from thrombotic complications in 
the peri-PCI period. In a study conducted in healthy volunteers, clopidogrel administration 
during cangrelor infusion was associated with an impaired antiplatelet effect of clopidogrel after 
cangrelor discontinuation [6]. This reflects the fact that clopidogrel active metabolite cannot bind 
to the P2Y12 receptors if already largely occupied by cangrelor. In turn, the plasma 
concentrations of the unbound clopidogrel active metabolites fall rapidly to subtherapeutic levels 


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as a result of distribution to other compartments and systemic clearance. Therefore, after 
stopping cangrelor infusion, when receptors become available for binding, most of the active 
metabolite has already been eliminated from the circulation [6]. In contradistinction, 
clopidogrel’s antiplatelet effects are not diminished when it is administered after cangrelor 
infusion, because of the very fast offset of action of cangrelor and subsequent availability of 
P2Y12 receptors for binding by clopidogrel active metabolite [6]. Accordingly, across the 
CHAMPION clinical trial program, a clopidogrel loading dose (LD) was administered always 
immediately after discontinuation of cangrelor infusion [5,13-15]. 
Although cangrelor was approved based on a trial in which clopidogrel was used, in real-
world clinical practice cangrelor is more commonly utilized in high-risk patients undergoing 
PCI, in particular patients with acute coronary syndromes (ACS), in whom the newer generation 
P2Y12 inhibitors (i.e, prasugrel and ticagrelor) are recommended over clopidogrel [16-17]. 
Recommendations on how to transition from cangrelor to oral treatment with ticagrelor and 
prasugrel largely derive from pharmacodynamic (PD) studies [3,4,8,9]. Unlike that observed 
with clopidogrel, no interaction was shown when transitioning from cangrelor to ticagrelor, 
allowing for a more versatile use of ticagrelor with respect to timing of administration in relation 
to the start of cangrelor therapy [8]. The presence of an interaction between clopidogrel and 
cangrelor, but not between ticagrelor and cangrelor is probably the result of different half-lives 
of these drugs, as well as the different sites and types of binding to the P2Y12 receptor [3,4,6-
8,11,12].  
Ticagrelor reversibly binds the P2Y12 receptor at a site distinct from the ADP-binding site 
and has a half-life of 6-12 hours. Although it is unknown whether ticagrelor can bind with the 
P2Y12 receptor during cangrelor infusion, its half-life is such that drug is still systemically 


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available to bind with the P2Y12 receptor after discontinuation of cangrelor infusion [3,4,8]. This 
was most recently demonstrated in the CANTIC (The Platelet Inhibition with CANgrelor and 
Crushed TICagrelor in STEMI Patients Undergoing Primary Percutaneous Coronary 
Intervention) study, which was the first study to rule out a DDI in the setting of patients 
presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary 
intervention, in which ticagrelor, administered as a crushed formulation, was given 
concomitantly with cangrelor without any apparent DDI [18]. Overall, based on these PD 
observations, according to FDA product label, ticagrelor can be administered at any time during 
cangrelor infusion or immediately after discontinuation [19]. 
 
STUDY RATIONALE 
Despite the available evidence suggesting a lack of DDI with the use of ticagrelor in 
cangrelor treated patients, most data derive from studies in which ticagrelor was given at the time 
of initiation or during cangrelor infusion. To date there is no data to fully rule out a DDI when 
ticagrelor is given prior to starting cangrelor infusion. In fact, although a prior PD investigation 
demonstrated that ticagrelor given before cangrelor did not attenuate the PD effects of cangrelor, 
this study did not assess whether the PD effects of ticagrelor are preserved after discontinuing 
cangrelor infusion [8]. In another investigation, PD effects were studied in patients pretreated 
with ticagrelor with less than 1 hour from primary PCI or receiving ticagrelor in cath lab and 
treated with cangrelor [20]. At 30 min after end of infusion, platelet reactivity was within the 
therapeutic range for most patients and there were no differences between patients treated with 
ticagrelor prehospital or in the cath lab. Thus, the design of this study cannot rule-out a DDI due 
to several factors: the comparison was not randomized, at 30 min there is still residual effect of 


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cangrelor which warrants at least 60 minutes for complete wash-out of effects (thus not adequate 
to rule out a DDI), and 12.5% of patients had high platelet reactivity at this time point [20]. 
Moreover, in none of the above mentioned studies were pharmacokinetic (PK) assessments 
performed to characterize the impact, if any, of cangrelor on systemic levels of ticagrelor and its 
major metabolite (AR-C124910XX). Therefore, the lack of data to rule out a DDI between 
cangrelor and ticagrelor when the latter is administered prior to starting cangrelor infusion 
warrants dedicated prospective investigations. The need for such investigations is underscored by 
the relatively high prevalence of pretreatment with ticagrelor in acute settings [21,22]. 
Importantly, such acute settings represent desirable scenarios to use cangrelor. Of note, use of 
prehospital ticagrelor (i.e, pretreatment) in acute settings is endorsed by practice guidelines both 
in the United States and Europe [17]. Therefore, ruling out a DDI between cangrelor and 
ticagrelor when the latter is administered prior to starting cangrelor infusion would have 
important clinical implications for real-world practice. The methodological approach for this 
assessment should rely on comprehensive PD assessments aimed to evaluate levels of P2Y12 
receptor inhibition and thrombus formation, PK assessments to assess systemic levels of the 
drug/drug metabolite, and mechanistic assessments by measuring levels of P2Y12 receptor gene 
expression. In particular, different levels of P2Y12 receptor gene expression can modulate the PD 
effects of oral P2Y12 receptor inhibitors at a given level of drug exposure defined by PK 
profiling. 
 
 
 
 


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STUDY AIM 
The aim of this investigation is to rule out a DDI when ticagrelor is administered prior to 
cangrelor infusion. Comprehensive PK and PD assessments will be conducted to reach this study 
aim. 
 
REASERCH PLAN 
Study design 
The Switching Antiplatelet Therapy-5 (SWAP-5) study will be a prospective, 
randomized, double-blind, placebo controlled, cross-over PK and PD investigation aimed to rule 
out a DDI when ticagrelor is administered prior to cangrelor infusion. Aspirin treated patients 
with known coronary artery disease will be considered eligible for the study. The study will be 
performed at the Division of Cardiology of University of Florida Health, Jacksonville, Florida. 
Patients will be screened by Cardiology Research staff, who will verify that all candidates meet 
inclusion and exclusion criteria, and obtain their written informed consent to participate in the 
study. Results from blood tests performed within the last 90 days will be considered valid for 
screening purposes. If these are not available, a blood sample will be collected for the screening 
phase. 
Using a computer-based randomization system, patients will be randomized in a 1:1 
fashion to one of the following treatment arms: a) ticagrelor loading dose followed after 1 hour 
by cangrelor bolus and infusion or b) ticagrelor loading followed after 1 hour by placebo 
infusion. In line with FDA recommendations, ticagrelor will be administered as a 180mg loading 
dose (two 90mg tablets) [23]. Cangrelor will be used at the FDA recommended dose using a 30 
μg/kg bolus followed by 4 μg/kg/min infusion [19]. The duration of cangrelor/placebo infusion 


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will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week 
wash-out period and then will cross-over to the alternative treatment in the second phase (i.e., 
patients assigned to treatment with cangrelor in the first phase will be assigned to placebo in the 
second phase and vice-versa). All patients will be on a background of aspirin therapy (81 mg 
daily maintenance dose). During each phase, PK and PD assessments will be conducted at 7 time 
points (total 14 time points): baseline (prior to ticagrelor loading dose; time -1 h); at start of 
cangrelor/placebo bolus and infusion (1 hour after ticagrelor loading dose); 30 minutes after 
cangrelor/placebo bolus; 1 hour after cangrelor/placebo bolus, 2 hours after cangrelor/placebo 
bolus (time of infusion discontinuation); 1 hour after discontinuation of cangrelor/placebo 
infusion; and 2 hours after after discontinuation of cangrelor/placebo infusion. Figure 1 
illustrates the overall study design. The study will have a double-blind design. Patients, research 
staff and laboratory personnel will be blinded to treatment assignments. Masking and 
randomization of medications (cangrelor and placebo) will be performed by our institutional 
research pharmacy in line with prior investigations [18]. 
Figure 1. Overall study design 
 
 
 
 
 
 
 
 
Washout  
& 
Crossover 
(1-4 weeks) 


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Study Population 
Inclusion criteria: 
• Patients with known coronary artery disease (defined as prior type I myocardial 
infarction, coronary revascularization, percutaneous or surgical, or presence of at least a 
50% stenosis in any major epicardial vessel). 
• Age > 18 years old 
• On aspirin 81mg/qd for at least 1 month 
 
Exclusion criteria:        
• Inability to provide written informed consent 
• Hemodynamic instability 
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, 
ticagrelor) in past 30 days  
• Known allergies to ticagrelor or cangrelor 
• Considered at high risk for bleeding 
• History of intracranial bleeding/hemorrhagic stroke 
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, 
apixaban, edoxoban) within past 30 days 
• Known platelet count <80x106/mL 
• Known hemoglobin <10 g/dL 
• Active bleeding 
• Known end stage renal disease on hemodialysis 
• Known severe hepatic dysfunction 
• Acute or severe bronchial asthma or upper airway obstruction. 
• Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker 
protection. 
• Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction 
with ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, 
ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin. 


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• Pregnant females [women of childbearing age must use reliable birth control (i.e. oral 
contraceptives) while participating in the study] 
 
Blood sampling and Laboratory assessments 
Blood samples (10 mL) will be drawn through a short venous catheter inserted into a 
forearm vein and collected in anticoagulated and serum tubes at each study time point for all 
PK/PD assessments. The first 2-4 mL of blood will be discarded to avoid spontaneous platelet 
activation. 
 
Laboratory assessments will include: 
1. VerifyNow PRU 
2. Light transmittance aggregometry 
3. Whole blood vasodilator-stimulated phosphoprotein (VASP) 
4. Total Thrombus-Formation Analysis System (T-TAS) 
5. PK 
6. P2Y12 gene receptor level expression 
 
Description of laboratory assays 
1) VerifyNow PRU: The VerifyNow System is a turbidimetric based optical detection system 
which measures platelet induced aggregation as an increase in light transmittance (Accriva, San 
Diego, CA) and will be utilized according to manufacturer’s instructions, as previously described 
[18, 24-26]. The assay is based on microbead agglutination and uses specific reagents for the 
pathways of interest. The VerifyNow PRU assay, by combining ADP+PGE1, measures changes 
in platelet function specific to P2Y12 receptor inhibitors. The assay is based upon the ability of 


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activated platelets to bind fibrinogen. Fibrinogen-coated microparticles aggregate in proportion 
to the number of GP IIb/IIIa receptors expressed. Microbead aggregation is more rapid and 
reproducible if platelets are activated; therefore the reagents are incorporated into the assay 
channel to induce platelet activation without fibrin formation. Light transmittance increases as 
activated platelets bind and aggregate fibrinogen-coated beads. The instrument measures this 
change in optical signal and reports results in P2Y12 Reaction Units (PRU). 
2) Light transmittance aggregometry (LTA): Platelet aggregation will be performed using LTA 
according to standard protocols. Blood will be collected in citrated (3.2%) tubes. LTA will be 
performed using platelet rich plasma (PRP) by the turbidimetric method in a 2-channel 
aggregometer (Chrono-Log 490 Model, Chrono-Log Corp., Havertown) as previously described 
[24-26]. Platelet agonists will include collagen (3µg/ml), ADP (20 µM) and TRAP (15 μM). PRP 
will be obtained as a supernatant after centrifugation of citrated blood at 1000 rpm for 10 
minutes. The isolated PRP will be kept at 37° C before use. Platelet poor plasma (PPP) will be 
obtained by a second centrifugation of the blood fraction at 2800 rpm for 10 minutes. Light 
transmission will be adjusted to 0% with the PRP and to 100% for the PPP for each 
measurement. Curves will be recorded for 6 minutes and platelet aggregation will be determined 
as the maximal percent change (MPA) in light transmittance from baseline using PPP as a 
reference.   
3) Whole blood vasodilator-stimulated phosphoprotein (VASP):  VASP phosphorylation (VASP-
P) is a marker of P2Y12 receptor signaling. VASP will be assessed the ELISA VASP-P kit 
(Biocytex Inc., Marseille, France) as previously described [18]. After a first step of parallel 
whole blood sample activation with PGE1 and PGE1+ADP, platelets from the sample are lysed, 
allowing released VASP to be captured by an anti-human VASP antibody, which is coated in the 


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microtiter plate. Then, a peroxidase-coupled anti-human VASP-P antibody binds to 
phosphorylated serine 239 antigenic determinant of VASP. The bound enzyme peroxidase is 
then revealed by its activity on TMB substrate over a predetermined time. After stopping the 
reaction, absorbance at 450 nm is directly related to the concentration of VASP-P contained in 
the sample.PGE1 increases VASP-P levels by stimulation of adenylate cyclase. Binding of ADP 
to P2Y12 leads to Gi-coupled inhibition of adenylate cyclase. Therefore, the addition of ADP to 
PGE1-stimulated platelets reduces PGE1-induced VASP-P levels. If P2Y12 receptors are 
successfully inhibited, addition of ADP will not reduce the PGE1-stimulated VASP-P levels. The 
platelet reactivity index (PRI) will be calculated after measuring VASP-P levels. 
4) Total Thrombus-Formation Analysis System (T-TAS): T-TAS is an automated microchip flow 
chamber system for the quantitative analysis of the thrombus formation process under blood flow 
conditions. T-TAS allows measurement of thrombus formation using the PL-chip (Diapharma, 
West Chester Township, OH) [27]. The PL-chip contains 25 capillary channels (width 40 μm, 
depth 40 μm) coated with type I collagen and is specifically designed for quantitative analysis of 
platelet thrombus formation, including platelet adhesion and aggregation, granule secretion, and 
thrombus growth in the absence of coagulation and fibrinolysis systems. In measurements using 
the PL-chip, a blood sample collected in a hirudin containing blood sampling tube. The platelet 
aggregates gradually increase in size and, in the process, occlude the capillary, resulting in an 
increase in flow pressure. In the present study, total platelet-derived thrombogenicity is 
expressed as the area under the flow pressure curve for the first 10 min for the PL-chip tested at a 
flow rate of 18 μL/min (PL18-AUC10). Low PL18-AUC10 reflect reduced thrombus growth and 
rapid breakdown of the thrombus. 


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4) Pharmacokinetic (PK) assay: Determination of plasma concentration of ticagrelor and its 
active metabolite (AR-C124910XX) will be assessed from blood samples taken at the same time 
points of PD analysis as previously described [28]. Blood samples for measurement of drug 
concentrations will be drawn through the same cannula used for PD sampling. The blood will be 
taken into lithium heparin tubes and placed on ice until centrifugation (2800 rpm, 4°C, 10 min) 
within 30 min of sampling to collect the plasma, which will be transferred to plain polypropylene 
tubes and frozen upright at or below -20°C until analysis. For ticagrelor and its active metabolite, 
the area under the plasma concentration vs. time curve from time 0 to the last measurable 
concentration (AUC0-t), maximum plasma concentration (Cmax), and time to Cmax (tmax) will 
be estimated. 
5) P2Y12 gene receptor level expression: Gene expression in platelets will be performed using 
standard protocols. In particular, purified platelets are dissolved in Trizol reagent (Invitrogen) 
and total RNA will be extracted using RNA minipres kit (Zymos research) according to 
manufacturer’s protocol.  P2Y12 mRNA expression will be measured with real-time PCR using 
SYBR green and specific primers as previously described [29].   
 
In addition to specific assays described above, whole blood, serum and plasma samples will be 
stored for future analysis that may include genetic determinants of antiplatelet drugs response, 
alternative mRNAs, and biomarkers.  
 
Study endpoints, sample size calculation and statistical analysis 
 
The primary end point of the study will be the non-inferiority in PRU measured at 2 
hours after discontinuation of cangrelor vs. placebo. We hypothesize that in patient receiving 


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cangrelor following a ticagrelor LD platelet inhibition assessed by PRU will be non-inferior 
compared to patients receiving ticagrelor LD followed by placebo infusion. Non-inferiority will 
be assessed using a 95% confidence interval (CI) of the difference in mean PRU between the two 
arms. Under the assumption of 0 difference in mean PRU between group 1 and group 2 and a 
common standard deviation of 75 PRU, a sample size of 16 patients will allow for the 95% CI to 
stay within ± 45 PRU with a 95% power and alpha=0.05. Considering a 25% data attrition rate 
due to hemolysis, drop out or technical problems, 20 patients will need to be randomized in order 
to ensure complete available data for analysis. The sample size of this study was established 
according to results of previous PD investigations [18,30]. In line with previously reported 
investigations, 45 PRU was chosen for the noninferiority margin for the upper 95% CI limit of 
the difference [25, 31]. All other end points will be considered exploratory and will include the 
comparisons of PD and PK parameters, and P2Y12 gene receptor level expression between all 
treatment arms at each time points, as well as the comparisons of rates of high on-treatment 
platelet reactivity (HPR). HPR will be defined as PRU>208, PRI>50%, and LTA-ADP>59%, in 
line with consensus definitions [32].  
Conformity to the normal distribution will be evaluated for continuous variables with the 
Kolmogorov-Smirnov test. For baseline characteristics, continuous variables will be expressed as 
mean ± SD or median [IQR]. Treatment effects will be evaluated comparing the functional 
parameters observed in the overall patient population after cangrelor treatment with those 
achieved after placebo regardless of the sequence. All statistical comparisons of platelet function 
for the primary end point and exploratory end points with continuous variables will be conducted 
using a linear mixed-effect model with treatment group, sequence, period, and treatment-group-
by-period as fixed effects, patient as a random effect, and baseline value of the corresponding 


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platelet function test as a covariate. The comparisons of rates of HPR will be conducted using the 
McNemar test. 
Platelet reactivity results will be reported as least-square means (LSM) (95% confidence 
interval [CI]) for the above detailed analyses. LSM differences in PRU between groups and the 
corresponding 2-sided 95% CI for the difference will be obtained to assess non-inferiority based 
on the linear model. Given the exploratory nature of comparisons for secondary end points, 
correction for multiple comparisons will not be performed. A 2-tailed p value of <0.05 will be 
considered to indicate a statistically significant difference for superiority for all the analyses 
performed. Statistical analysis will be performed using SPSS version 25.0 software (SPSS Inc., 
Chicago, Illinois).  
The safety population will include all randomized patients exposed to study medication. 
The PD population will include all patients with PD data and without a major protocol deviation 
thought to affect significantly the PD and PK of cangrelor or ticagrelor. The PD population will 
be used for analysis of all primary and secondary end points. Erroneously treated patients (eg, 
those randomized to one treatment but actually given the other) will be accounted for based on 
the actual treatment received. 
 
Publication Strategy/Additional Information  
Subjects will be identified with a number and data collection sheets will all be stored in a 
locked area. Data will be kept for 6 years after enrollment ends to comply with HIPAA 
regulations. Patients will receive a handout with the names and telephone numbers of the doctors 
involved in the study. Study subjects will be identified first (months 1-8): we expect to 
randomize 2-3 subjects monthly and complete enrollment in 8 months (total: 20 subjects 


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randomized). Months 9 and 10 will be implied for statistical analysis and manuscript preparation. 
Results will be presented at the first available major cardiovascular meeting (e.g. AHA, ACC, 
ESC), and final manuscript will be submitted to publication to one of major cardiovascular 
journals (e.g. JACC, Circulation, European Heart Journal). 
 
Possible Discomforts and Risk 
In clinical trials, the most common clinical side effect of cangrelor was bleeding. 
Severe/moderate bleeding occurred in 0.8% of patients receiving cangrelor, as compared to 0.6% 
of those receiving placebo; other side effects include dyspnea (1.3%), worsening renal function 
(3.2% of patients with severe renal impairment), and hypersensitivity (0.05%) [5]. In clinical 
trials, the most common clinical side effects of ticagrelor were dyspnea (13.8%), headache 
(6.5%), cough (4.9%), dizziness (4.5%), nausea (4.3%), and bradycardia (4.4%) principally. 
Infrequent events included intracranial hemorrhage (0.3%) and severe bradycardia requiring 
pacemaker insertion (0.9%) [33]. The most important adverse effect associated with the use of 
ticagrelor is bleeding. The risk of spontaneous bleeding with ticagrelor is 2.8% [32]. However, 
such bleeding prevalence occurred in the setting of a long-term (12 months) trial, while our study 
is limited to a single loading dose, thus reducing the risk of any side effect, in particular bleeding 
complications.  
All clinical events described above, if they were to occur, as well as death, myocardial 
infarction, stroke, and urgent revascularization procedure with PCI or coronary artery bypass 
grafting will be recorded. Bleeding data will be collected using BARC definitions [34]. Clinical 
events will be evaluated by a local committee, comprised of 2 faculty members (2 cardiologists), 
not directly involved in the research. In the event of a report of a serious adverse event the local 


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committee will meet and antiplatelet treatment management will be managed according to 
physician recommendation. 
 
Conflict of Interest 
Dr. Franchi (Principal Investigator) is a paid consultant for AstraZeneca pharmaceutical the 
maker of Ticagrelor, which is used in the study. Dr. Angiolillo (Sub-Investigator) is a consultant 
for Chiesi, the maker of cangrelor, and of AstraZeneca, the maker of ticagrelor 
 
 


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References 
1. Franchi F, Rollini F, Muñiz-Lozano A, Cho JR, Angiolillo DJ. Cangrelor: a review on 
pharmacology and clinical trial development. Expert Rev Cardiovasc Ther. 
2013;11:1279-91.  
2. Angiolillo DJ, Schneider DJ, Bhatt DL, French WJ, Price MJ, Saucedo JF, Shaburishvili 
T, Huber K, Prats J, Liu T, Harrington RA, Becker RC. Pharmacodynamic effects of 
cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus 
standard therapy to achieve optimal management of platelet inhibition (CHAMPION) 
trials. J Thromb Thrombolysis. 2012;34:44-55.  
3. Angiolillo DJ, Rollini F, Storey RF, Bhatt DL, James S, Schneider DJ, Sibbing D, So 
DYF, Trenk D, Alexopoulos D, Gurbel PA, Hochholzer W, De Luca L, Bonello L, Aradi 
D, Cuisset T, Tantry US, Wang TY, Valgimigli M, Waksman R, Mehran R, Montalescot 
G, Franchi F, Price MJ. International Expert Consensus on Switching Platelet P2Y(12) 
Receptor-Inhibiting Therapies. Circulation. 2017136:1955-1975.  
4. Rollini F, Franchi F, Angiolillo DJ. Switching P2Y12-receptor inhibitors inpatients with 
coronary artery disease. Nat Rev Cardiol. 2016;13:11-27. 
5. Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, Price MJ, 
Leonardi S, Gallup D, Bramucci E, Radke PW, Widimský P, Tousek F, Tauth J, Spriggs 
D, McLaurin BT, Angiolillo DJ, Généreux P, Liu T, Prats J, Todd M, Skerjanec S, White 
HD, Harrington RA; CHAMPION PHOENIX Investigators. Effect of platelet inhibition 
with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368:1303-13. 
6. Steinhubl SR, Oh JJ, Oestreich JH, Ferraris S, Charnigo R, Akers WS. Transitioning 
patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive 
effect. Thromb Res. 2008;121:527-34. 
7. Schneider DJ, Agarwal Z, Seecheran N, Gogo P. Pharmacodynamic effects when 
clopidogrel is given before cangrelor discontinuation. J Interv Cardiol 2015;28:415-9. 
8. Schneider DJ, Agarwal Z, Seecheran N, Keating FK, Gogo P. Pharmacodynamic effects 
during the transition between cangrelor and ticagrelor. JACC Cardiovasc Interv 
2014;7:435-42. 
9. Schneider DJ, Seecheran N, Raza SS, Keating FK, Gogo P. Pharmacodynamic effects 
during the transition between cangrelor and prasugrel. Coron Artery Dis. 2015;26:42-8.  


Version 1.  
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19 
 
10. Schneider DJ. Transition strategies from cangrelor to oral platelet P2Y12 receptor 
antagonists. Coron Artery Dis. 2016;27:65-9. 
11. Dovlatova NL, Jakubowski JA, Sugidachi A, Heptinstall S. The reversible P2Y 
antagonist cangrelor influences the ability of the active metabolites of clopidogrel and 
prasugrel to produce irreversible inhibition of platelet function. J Thromb Haemost. 
2008;6:1153-9. 
12. Judge HM, Buckland RJ, Jakubowski JA, Storey RF. Cangrelor inhibits the binding of 
the active metabolites of clopidogrel and prasugrel to P2Y12 receptors in vitro. Platelets. 
2016;27:191-5. 
13. Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, Kleiman 
NS, Goodman SG, White HD, Mahaffey KW, Pollack CV Jr, Manoukian SV, Widimsky 
P, Chew DP, Cura F, Manukov I, Tousek F, Jafar MZ, Arneja J, Skerjanec S, Harrington 
RA; CHAMPION PLATFORM Investigators. Intravenous platelet blockade with 
cangrelor during PCI. N Engl J Med. 2009;361:2330-41. 
14. Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, Pollack CV 
Jr, Montalescot G, Mahaffey KW, Kleiman NS, Goodman SG, Amine M, Angiolillo DJ, 
Becker RC, Chew DP, French WJ, Leisch F, Parikh KH, Skerjanec S, Bhatt DL. Platelet 
inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009;361:2318-29. 
15. Steg PG, Bhatt DL, Hamm CW, Stone GW, Gibson CM, Mahaffey KW, Leonardi S, Liu  
T, Skerjanec S, Day JR, Iwaoka RS, Stuckey TD, Gogia HS, Gruberg L, French WJ, 
White HD, Harrington RA; CHAMPION Investigators. Effect of cangrelor on 
periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of 
patient-level data. Lancet. 2013;382:1981-92. 
16. Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev 
Cardiol 2015;12:30-47. 
17. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/AHA Versus 
ESC Guidelines on Dual Antiplatelet Therapy: JACC Guideline Comparison. J Am Coll 
Cardiol 2018;72:2915-31. 
18. Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, 
Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni 
MM, Bass TA, Angiolillo DJ. Platelet Inhibition with Cangrelor and Crushed Ticagrelor 


Version 1.  
November 9, 2020 
 
20 
 
in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous 
Coronary Intervention: Results of the CANTIC Study. Circulation 2019;139:1661-70. 
19. Cangrelor United States full prescribing information [online], 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204958lbl.pdf [Accessed 
April 2019] 
20. Mohammad MA, Andell P, Koul S, James S, Scherstén F, Götberg M, Erlinge D. 
Cangrelor in combination with ticagrelor provides consistent and potent P2Y12-
inhibition during and after primary percutaneous coronary intervention in real-world 
patients with ST-segment-elevation myocardial infarction. Platelets. 2017;28:414-416. 
21. Redfors B, Dworeck C, Haraldsson I, Angerås O, Odenstedt J, Ioanes D, Petursson P, 
Völz S, Albertsson P, Råmunddal T, Persson J, Koul S, Erlinge D, Omerovic E. 
Pretreatment with P2Y12 receptor antagonists in ST-elevation myocardial infarction: a 
report from the Swedish Coronary Angiography and Angioplasty Registry. Eur Heart J. 
2019;40:1202-1210. 
22. Fan W, Plent S, Prats J, Deliargyris EN. Trends in P2Y12 Inhibitor Use in Patients 
Referred for Invasive Evaluation of Coronary Artery Disease in Contemporary US 
Practice. Am J Cardiol. 2016;117:1439-43. 
23. FDA ticagrelor label package: 
www.accessdata.fda.gov/drugsatfda_docs/label/2013/022433s010lbl.pdf  Accessed on 
April 2019. 
24. Angiolillo DJ, Badimon JJ, Saucedo JF, Frelinger AL, Michelson AD, Jakubowski JA, 
Zhu B, Ojeh CK, Baker BA, Effron MB. A pharmacodynamic comparison of prasugrel 
vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery 
disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS 
(OPTIMUS)-3 Trial. Eur Heart J. 2011:838-46. 
25. Angiolillo DJ, Curzen N, Gurbel P, Vaitkus P, Lipkin F, Li W, Jakubowski JA, Zettler 
M, Effron MB, Trenk D. Pharmacodynamic evaluation of switching from ticagrelor to 
prasugrel in patients with stable coronary artery disease: Results of the SWAP-2 Study 
(Switching Anti Platelet-2). J Am Coll Cardiol. 2014 Apr 22;63(15):1500-9. 
26. Franchi F, Faz GT, Rollini F, Park Y, Cho JR, Thano E, Hu J, Kureti M, Aggarwal N, 
Durairaj A, Been L, Zenni MM, Guzman LA, Suryadevara S, Antoun P, Bass TA, 


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November 9, 2020 
 
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Angiolillo DJ. Pharmacodynamic Effects of Switching From Prasugrel to Ticagrelor: 
Results of the Prospective, Randomized SWAP-3 Study. JACC Cardiovasc Interv. 
2016;9:1089-98.  
27. Kikuchi S, Tsukahara K, Ichikawa S, Abe T, Minamimoto Y, Kimura Y, Akiyama E, 
Nakayama N, Okada K, Matsuzawa Y, Konishi M, Maejima N, Iwahashi N, Hibi K, 
Kosuge M, Ebina T, Tamura K, Kimura K. Platelet-Derived Thrombogenicity Measured 
by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation 
Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.  Circ J. 
2020;84:975-984. 
28. Franchi F, Rollini F, Cho JR, Bhatti M, DeGroat C, Ferrante E, Dunn EC, Nanavati A, 
Carraway E, Suryadevara S, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Impact of 
Escalating Loading Dose Regimens of Ticagrelor in Patients With ST-Segment Elevation 
Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results 
of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation. 
JACC Cardiovasc Interv. 2015;8:1457-67. 
29. Hu L, Chang L, Zhang Y, Zhai L, Zhang S, Qi Z, Yan H, Yan Y, Luo X, Zhang S, Wang 
Y, Kunapuli SP, Ye H, Ding Z. Platelets Express Activated P2Y12 Receptor in Patients 
With Diabetes Mellitus. Circulation. 2017;136:817-833. 
30. Franchi F, Rollini F, Park Y, Hu J, Kureti M, Rivas J, Mewa J, Faz G, Yaranov D, Been 
L, Antoun P, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Effect of the Peripheral 
Opioid Receptor Antagonist Methylnaltrexone on the Pharmacokinetic and 
Pharmacodynamic Profiles of Ticagrelor in Patients Receiving Morphine: A Prospective 
Randomized Placebo-Controlled Trial. Circulation 2016; 134:A19115. 
31. Franchi F, Rollini F, Rivas Rios J, Rivas A, Agarwal M, Kureti M, Nagaraju D, Wali M, 
Shaikh Z, Briceno M, Nawaz A, Moon JY, Been L, Suryadevara S, Soffer D, Zenni MM, 
Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Switching From Ticagrelor to 
Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study. 
Circulation. 2018;137:2450-2462. 
32. Tantry US, Bonello L, Aradi D, Price MJ, Jeong YH, Angiolillo DJ, Stone GW, Curzen 
N, Geisler T, Ten Berg J, Kirtane A, Siller-Matula J, Mahla E, Becker RC, Bhatt DL, 
Waksman R, Rao SV, Alexopoulos D, Marcucci R, Reny JL, Trenk D, Sibbing D, Gurbel 


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PA; Working Group on On-Treatment Platelet Reactivity. Consensus and update on the 
definition of on-treatment platelet reactivity to adenosine diphosphate associated with 
ischemia and bleeding. J Am Coll Cardiol 2013;62:2261-73. 
33. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, 
Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, 
Harrington RA; PLATO Investigators. Ticagrelor versus clopidogrel in patients with 
acute coronary syndromes. N Engl J Med. 2009; 361:1045-57 
34. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, 
Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, 
Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding 
definitions for cardiovascular clinical trials: a consensus report from the Bleeding 
Academic Research Consortium. Circulation. 2011;123:2736-47. 
 

ICF_001.pdf: 
IRB APPROVED 
Dec 10, 2020 
 
 
1 
 
 
University of Florida – Jacksonville 
 
SUBJECT INFORMATION AND CONSENT FORM 
 
TITLE: 
Pharmacodynamic and pharmacokinetic profiles of switching 
between cangrelor and ticagrelor following ticagrelor pre-
treatment: The Switching Antiplatelet -5 (SWAP-5) study 
 
PROTOCOL NO.: 
SWAP-5  
IRB Protocol #20203948 
 
SPONSOR: 
University of Florida 
 
INVESTIGATOR: 
Francesco Franchi, MD 
 
655 West 8th Street 
 
Jacksonville, Florida 32209 
 
United States 
 
STUDY-RELATED 
PHONE NUMBER(S): 
Francesco Franchi, MD 
 
904-244-2060 
 
904-244-0411 (24 hours) 
 
 
Name of person seeking your consent: ___________________________________________ 
 
 
Place of employment & position: _________________________________________________ 
 
 
Name of Participant (“Study Subject”) 
 
______________________________________________________________________________ 
 


IRB APPROVED 
Dec 10, 2020 
 
 
2 
In general, what do you need to know about this Research Study? 
 
The purpose of this form is to seek your consent to participate in research. 
 
Agreeing to become involved in any research is always voluntary.  By signing this form, you are 
not waiving any of your legal rights. If you decide not to participate in this research, you will not 
be penalized in any way and you will not lose any benefits to which you are entitled. If you have 
questions about your rights as a research subject, please call the University of Florida Institutional 
Review Board (IRB) office at (352) 273-9600. 
a) In general, what is the purpose of the research, how long will you be involved? The 
purpose of this study is to rule out that there would be a drug to drug interaction when 
Ticagrelor is given before a Cangrelor infusion 
b) What is involved with your participation, and what are the procedures to be followed in the 
research? Your involvement will require receiving a dose of Ticagrelor and an infusion of 
Cangrelor or placebo along with 7 blood draws at different time points. This will occur 
twice at two different visits. 
c) What are the likely risks or discomforts to you? There are risks of pain or discomfort from 
the blood draw, and there are risks to all the medications, which are discussed in detail 
below.  
d) What are the likely benefits to you or to others from the research? There is no guarantee of 
direct benefit.  
e) What are the appropriate alternative procedures or courses of treatment, if any, that might 
be helpful to you? The alternative is to not participate.  
 
Additional and more detailed information is provided within the remainder of this Informed 
Consent form, please read before deciding if you wish to participate in this study 
 
This consent form may contain words that you do not understand. Please ask the study doctor or 
the study staff to explain any words or information that you do not clearly understand. 
 
WHAT WILL BE DONE AS PART OF YOUR NORMAL CLINICAL CARE (EVEN IF 
YOU DID NOT PARTICIPATE IN THIS RESEARCH STUDY)? 
If you choose not to participate in this study, you will be treated and followed by your primary 
care team per normal standard of care. 
 
WHY IS THIS RESEARCH STUDY BEING DONE? 
You are being asked to participate in this study because you have coronary artery disease for 
which you are taking aspirin. You must be informed so you can decide whether you want to 
participate. 
 
Platelets are parts of your blood that stick together to help form a clot. The stickier your platelets 
are, the greater your chances of having heart attacks or strokes. Platelets from patients with heart 
disease tend to stick together more, increasing the risk of having a heart attack or stroke. To 
prevent a heart attack, there are antiplatelet drugs (blood thinners) to keep your platelets from 
sticking together. Ticagrelor (Brilinta), is one of the oral antiplatelet drugs used in the treatment 
of patients with coronary artery disease like yours and are typically used in association with baby 
aspirin.  
 


IRB APPROVED 
Dec 10, 2020 
 
 
3 
For patients who are suffering from a heart attack and require a stent, it is likely the doctor would 
give the patient Ticagrelor after a stent has been placed. However, ticagrelor is sometimes 
administered immediately at hospital presentation before the procedure. The doctor might also 
use another blood thinning medication called Cangrelor during the stent procedure, which is 
given through an IV. Cangrelor is used during the procedure to potentiate the blood thinning 
effects and can be administered before or at the same time of ticagrelor. However, there have 
been no studies that test how cangrelor and ticagrelor work in patients that receive cangrelor 
after have already received Ticagrelor.  
 
The purpose of this pilot study is to test the presence of drug to drug interactions when adding 
Cangrelor to patients already on Ticagrelor. For this study we will be looking at patients who are 
not currently having a heart attack or on any blood thinning medications, besides aspirin.  The 
results of this pilot study will help inform if it is therefore safe to treat patients who are having a 
heart attack with Cangrelor if they have already received Ticagrelor.  Cangrelor is approved by 
the FDA for patients undergoing coronary artery stenting; however, as used in this research 
study, it is considered investigational.  
 
HOW MANY PEOPLE ARE EXPECTED TO TAKE PART IN THIS RESEARCH 
STUDY? 
Up to 30 people are expected to take part in this study. 
 
HOW LONG WILL YOU BE IN THIS RESEARCH STUDY? 
If you are eligible, you will be expected to take part in the research for up to 33 days. 
 
WHO CAN PARTICIPATE IN THIS STUDY? 
Your study doctor will determine if you are able to participate in this research study. Please feel 
free to ask the study doctor about the study requirements for participation. 
 
WHAT WILL BE DONE ONLY BECAUSE YOU ARE IN THIS RESEARCH STUDY? 
Your study doctor will fully explain the study, other possible treatments, and any known or 
possible side effects of participating in this study. If you consent to participate in this study, your 
study doctor will collect data from your medical records. You will be evaluated to see if you 
meet criteria to enter into the research protocol. If you are a woman of childbearing potential, a 
pregnancy test will be done prior to taking any study medication. If you are found to be pregnant, 
you will not be randomized and your participation in this study will end. 
 
Once consented, you will be randomized (like the flip of a coin) to receive a loading dose of 
Ticagrelor, which is 180mg, and either a 2 hour infusion of Cangrelor or placebo. Laboratory 
assessments will be performed to measure how your body is responding to the two medications. 
There will be 7 blood draws that will occur at baseline, at the start of infusion, 30 min after start 
of infusion, 1 hour after start, 2 hours after start, 3 hours after start, and 4 hours after start.  
 
You will then enter a washout phase for 1-4 weeks. This will allow time for all of the medication 
to leave your system. After that period is complete, you will return to receive another loading 
dose of Ticagrelor and then based on if you received the Cangrelor or placebo in your first 
infusion, you will switch over to the opposite group. The same laboratory assessments will be 
completed at the same time points. 
 


IRB APPROVED 
Dec 10, 2020 
 
 
4 
After these two visits your participation in the study will be complete.  
 
Most of your blood samples will be processed immediately. However, others will need to be 
stored and processed after the end of the study. Only laboratory staff will have access to these 
samples and your identity will be protected.  
 
WHAT ARE THE POSSIBLE DISCOMFORTS AND RISKS? 
Your study doctor will be responsible for reviewing and monitoring your well-being. 
 
The following are potential risks: 
i. 
Blood drawing. There is the discomfort of blood drawing and you may experience 
bruising, and/or bleeding where the needle is inserted.  Occasionally some people become 
dizzy or feel faint. 
ii. 
The most common side effects of Cangrelor are: bleeding, dyspnea (shortness of breath), 
worsening renal (kidney) function and hypersensitivity. 
iii. 
The most common side effects of Ticagrelor are bleeding, shortness of breath, headache, 
cough, dizziness, and nausea. 
iv. 
It is unknown whether using Cangrelor and Ticagrelor together will increase these risks. 
 
If you are a woman: 
- 
You cannot take part in this study if you are pregnant or breastfeeding a child 
- 
You must agree not to become pregnant while you are in this study 
- 
If you are heterosexually active and able to get pregnant you must use birth 
control during the study. The type of birth control you use must be discussed with 
the study doctor before you begin the study. The study doctor must approve the 
method you use before you can enter the study 
- 
If you get pregnant during the study, you must tell the study doctor immediately. 
You will have to stop taking the study drug. The study doctor will advise you 
about your medical care and will ask you to allow him/her to collect information 
about your pregnancy, your delivery and the health of your baby. There may be 
risks to a fetus or breastfeeding child that are currently not known. 
 
If you are a man: 
- 
If your partner becomes pregnant in the time between when you start taking the 
study drug until your last dose of study drug, you must tell the study doctor 
immediately. The sponsor may ask you and your partner to allow them to collect 
information about her pregnancy, delivery, and the health of the baby 
 
i. 
Loss of confidentiality. 
 
To protect you from above concerns: 
i. 
The blood tests will be drawn by experienced personnel. 
ii. 
Patients who are known to have bleeding problems will not participate in this study to 
reduce this risk. 
iii. 
The data will be stored as secured coded access. 
 
This study may include risks that are unknown at this time. 
 


IRB APPROVED 
Dec 10, 2020 
 
 
5 
Taking part in more than one research study or project may further increase the risks to you. If 
you are currently enrolled or have recently taken part in another research study, you must tell the 
person reviewing this consent form with you. 
 
Throughout the study, the researchers will notify you of new information that may become 
available and might affect your decision to remain in the study. 
 
If you wish to discuss the information above or any discomforts you may experience, you may 
ask questions now or call the Principal Investigator or contact person listed on the front page of 
this form. 
 
WHAT ARE THE POSSIBLE BENEFITS TO YOU? 
There is no guarantee that you will personally benefit by participating in this research study. 
 
HOW COULD OTHERS POSSIBLY BENEFIT FROM THIS RESEARCH STUDY? 
Your participation in this study may help the investigators to learn more about the effects of 
administering Cangrelor after the patient has already been given with Ticagrelor, and may help 
other people in the future. 
 
HOW COULD THE RESEARCHERS BENEFIT FROM THIS RESEARCH STUDY? 
The sponsor is paying the University of Florida for conducting this research study. In general, 
presenting research results helps the career of a scientist. Therefore, the study doctor may benefit 
if the results of this study are presented at scientific meetings or in scientific journals. 
 
CONFLICT OF INTEREST 
Dr. Franchi is a paid consultant for AstraZeneca pharmaceutical the maker of Ticagrelor, which 
is used in the study. Please feel free to ask any questions you may have about this matter. 
 
IF YOU CHOOSE TO TAKE PART IN THIS STUDY, WILL IT COST YOU 
ANYTHING? 
Ticagrelor and either Cangrelor or placebo and its infusion will be provided at no cost to you 
while you are participating in this study. 
 
The Sponsor will pay for all medical services required as part of your participation in this study 
as described above in the section of the consent form headed by the question “What Will Be 
Done Only Because You Are In This Research Study”. This may include some medical services 
that you would have received if you were not in this study.  If you receive a bill for these 
services, please contact Francesco Franchi, MD at 904-244-2060.  
 
All other medical services provided to you that are note directly required by this study will be 
billed to you or your insurance company in the usual manner.  You will be responsible for paying 
any deductible, co-insurance, or co-payments for those services, and for any non-covered or out-
of-network services.  
 
Some insurance companies may not cover costs associated with research studies.  Please contact 
your insurance company for additional information. 
 


IRB APPROVED 
Dec 10, 2020 
 
 
6 
WILL YOU BE PAID FOR TAKING PART IN THIS RESEARCH STUDY? 
You will be paid $100.00 in Visa debit cards for each completed study visit to help cover time 
and travel. It may take up to 48 hours to process your debit card. If you do not complete all of 
your visits you will be paid for the visits that were completed. 
 
If you are paid more than $75 for taking part in this study, your name and social security number 
will be reported to the appropriate University employees for purposes of making and recording 
the payment as required by law. You are responsible for paying income taxes on any payments 
provided by the study. Payments to nonresident aliens must be processed through the University 
of Florida Payroll and Tax Services department.  If the payments total $600 or more in a calendar 
year, the University must report the amount you received to the Internal Revenue Service (IRS). 
The IRS is not provided with the study name or its purpose. If you have questions about the 
collection 
and 
use 
of 
your 
Social 
Security 
Number, 
please 
visit: 
http://privacy.ufl.edu/SSNPrivacy.html. 
 
Your payment for participation in this research study is handled through the University of 
Florida’s Human Subject Payment (HSP) Program. Your information which will include your 
name, address, date of birth, and SSN (depending on amount of money you are paid) is 
protected.  Access to the (HSP) Program site is limited to certain staff with the assigned security 
role.  You will be randomly assigned a specific identification (ID) number to protect your 
identity. 
 
If you have any problems regarding your payment contact the study team at 904-244-5659. 
 
WHAT IF YOU ARE INJURED BECAUSE OF THE RESEARCH STUDY?  
 
If you feel you have a research-related injury, notify the study doctor who will treat you or will 
refer you for treatment. 
 
If you are injured as a direct result of your participation in this study, only the services that you 
receive from any University of Florida Health Science Center healthcare provider will be 
provided without charge. These healthcare providers include physicians, physician assistants, 
nurse practitioners, dentists or psychologists. Any other expenses, including Shands hospital 
expenses, will be billed to you or your insurance provider. 
 
You will be responsible for any deductible, co-insurance, or co-payments. Some insurance 
companies may not cover costs associated with research studies or research-related injuries. 
Please contact your insurance company for additional information. 
 
The Principal Investigator will determine whether your injury is related to your participation in 
this study. 
 
No additional compensation is routinely offered. 
 
The Principal Investigator and others involved in this study may be University of Florida 
employees. As employees of the University, they are protected under state law, which limits 
financial recovery for negligence. 
 


IRB APPROVED 
Dec 10, 2020 
 
 
7 
Please contact the Principal Investigator Francesco Franchi, MD at (904) 244-2060 weekdays 
between the hours of 8:00 a.m. and 5:00 p.m., after regular business hours, you may call (904) 
244-0411 if you experience an injury or have questions about any discomforts that you 
experience while participating in this study. 
 
WHAT OTHER CHOICES DO YOU HAVE IF YOU DO NOT WANT TO BE IN THIS 
RESEARCH STUDY? 
If you choose not to participate in this study, you will still continue receiving your medical care 
just as you normally do. 
 
DO YOU HAVE TO BE IN THIS STUDY? 
Your participation in this study is voluntary. You may decide not to participate or you may leave 
the study at any time. Your decision will not result in any penalty or loss of benefits to which 
you are otherwise entitled. 
 
If you leave this study for any reason, please contact Francesco Franchi, MD or 904-244-2060 
(24 hours).  They will tell you how to stop your participation safely. 
 
CAN YOU BE WITHDRAWN FROM THIS RESEARCH STUDY? 
The FDA, your study doctor, your local institution, has the right to stop your participation in the 
study, or cancel the study, without your consent at any time. Your study doctor may take you off 
the study at any time for any of the following reasons: 
• if he/she decides it is in your best interest. 
• if you do not consent to continue in the study after being told of changes in the research 
that may affect you; 
• or for any reason. 
 


IRB APPROVED 
Dec 10, 2020 
 
 
8 
AUTHORIZATION TO USE AND DISCLOSE INFORMATION FOR RESEARCH 
PURPOSES 
If you agree to participate in this study, the study doctor will create, collect, and use private 
information about you and your health. This information is called protected health information or 
PHI. In order to do this, the study doctor needs your authorization. The following section 
describes what PHI will be collected, used and shared, how it will be collected, used, and shared, 
who will collect, use or share it, who will have access to it, how it will be secured, and what your 
rights are to revoke this authorization. 
 
Your protected health information may be collected, used, and shared with others to determine if 
you can participate in the study, and then as part of your participation in the study. This 
information can be gathered from you or your past, current or future health records, from 
procedures such as physical examinations, x-rays, blood or urine tests or from other procedures or 
tests. This information will be created by receiving study treatments or participating in study 
procedures, or from your study visits and telephone calls.  More specifically, the following 
information may be collected, used, and shared with others: 
 
• Complete past medical history to determine eligibility criteria 
• Records of physical exams 
• Laboratory, x-ray, MRI, and other test results 
• Records about study medications or drugs 
 
This information will be stored in locked filing cabinets or in computers with security passwords. 
 
Some of the information collected could be included in a "limited data set" to be used for other 
research purposes.  If so, the limited data set will include only information that does not directly 
identify you. For example, the limited data set cannot include your name, address, telephone 
number, social security number, or any other photographs, numbers, codes, or so forth that link 
you to the information in the limited data set.  If limited data sets are created and used, 
agreements between the parties creating and receiving the limited data set are required in order to 
protect your identity and confidentiality and privacy. 
 
Your PHI may be collected, used, and shared with others to make sure you can participate in the 
research, throughout your participation in the research, and to evaluate the results of the research 
study.  More specifically, your PHI may be collected, used, and shared with others for the 
following study-related purpose(s): 
 
• to determine the safety of administering Cangrelor after a patient has been pre-treated with 
Ticagrelor 
 
Once this information is collected, it becomes part of the research record for this study. 
 
Only certain people have the legal right to collect, use and share your research records, and they 
will protect the privacy and security of these records to the extent the law allows. These people 
include: 
 
• the study doctor, and research staff associated with this project 
• other professionals at the University of Florida or Shands Hospital that provide study-
related treatment or procedures 
• The University of Florida Institutional Review Board 


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Your PHI may be shared with: 
 
• the study sponsor  
• United States and foreign governmental agencies who are responsible for overseeing 
research, such as the Food and Drug Administration, the Department of Health and Human 
Services, and the Office of Human Research Protections 
• Government agencies who are responsible for overseeing public health concerns such as 
the Centers for Disease Control and federal, state and local health departments 
• WCG IRB 
• Your insurance company for purposes of obtaining payment 
 
Otherwise, your research records will not be released without your permission unless required by 
law or a court order. It is possible that once this information is shared with authorized persons, it 
could be shared by the persons or agencies who receive it and it would no longer be protected by 
the federal medical privacy law. 
 
Your PHI will be used and shared with others until the end of study. 
 
This information will be destroyed 2 years after research is conducted or longer per University of 
Florida and/or FDA requirements. 
 
You may not be allowed to see or copy certain information in your medical records collected in 
connection with your participation with this study while the research is in progress if the research 
includes treatment. When the research study is completed you will have access to inspect or copy 
your records with certain exceptions under applicable law. 
 
You are not required to sign this consent and authorization or allow researchers to collect, use 
and share your PHI. Your refusal to sign will not affect your treatment, payment, enrollment, or 
eligibility for any benefits outside this research study. However, you cannot participate in this 
research unless you allow the collection, use and sharing of your protected health information by 
signing this consent and authorization. 
 
You have the right to review and copy your protected health information. However, we can make 
this available only after the study is finished. 
 
You can revoke your authorization at any time before, during, or after your participation in this 
study.  If you revoke it, no new information will be collected about you. However, information 
that was already collected may still be used and shared with others if the researchers have relied 
on it to complete the research. You can revoke your authorization by giving a written request 
with your signature on it to the study doctor. 
 
Your withdrawal must be made in writing and sent to Francesco Franchi, MD 655 West 8th 
Street, Jacksonville, Florida 32209. 
 
NEW INFORMATION ON THE STUDY DRUG 
You will be informed about any new information, such as adverse reactions (side effects) that 
could affect your decision to continue in this study. You may be asked to sign a new consent 
form if that should occur. 
 


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WHAT IF I BECOME PREGNANT DURING THE STUDY? 
If you are pregnant or nursing before you enroll in the study, you may not participate in the 
study. 
 
WHERE CAN I FIND INFORMATION ABOUT THE STUDY? 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
WHO WOULD YOU CALL IF YOU HAVE ANY QUESTIONS? 
If you have questions about the study, please ask us before signing this form. If you require 
further general information regarding the research study, if at any time you feel you have had 
a research-related injury or reaction to the study drug, or if you have questions, concerns or 
complaints about the research please contact: 
 
Francesco Franchi, MD at 904-244-2060 or 904-244-0411 (24 hours). 
 
If you have questions about your rights as a research subject or if you have questions, concerns or 
complaints about the research, you may contact: 
 
WCG IRB 
1019 39th Avenue SE Suite 120 
Puyallup, Washington  98374-2115 
Telephone:  855-818-2289 
E-mail: researchquestions@wcgirb.com 
 
or 
 
The University of Florida in Jacksonville at (904) 244-9478. 
 
WCG IRB is a group of people who perform independent review of research. 
 
WCG IRB will not be able to answer some study-specific questions, such as questions about 
appointment times.  However, you may contact WCG IRB if the research staff cannot be reached 
or if you wish to talk to someone other than the research staff. 
 


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CONSENT TO PARTICIPATE IN THIS RESEARCH STUDY 
I have been informed about this study’s purpose, procedures, possible benefits and risks. I have 
also been told alternatives to being in the study and how my protected health information will be 
collected, used, and shared with others. I have been given the opportunity to ask questions. My 
questions have all been answered satisfactorily. I agree to be in this research study. I have 
received a copy of this form. 
 
By signing this consent form, I have not given up any of my legal rights. 
 
I authorize the release of my medical records for research or regulatory purposes to those agencies 
listed under the Authorization section of this consent form. 
 
 
 
 
Name of Participant (Print) 
Date 
 
 
 
 
Signature of Participant 
 
As an investigator or the investigator’s representative, I have explained to the participant the 
purpose, the procedures, the possible benefits, and the risks of this research study, the alternative 
to being in the study; and how the subject’s protected health information will be collected, used, 
and shared with others: 
 
 
 
 
 
 
Printed name of person conducting informed consent discussion 
Position 
 
 
 
 
 
 
Signature of person conducting informed consent discussion 
Date