Clinical trial NCT04668144
Conditions: Coronary Artery Disease Acute Coronary Syndrome
Sponsor: University of Florida
Start date: 2021-02-18; Completion date: 2023-05-11
Enrollment: 359 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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 prasugrel is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. The overarching aim of this investigation is to rule out a drug drug interaction (DDI) when cangrelor and prasugrel are concomitantly administered in patients undergoing coronary stenting.

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 prasugrel 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. There is an unmet need to better elucidate pharmacodynamic profiles associated with the transition from cangrelor to prasugrel therapy. Of note, prasugrel has recently gone off patent and the availability of a generic formulation will favorably impact its use. Pharmacodynamic studies provide some support on the safety of administering prasugrel at the start of cangrelor infusion. However, the available data does not allow to rule out a DDI given that there was no comparator arm in which prasugrel was either given alone or at the end of cangrelor infusion. The methodological approach for this assessment should rely on comprehensive pharmacodynamics investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic 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 cangrelor and prasugrel are concomitantly administered in patients undergoing coronary stenting.

Arms: arm 1: Prasugrel only administered at the start of PCI arm 2: Cangrelor plus prasugrel concomitantly administered at the start of PCI arm 3: Cangrelor administered at the start of PCI plus prasugrel administered at the end of the cangrelor infusion
Interventions: intervention 1: Cangrelor intervention 2: Prasugrel
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 total infusion will last 2 hours. intervention 2: Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg daily maintenance dose started 24 hours after LD administration

Protocol documents:
Prot_SAP_000.pdf: 
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Pharmacodynamic and pharmacokinetic profiles on switching from cangrelor to prasugrel 
in patients with acute coronary syndrome undergoing percutaneous coronary intervention: 
The Switching Antiplatelet -6 (SWAP-6) 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 prasugrel 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. There is an unmet need to better elucidate 
pharmacodynamic profiles associated with the transition from cangrelor to prasugrel therapy. Of 
note, prasugrel has recently gone off patent and the availability of a generic formulation will 
favorably impact its use. Pharmacodynamic studies provide some support on the safety of 
administering prasugrel at the start of cangrelor infusion. However, the available data does not 
allow to rule out a DDI given that there was no comparator arm in which prasugrel was either 
given alone or at the end of cangrelor infusion. The methodological approach for this assessment 
should rely on comprehensive pharmacodynamics investigations aimed to assess levels of P2Y12 
receptor inhibition, pharmacokinetic 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 cangrelor and 
prasugrel are concomitantly administered in patients undergoing coronary stenting. 


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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 DDI 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 whom the newer generation P2Y12 inhibitors (i.e, prasugrel and ticagrelor) are 
recommended over clopidogrel [16,17,18]. 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 
(which exceeds that of the duration of cangrelor infusion) is such that drug is still systemically 
available to bind with the P2Y12 receptor after discontinuation of cangrelor infusion [3,4,8]. 


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Based on these observations, ticagrelor can be administered before, during, or after cangrelor 
infusion [3,4,8]. 
The transition from cangrelor to prasugrel is associated with transient recovery of platelet 
reactivity, in particular within 1 hour after cangrelor discontinuation, which could be explained 
by a DDI similar to that described for clopidogrel [9]. However, it was observed that recovery of 
platelet function was attenuated when prasugrel was administered 30 minutes before stopping the 
cangrelor infusion [9]. Accordingly, it is recommended that prasugrel be administered at the end 
of cangrelor infusion or 30 minutes prior to discontinuation of infusion [3,4,9]. However, 
recently the ExcelsiorLOAD2 (Impact of Extent of Clopidogrel-Induced Platelet Inhibition 
during Elective Stent Implantation on Clinical Event Rate - Advanced Loading Strategies) study 
showed that prasugrel 60 mg LD given at the start of a 2-hour infusion of cangrelor was 
associated with sufficient platelet inhibition post-cangrelor, with only rare cases of high platelet 
reactivity (HPR) [19]. Moreover, there were no differences with levels of platelet reactivity and 
HPR rates compared with those observed with ticagrelor, which was also given at the start of the 
cangrelor infusion. These observations may be attributed to relatively higher concentration and 
longer half-life of prasugrel’s active metabolite compared with that of clopidogrel [20-23]. 
However, ExcelsiorLOAD2 was not powered to test the non-inferiority on PD effects between 
prasugrel and ticagrelor, but only for the comparison of prasugrel versus clopidogrel. Moreover, 
whether similar findings would be observed with longer infusions of cangrelor (e.g., up to 4 
hours) is unknown. Therefore, although the PD results of this study provide some support on the 
safety of administering prasugrel at the start of cangrelor infusion, the trial design does not allow 
to rule out a DDI given that there was no comparator arm in which prasugrel was either given 
alone or at the end of cangrelor infusion [24]. Moreover, pharmacokinetic (PK) assessments, 


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pivotal to help elucidate a DDI, were not performed. Accordingly, recommendations on timing 
of prasugrel administration in cangrelor treated patients remain unchanged.   
 
STUDY RATIONALE 
Guidelines recommend the preferential use of new generation P2Y12 inhibitors, including 
prasugrel, over clopidogrel in high-risk patients with coronary artery disease (CAD) undergoing 
PCI [16-18]. Since high-risk patients undergoing PCI is a setting in which cangrelor is frequently 
used, there is an unmet need to better elucidate PD profiles associated with the transition from 
cangrelor to prasugrel therapy. To date the uptake of the newer oral P2Y12 inhibitors has been 
mostly limited by costs. However, prasugrel has recently gone off patent and the availability of a 
generic formulation will favorably impact its use. Moreover, to date PD studies assessing the 
transition from cangrelor to prasugrel have been conducted in patients with stable coronary 
artery disease, and current recommendations are based on assessments conducted in patients not 
undergoing PCI [9]. Importantly, acute coronary syndrome (ACS) and PCI are both known to 
affect PK and PD profiles of antiplatelet agents. Overall, these observations strongly underscore 
the need to conduct dedicated investigations to rule out a DDI when transitioning from cangrelor 
to prasugrel and to define the optimal approach for transitioning therapy in real-world high-risk 
patients, including ACS patients, undergoing PCI. The methodological approach for this 
assessment should rely on comprehensive PD assessments aimed to assess levels of P2Y12 
receptor inhibition, 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 cangrelor and prasugrel are 
concomitantly administered in high-risk patients undergoing coronary stenting. 
 
REASERCH PLAN 
Study design 
The Switching Antiplatelet Therapy-6 (SWAP-6) study will be a prospective, 
randomized, open label PD and PK study conducted in high-risk patients undergoing PCI. 
Patients presenting with a non-ST-segment elevation ACS (NSTE-ACS), including unstable 
angina (UA) and NSTE-myocardial infarction (NSTEMI), or with stable CAD but deemed at 
high risk undergoing an invasive management strategy as part of their standard of care will be 
screened. 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 prior to undergoing their diagnostic invasive evaluation to 
define coronary anatomy. 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. 
After undergoing invasive diagnostic evaluation of coronary anatomy, patients 
undergoing PCI will be considered eligible for randomization. Using a computer-based 
randomization system, patients will be randomized in a 1:1:1 fashion to one of the following 
treatment arms: a) prasugrel only administered at the start of PCI (group 1); b) cangrelor plus 
prasugrel concomitantly administered at the start of PCI (group 2); c) cangrelor administered at 


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the start of PCI plus prasugrel administered at the end of the cangrelor infusion (group 3). 
Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg 
daily maintenance dose started 24 hours after LD administration [25]. Cangrelor will be used at 
the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion [26]. 
Study drugs will be administered before passing of the guidewire. The duration of cangrelor 
infusion will be 2 hours or until the end of PCI (whichever is longer). All patients will be on a 
background of aspirin therapy (325 mg loading dose followed by 81 mg daily maintenance 
dose). Patients will be managed according to standard of care. The interventional procedure will 
also be performed according to standard of care with choice of anticoagulant (heparin or 
bivalirudin) at the discretion of the operator. PK and PD assessments will be conducted at 7 time 
points: baseline, 30 minutes after administration of randomized treatment, end of PCI (defined as 
when the guide catheter is removed at procedure completion), 1 hour, 2 hours, 3 hours and 4 
hours after administration of randomized treatment. Figure 1 illustrates the overall study design. 
In patients in which the infusion will be maintained for more than 2 hours (until the end of PCI), 
the 3-hour and 4-hour after time points will be collected 1 hour and 2 hours after stopping 
cangrelor, respectively. 
Although the study will have an open-label design, laboratory personnel will be blinded 
to treatment assignments. During hospital stay, major adverse cardiac events (death, myocardial 
infarction, stroke, and urgent revascularization procedures), serious adverse events (bleeding and 
other adverse events), as well as non-serious adverse events considered to be study related will 
be collected. After completing the study, decisions on medical management, including the choice 
and duration of antiplatelet therapy will be at the discretion of the treating physician.   
 
 


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Figure 1. Overall study design 
 
 
 
 
Study Population 
Inclusion criteria: 
• Patients with NSTE-ACS (UA or NSTEMI) or high-risk patients with stable CAD 
undergoing PCI. NSTE-ACS will be defined as the presence of cardiac ischemic 
symptoms with ischemic changes (but not ST-segment elevation) on electrocardiogram 
with or without a positive troponin. However, normal electrocardiograms will be 
acceptable if the investigator will consider an ACS presentation likely. High-risk CAD 
will be defined at the discretion of the operator performing coronary intervention. 
• Age between 18 and 75 years old 
 
Exclusion criteria:        
• Inability to provide written informed consent 


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• Age >75 years 
• Weight <60 Kg 
• ST-segment elevation myocardial infarction 
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, 
ticagrelor) in past 7 days  
• Known allergies to prasugrel or cangrelor 
• Considered at high risk for bleeding 
• History of ischemic or hemorrhagic stroke or transient ischemic attack 
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, 
apixaban, edoxoban) 
• Planned treatment with glycoprotein IIb/IIIa inhibitors (only bailout use allowed) 
• Fibrinolytics within 24 hours 
• Known platelet count <80x106/mL 
• Known hemoglobin <10 g/dL 
• Active bleeding 
• Known end stage renal disease on hemodialysis 
• Known severe hepatic dysfunction 
• Intubated patients (prior to randomization) 
• 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 the arterial access sheet used for the PCI 
procedure for time points  while patient are in the cath lab (until the end of PCI); post-cath lab 
samples will be drawn through venous sampling. Samples will be collected in anticoagulated and 
serum tubes at each study time point for all PD and PK assessments. The first 2-4 mL of blood 
will be discarded to avoid spontaneous platelet activation. 


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Laboratory assessments will include the following: 
1. VerifyNow PRU assay 
2. VASP-PRI assay 
3. Total Thrombus-Formation Analysis System (T-TAS) 
4. PK 
5. 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 
[27-30]. 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 
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) 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 [31-33]. After a first step of parallel 


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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 
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. 
3) 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) [34]. 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 


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flow rate of 18 μL/min (PL18-AUC10). Low PL18-AUC10 reflect reduced thrombus growth and 
rapid breakdown of the thrombus. 
 
3) Pharmacokinetic (PK) assay: Determination of prasugrel’s active metabolite concentration in 
plasma will be performed using liquid chromatography with tandem mass spectrometry 
according to standard protocols as previously described [27,35]. Blood will be drawn into 
standard EDTA tubes and within 30 seconds a derivatizing agent (3’-methoxyphenacylbromide) 
will be added to capture and stabilize the active metabolite. The geometric mean area under the 
concentration-time curve through the sampling time of the last quantifiable prasugrel’s active 
metabolite concentration (AUC[0-tlast]) will be calculated and the maximum observed plasma 
concentration (Cmax) and time to Cmax (Tmax) of Pras-AM will be recorded. 
4) 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 [36].   
 
Study endpoints, sample size calculation and statistical analysis 
 
The primary end point of the study will be the non-inferiority in PRU measured at 4 
hours of cangrelor plus prasugrel concomitantly administered at the start of PCI versus prasugrel 
only administered at the start of PCI (group 2 vs. group 1). 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 


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deviation of 50 PRU, a sample size of 22 patients per group will allow for the 95% CI to stay 
within ± 45 PRU with a 90% power and alpha=0.05. Considering a 25% data attrition rate due to 
GPI use, hemolysis, drop out or technical problems, 28 patients per group will need to be 
randomized in order to ensure complete available data for analysis. Considering the 3 arms of 
treatment up to 84 patients will need to be randomized. The sample size of this study was 
established according to results of previous PD investigations [28,37]. In line with previously 
reported investigations, 45 PRU was chosen for the noninferiority margin for the upper 95% CI 
limit of the difference [29,30]. Group 3 will be included in study design as this strategy 
represents current standard of care for the transition from cangrelor to prasugrel. However, the 
study will be powered to assess non inferiority of group 2 vs. group 1. Therefore, 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 and PRI>50%, in line with consensus definitions [38].  
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]. One-way analysis of variance or Kruskal-Wallis test will be used to 
compare continuous variables. Chi-squared test will be used to compare categorical variables 
among groups. An analysis of covariance (ANCOVA) method with a general linear model, with 
treatment as the main effect and baseline values of platelet reactivity as a covariate, will be used 
to evaluate the primary end point as well as all between-group comparisons at each time point. 
Least-square mean (LSM) differences in PRU between group 1 and group 2 and the 
corresponding 2-sided 95% CI for the difference will be obtained to assess non-inferiority based 


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on the ANCOVA 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 all the analyses performed. 
Statistical analysis will be performed using SPSS version 22.0 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 prasugrel. 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 1-17): we expect to 
randomize 5 subjects monthly and complete enrollment in 17 months (total: 84 subjects 
randomized). Months 18-20 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). 
 


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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 prasugrel were blurred vision, dizziness, 
headache, nervousness; infrequent events included intracranial hemorrhage (0.79%) and severe 
neutropenia (< 0.1%). The most important adverse effect associated with the use of prasugrel is 
bleeding (2.4%) [39]. However, both cangrelor and prasugrel are standard of care therapies and 
would be potentially utilized as part of standard of care treatment in this study. 
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 [40]. 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 
committee will meet and antiplatelet treatment management will be managed according to 
physician recommendation. 
 
Conflict of Interest 
Dr. Angiolillo (Sub-Investigator) is a consultant for Chiesi, the maker of cangrelor. 
 
 


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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.  


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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. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange 
RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, 
Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of 
Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the 
American College of Cardiology/American Heart Association Task Force on Clinical 
Practice Guidelines. J Am Coll Cardiol. 2016;68:1082-115. 


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18. Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, 
Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, 
Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group ; ESC 
Committee for Practice Guidelines (CPG) ; ESC National Cardiac Societies . 2017 ESC 
focused update on dual antiplatelet therapy in coronary artery disease developed in 
collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary 
artery disease of the European Society of Cardiology (ESC) and of the European 
Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39:213-260. 
19. Hochholzer W, Kleiner P, Younas I, Valina CM, Löffelhardt N, Amann M, Bömicke T, 
Ferenc M, Hauschke D, Trenk D, Neumann FJ, Stratz C. Randomized Comparison of 
Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor: 
The ExcelsiorLOAD2 Trial. JACC Cardiovasc Interv. 2017;10:121-129. 
20. Brandt JT, Payne CD, Wiviott SD, Weerakkody G, Farid NA, Small DS, Jakubowski  JA, 
Naganuma H, Winters KJ. A comparison of prasugrel and clopidogrel loading doses on 
platelet function: magnitude of platelet inhibition is related to active metabolite 
formation. Am Heart J. 2007 Jan;153(1):66.e9-16.  
21. Payne CD, Li YG, Small DS, Ernest CS 2nd, Farid NA, Jakubowski JA, Brandt JT, 
Salazar DE, Winters KJ. Increased active metabolite formation explains the greater 
platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc 
Pharmacol. 2007 Nov;50(5):555-62. 
22. Small DS, Li YG, Ernest CS 2nd, April JH, Farid NA, Payne CD, Winters KJ, Rohatagi 
S, Ni L. Integrated analysis of pharmacokinetic data across multiple clinical 
pharmacology studies of prasugrel, a new thienopyridine antiplatelet agent. J Clin 
Pharmacol. 2011 Mar;51(3):321-32.  
23. Small DS, Farid NA, Payne CD, Konkoy CS, Jakubowski JA, Winters KJ, Salazar DE. 
Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and 
pharmacodynamics of prasugrel. Clin Pharmacokinet. 2010 Dec;49(12):777-98. 
24. Angiolillo DJ, Franchi F. Defining a Role for Prasugrel in Patients With Stable Coronary 
Artery Disease Undergoing Ad Hoc Percutaneous Coronary Intervention. JACC 
Cardiovasc Interv. 2016;9:228-230. 


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25. Prasugrel United States full prescribing information [online], 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022307s002lbl.pdf 
[Accessed August 2018] 
26. Cangrelor United States full prescribing information [online], 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204958lbl.pdf [Accessed 
August 2018] 
27. Rollini F, Franchi F, Hu J, Kureti M, Aggarwal N, Durairaj A, Park Y, Seawell M, Cox-
Alomar P, Zenni MM, Guzman LA, Suryadevara S, Antoun P, Bass TA, Angiolillo DJ. 
Crushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous 
Coronary Intervention: The CRUSH Study. J Am Coll Cardiol. 2016;67:1994-2004. 
28. 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. 
29. 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. 
30. 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, 
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.  
31. Jakubowski JA, Bourguet N, Boulay-Moine D, Sugidachi A, Yamaguchi S, Barragan P, 
Zhou C, Moulard M. Comparison of a new ELISA assay with the flow cytometric assay 
for platelet vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation in 
whole blood to assess P2Y(12) inhibition. Thromb Haemost. 2012;107:388-95. 
32. Barragan P, Paganelli F, Camoin-Jau L, Bourguet N, Boulay-Moine D, Moulard M, 
Bonello L. Validation of a novel ELISA-based VASP whole blood assay to measure 
P2Y12-ADP receptor activity. Thromb Haemost. 2010;104:410-1. 


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33. Abtan J, Silvain J, Kerneis M, O'Connor SA, Barthélémy O, Vignalou JB, Beygui F, 
Brugier D, Collet JP, Montalescot G. Identification of poor response to P2Y12 inhibitors 
in ACS patients with a new ELISA-based vasodilator-associated stimulated 
phosphoprotein (VASP) phosphorylation assay. Thromb Haemost. 2013;110:1055-64. 
34. 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. 
 
35. Farid NA, McIntosh M, Garofolo F, Wong E, Shwajch A, Kennedy M, Young M, Sarkar 
P, Kawabata K, Takahashi M, Pang H. Determination of the active and inactive 
metabolites of prasugrel in human plasma by liquid chromatography/tandem mass 
spectrometry. Rapid Commun Mass Spectrom. 2007;21:169-79. 
36. 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. 
37. Diodati JG, Saucedo JF, French JK, Fung AY, Cardillo TE, Henneges C, Effron MB, 
Fisher HN, Angiolillo DJ. Effect on platelet reactivity from a prasugrel loading dose after 
a clopidogrel loading dose compared with a prasugrel loading dose alone: Transferring 
From Clopidogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary 
Syndrome Patients (TRIPLET): a randomized controlled trial. Circ Cardiovasc Interv. 
2013;6:567-74. 
38. 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 
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. 


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39. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, 
Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson 
CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in 
patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15. 
40. 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 11, 2020 
NCT04668144 
 
 
1 
 
 
University of Florida – Jacksonville 
 
SUBJECT INFORMATION AND CONSENT FORM 
 
TITLE: 
Pharmacodynamic and pharmacokinetic profiles on switching from 
cangrelor to prasugrel in patients with acute coronary syndrome 
undergoing percutaneous coronary intervention: The Switching 
Antiplatelet -6 (SWAP-6) study 
 
PROTOCOL NO.: 
None 
 
IRB Protocol #20203942 
 
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”) 
 
______________________________________________________________________________ 
 
 
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. 


 
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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 the 
blood thinning medications cangrelor and prasugrel are administered together. You will 
be involved in the study for approximately 4 hours.  
b) What is involved with your participation, and what are the procedures to be followed in the 
research? Your involvement will require 7 blood draws (about 2 teaspoons will be drawn 
for each sample) at different time points.  
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. You can receive the study drugs 
without participating in this research.  
f) The information and/or biospecimens collected as part of this research may be de-identified 
for use in future research studies or distributed to another investigator for future research 
studies without additional informed consent. 
g) Your information and/or biospecimens may be used for commercial profit but you will not 
share in the proceeds. 
h) Your biospecimens will not be used to for research involving whole-genome sequencing. 
 
 
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 are having an acute coronary event 
for which you may need a stent in one of your coronary arteries. This is called a percutaneous 
coronary intervention (PCI). For this reason, you also need to be treated with blood thinners. 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 further heart attacks or stroke. 
To prevent a heart attack, there are antiplatelet drugs (blood thinners) to keep your platelets from 
sticking together. Cangrelor (Kengreal) and Prasugrel (Effient) are both antiplatelet drugs used in 
the treatment of patients with coronary artery disease receiving a stent like yours. Cangrelor is 
given through an IV, and is typically given during your heart procedure. Prasugrel is an oral 


 
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medication that patients typically start taking after their procedure has been completed and they 
will continue taking up to a year after, possibly longer.  
 
The purpose of this study is to evaluate if there is any drug to drug interaction when Cangrelor 
and Prasugrel are given at the same time when a patient is receiving a coronary stent.  
 
HOW MANY PEOPLE ARE EXPECTED TO TAKE PART IN THIS RESEARCH 
STUDY? 
Up to 100 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 4 hours after the beginning 
of your stent procedure. Your health status will also be collected for the duration of your hospital 
stay. 
 
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. 
 
You will be consented prior to your heart procedure starting, and you will only be included in the 
study if you end up needing a stent. If so, you will be randomly assigned to 1 of 3 groups. The 
randomization is done on the computer and you will have an equal chance of being in any of the 
3 study groups. The groups are: 
a) Prasugrel only administered at the start of your PCI (group 1) 
b) Cangrelor plus Prasugrel given together at the start of your PCI (group 2) 
c) Cangrelor administered at the start of your PCI plus Prasugrel administered at the end 
of the Cangrelor infusion (group 3). 
 
Randomized treatment of the Cangrelor infusion will be maintained for 2 hours or until the end 
of your stent intervention. Prasugrel will be taken based on your physicians instructions as part 
of your standard of care. Both cangrelor and prasugrel are routinely administered during stent 
procedures as standard of care. The experimental component of this research study is the timing 
of administration and the process of giving the two drugs together. Laboratory assessments to 
measure how your platelets stick together will be drawn at 7 time points. 1) Baseline, 2) 30 
minutes after you receive your randomized treatment 3) at the end of your PCI, 4) at 1 hour, 2 
hours, 3 hours and 4 hours after you receive your randomized treatment.  
 
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 


 
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samples and your identity will be protected.  
 


 
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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 Prasugrel are bleeding, blurred vision, 
dizziness, headache, nervousness. 
IV. 
There may be additional risks of increased bleeding or clotting when Cangrelor 
and Prasugrel are given at the same time. 
V. 
You will also receive aspirin and heparin as part of your standard of care and the 
risks of aspirin or heparin is also increased bleeding. 
 
If you are a woman: 
- 
You cannot take part in this study if you are pregnant or breastfeeding a child 
 
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. 
 
Sometimes during a study, the sponsor may learn new facts about the study drug. It is possible 
that this information might make you change your mind about being in the study. If new 
information is discovered your study doctor will tell you about it right away. 
 
Tell your doctors or dentist that you are in a study and taking a blood thinner. This is very 
important if you have any planned or emergency surgery, dental procedures, or other procedures 
such as a colonoscopy. 
 
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. 
 


 
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WHAT ARE THE POSSIBLE BENEFITS TO YOU? 
Participation in this study may not help to improve your condition. It is also possible that your 
condition may worsen. 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 at the same time as Prasugrel.  
 
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 has no conflicts of interest related to this study. 
 
IF YOU CHOOSE TO TAKE PART IN THIS STUDY, WILL IT COST YOU 
ANYTHING? 
Both cangrelor and prasugrel are routinely administered during stent procedures as standard of 
care.  Therefore, the cost of administering cangrelor and prasugrel will be billed to you or your 
insurance company. You will be responsible for paying any deductible, co-insurance, or co-
payments for those services, and 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. 
 
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. 
 
WILL YOU BE PAID FOR TAKING PART IN THIS RESEARCH STUDY? 
You will not be paid for your participation in this study.  
 
WHAT IF YOU ARE INJURED BECAUSE OF THE RESEARCH STUDY? 
If you are injured as a direct result of your participation in this study please inform the 
investigator and medical treatment will be arranged. 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 


 
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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. 
 
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. You can receive Cangrelor and Prasugrel without participating in this 
research. 
 
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 at 904-244-2060 or 
904-244-0411 (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. 
 
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 


 
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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 if there is a drug to drug interaction when giving Cangrelor at the same time 
as Prasugrel  
 
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 
 
Your PHI may be shared with: 
• the study sponsor  
• United States and foreign governmental agencies who are responsible for overseeing 


 
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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 
• Western Institutional Review Board 
• 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 or as required by law. 
 
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. 
 
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 


 
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site will include a summary of the results. You can search this Web site at any time. 
 


 
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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: 
 
Institutional Review Board (IRB) 
855-818-2289 
researchquestions@wcgirb.com 
 
or 
 
The University of Florida in Jacksonville at (904) 244-9478. 
 
IRB is a group of people who perform independent review of research. 
 
IRB will not be able to answer some study-specific questions, such as questions about 
appointment times.  However, you may contact IRB if the research staff cannot be reached or if 
you wish to talk to someone other than the research staff. 
 
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 
 


 
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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