Clinical trial NCT01950299
Conditions: Acute Myocardial Infarction
Sponsor: Virginia Commonwealth University
Start date: 2014-07-01; Completion date: 2018-12-23
Enrollment: 99 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
VCU-ART3 is a double-blind randomized clinical trial of anakinra high dose vs anakinra standard dose vs placebo in patients with ST-segment elevation myocardial infarction (STEMI) measuring the effects on the acute rise and fall of the plasma C reactive protein levels during the first 14 days.

Detailed description:
VCU-ART3 is a double-blind randomized clinical trial of anakinra high dose vs anakinra standard dose vs placebo in patients with ST-segment elevation myocardial infarction (STEMI) measuring the effects on the acute rise and fall of the plasma C reactive protein levels during the first 14 days

Arms: arm 1: Anakinra 100 mg daily for 14 days arm 2: Anakinra 100 mg twice daily for 14 days arm 3: Placebo for 14 days
Interventions: intervention 1: Anakinra 100 mg intervention 2: Anakinra 100 mg intervention 3: Placebo
Intervention descriptions: intervention 1: Anakinra 100 mg starting immediately and then every 24 hours intervention 2: Anakinra 100 mg starting 12 hours after first dose and then every 24 hours (so that Anakinra is given every 12 hours) intervention 3: Placebo 0.67 ml injections twice daily

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Title: Interleukin-1 Blockade in ST-segment Elevation Acute Myocardial Infarction: The Virginia 
Commonwealth University-Anakinra Remodeling Trial 3 (VCU-ART3) 
 
NCT #: NCT01950299 
 
Document approval date: June 19, 2018 
 
Document Type: Full study protocol and statistical analysis plan 
 
 
 


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
1 
 
 
Interleukin-1 Blockade in ST-segment elevation acute 
myocardial infarction (STEMI) 
 
 
A Randomized Placebo-controlled Double-blinded Study 
 
 
VCU-ART3 study 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator(s): 
Antonio Abbate, MD, PhD; 
 Benjamin W. Van Tassell, PharmD  
 
 
 
Virginia Commonwealth University 
 
 
 
    STUDY PROTOCOL    


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
2 
EDITS TO PRIOR VERSIONS 
1) Changes to Version 08132014 
• 
The personnel list has been updated. 
• 
Section 5.2 – Description of biomarkers tested now updated. 
• 
Section 6.2 – An additional exclusion criterion has been added, “Need for vaccination or 
desensitization that cannot be postponed for 14 days”. 
• 
Section 8.3.1 – We provide a more detailed definition of “related” and “unrelated” to research 
in regards to adverse events. 
• 
Appendix – Case report forms have been added. 
 
2) Changes to Version 04062015 
• 
The personnel list and study sites have been updated to reflect new site at Washington 
Hospital Center. 
• 
Sections 5.2 and 7.6 – The timeframe for ordering the initial echocardiogram and biomarkers 
have been updated. 
• 
Section 6.2 The inclusion criterion “planned or completed coronary angiogram for potential 
intervention” has been updated to reflect the 12 hours timeframe from symptoms, and 
enrollment within 12 hours from angiogram (max 24 hours from symptoms); “desensitization” 
has been clarified to “aspirin desensitization” 
• 
Sections 7.7 and 7.8 – The description of biomarkers assessment has been updated. The 
name of the offsite laboratory has been updated to “True Health Diagnostics”. 
• 
Section 7.8 – Procedures for follow-up beyond one year have been clarified. In-person clinical 
follow up ends at 12 months. 
• 
Section 8.3 – The definition of Adverse Events (AEs) has been revised, and reporting plan 
clarified.  
• 
Appendix C – Screening and enrollment form has been updated to reflect the changes in 
Section 6.2. 
 
3) Changes to Version 11202015 
• 
The personnel list has been updated 
• 
Entry criteria have been updated to remove restrictions related to vaccinations 
 
 


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
3 
TABLE OF CONTENTS 
1) 
Personnel 
2) 
Protocol summary 
3) 
Schematic of study design 
4) 
Background information and significance 
5) 
Objectives 
5.1  
Primary Endpoint(s) 
5.2 
Secondary Endpoints 
6) 
Enrollment in the study 
6.1  
 Screening 
6.2 
 Inclusion & Exclusion criteria 
7) 
Study design 
7.1  
 Treatment with Anakinra 
7.2 
 Allocation concealment 
 
 
7.3  
 Patient Compliance  
7.4 
 Concomitant Medications 
7.5 
 Standard Medical Management 
7.6 
 Echocardiogram 
7.7 
 Biomarkers  
7.8 
 Study Schedule 
7.9    Cost coverage analysis 
 
8) 
Assessment of safety 
8.1  
 Specification of safety parameters 
8.2  
 Data collection and transfer 
8. 3 
Methods of Timing for Assessing, Recording, and Analyzing Safety  
 
 
 
Parameters 
8.4  
 Reporting procedures 
8.5  
 AE/SAE data collection 
8.6  
 The data and safety monitoring (DSMB) plan  
8.7  
 Regulatory reporting 


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
4 
8.8 
 Type and duration of follow up of subjects after adverse events 
8.9  
 Halting rules 
9) 
Adjudication of clinical events 
9.1  
 Event-adjudicating committee 
9.2  
 Definition of the events 
9.3  
 Implications of the findings of the event-adjudicating committee 
10) 
Discontinuation of treatment and withdrawal 
10.1   Reasons for discontinuation of treatment or withdrawal from the study 
10.2   Handling of withdrawals 
10.3   Termination of the study 
11) 
Statistical considerations 
11.1   Study hypothesis 
11.2   Sample size consideration 
11.3   Statistical analysis 
12) 
 Literature cited 
Appendix A: DSMB Chapter for VCU-ART3 
Appendix B: Monitoring Plan 
Appendix C: Case Report Form and Data Collection Forms 
 
 
 
 
 
 
 
 
 
 
 
 


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
5 
 
 
 


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
6 
1)  
PERSONNEL 
 
 
Name  
 
 
 
Role 
 
 
 
Institution/ Division 
Antonio Abbate, MD/PhD 
 
Co-Principal Investigator 
VCU, Cardiology  
Benjamin Van Tassell, PharmD   
Co-Principal Investigator  
VCU, School of Pharmacy  
 
Darryn Appleton, MD  
 
Investigator 
 
   Virginia Cardiovascular Specialists 
Mary Ann Peberdy, MD 
 
Investigator 
 
 
VCU, Cardiology 
Michael Lipinski, MD  
 
Investigator 
Washington Hospital Center, Cardiology 
Ron Waksman, MD 
 
 
Investigator 
Washington Hospital Center, Cardiology 
Salvatore Carbone, MS 
 
Research Assistant 
 
VCU, Cardiology 
Robin Sculthorpe, PharmD 
 
Investigational Pharmacy 
VCU, Pharmacy 
 
Michael C. Kontos, MD 
Event Adjudicating Committee 
VCU, Cardiology  
Keyur Shah, MD 
 
Event Adjudicating Committee 
VCU, Cardiology  
Elizabeth Miller, MD  
Event Adjudicating Committee 
VCU, General Medicine 
 
Dominick Angiolillo, MD 
 
DSMB Chair       
University of Florida, Cardiology 
Richard Cooke, MD 
 
 
DSMB member 
 
VCU, Heart Failure 
Gonzalo Bearman, MD 
 
DMSB member 
 
VCU, Infectious disease 
Ion Jovin, MD  
 
 
DSMB member 
        VCU, Cardiology / McGuire VA 
Jeffrey Kushinka, MD  
 
DSMB member 
 
VCU, General Medicine  
 
Christine DeWilde, RN 
 
DSMB coordinator 
 
VCU, Johnson Center  
 
Charles A. Dinarello, MD 
 
Consultant 
 
 
University of Colorado 
Pierluigi Tricoci, MD  
 
Consultant 
 
 
Duke University 
Filippo Crea, MD 
 
 
Consultant 
 
       Catholic University, Rome, Italy 
Giuseppe Biondi-Zoccai, MD  
Consultant 
 
      Sapienza University, Rome, Italy 
Edward Lesnefsky, MD 
 
Consultant 
 
     VCU, Cardiology / McGuire VA 
George Vetrovec, MD  
 
Consultant 
 
 
VCU, Cardiology 
Juan Lu, PhD  
 
 
Consultant 
 
 
VCU, Biostatistics 
 
Abbreviations: DSMB=Data Safety Monitoring Board 


VCU Clinical Study Protocol 
 
Version 06192018
 
 
 
 
7 
2) 
 PROTOCOL SUMMARY 
 
Title: 
Interleukin-1 Blockade in ST-segment elevation acute myocardial 
infarction (STEMI) 
Population: 
99 patients with STEMI presenting within 12 hours of onset 
Site(s): 
Virginia Commonwealth University, Richmond, VA 
 
Virginia Cardiovascular Specialists, Richmond VA  
 
Washington Hospital Center, Washington DC 
 
Study Duration: 
 
36 months 
Description:   
Phase II clinical trial of Anakinra (standard and higher dose) for 14 
days to quench the acute inflammatory response during STEMI and 
to prevent adverse cardiac remodeling and heart failure after 
STEMI 
 
 
 
 
 
Objectives: 
To determine the effects of IL-1 blockade with Anakinra (standard 
and higher dose) on the area-under-the-curve for C-reactive protein 
(as preferred inflammatory marker in STEMI, and a surrogate for IL-
1 activity), the changes in left ventricular dimensions and function, 
and the clinical outcomes up to 1 year.  
Study Design: 
Multi-center, 
randomized, 
double-blinded, 
placebo-controlled  
clinical trial with allocation to Anakinra 100 mg daily, Anakinra 100 
mg twice daily, or placebo for 14 days. 
 
 
 
 
Estimated Time to  
Complete Enrollment:   
24 months 
 
 
 



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kf Āk_\ Ān`c['kpg\ Ād`Z\ Ān`k_ĀZf ii\ jg f e[ `e^Ā^\ e\ k`ZĀYXZb^if l e[ (ĀCF'+ĀYcf ZbX[ \Ālj `e^Āi\ Zf d Y`eXekĀ
CF'+Āi\Z \ gkf iĀXekX^fe` j k&ĀXeXb`eiX&ĀXd \c`f iXk\[Āk_\Āi\ d f [ \ c`e^ĀgifZ \ j j ĀXe[Āi\ [l Z\ [Ād f ikXc`kp(0
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Zf if eXipĀXik\i pĀj l i^`ZXcĀf ZZclj `f eĀ"3. 
Āmj Ā. /  &ĀJ 6* (*/# &ĀXe[ Āk_\Āj l im`mfi j Ā_X[Ā\m`[ \eZ\Āf] Ād fi \ Ā
]Xmf iXYc\ ĀZXi[ `XZĀi\ d f [ \ c`e^Ā"j d Xcc\i ĀFPĀ\ e[' [`Xjkfc`ZĀXe[Ā\ e[ 'jpjk f c`ZĀ
[ `Xd \ k\ij ĀXe[ Ā_`^_\ iĀFPĀ
\a\Z k`feĀ]iXZk`f e#(0 M`d `cXiĀ\]] \ Zkj Ān\ i\ Āj \\ eĀXcj f Ā`eĀk_\ ĀiXk(ĀN_\ j \ Ā]Xmfi XYc\Ā\ ]]\ ZkjĀf ]ĀCF'+Ā
YcfZ bX[ \ Ān\i \ Āj \ \e ĀXcj f Ālj `e^Ā- ĀX[ [` k`f eXcĀC
F'+ĀYcfZ b\ ij Ān`k_Ā[ `]]\i \ekĀd\Z _Xe`j d j Āf] ĀXZk`f e4ĀC
F'
+NiXgĀn _`Z_Ā`j ĀXĀZ_`d \ i`ZĀgifk\` eĀk_XkĀY`e[j ĀZ`iZl cXk`e^ĀCF'+zĀXe[ĀCF'+{ Āgi\m\ek`e^Ā`kjĀY`e[` e^ĀkfĀ
Figure  2. Kinetics and prognostic value of CRP increase during STEMI. Data from 138 
patients with STEMI show a peak increase in CRP at 72 hours and a significant prognostic 
value of CRP elevation after STEMI. Modified from Roubille et al. Eur J Intern Med 2010. 


VCU Clinical Study Protocol 
 
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11 
the membrane receptor, and 2 anti-IL-1β antibody. All IL-1 blockers had similar effects limiting 
cardiac dilatation and dysfunction without impairing infarct healing.  
Anakinra, recombinant human IL-1 receptor antagonist (Kineret™, Biovitrum, Sweden) is 
approved in USA and Europe for the treatment of rheumatoid arthritis 7, and is also highly effective 
in the treatment of several inflammatory disease, and preliminary studies show benefits also in 
ischemic and hemorrhagic stroke and diabetes. The favorable safety profile of anakinra is 
witnessed by the hundreds of thousands of patients who have been treated in the past decades. 
Anakinra is associated with injection site reactions that are generally mild but occasionally severe. 
Also, anakinra is associated with an increased risk of infections (mainly upper respiratory 
infections) but it is not associated with an increased infection-related mortality showing that the 
infections occurring while on anakinra treatment are generally mild. Moreover, anakinra has been 
also tested in patients with severe sepsis and shock, and while it did not significantly reduce 
sepsis-related mortality, in a meta-analysis of all studies showed a favorable trend toward reduced 
mortality (-18%, P=0.08).  
Based on the preliminary data in the animal AMI model and the established safety profile of 
anakinra, we have conducted 2 separate randomized double blinded pilot studies of anakinra vs 
placebo in patients with STEMI: the first was a pilot study in 10 patients, Virginia Commonwealth 
University Anakinra Remodeling Trial VCU-ART pilot study [clinicaltrials.gov NCT00789724],8 
completed in 2010, followed by a second study in 30 patients, VCU-ART2 pilot study 
[clinicaltrials.gov NCT01175018].9 Both studies included patients with reperfused STEMI who 
were hemodynamically and clinically stable. The 40 patients were followed for 3 months and 
paired cardiac magnetic resonance analyses. Anakinra was used at a standard dose of 100 mg 
daily for 14 days. The primary purpose of these pilot studies was to establish safety and feasibility. 
Mortality and event rates were low in both groups likely reflecting a selection bias toward lower 
risk STEMI due to the fact that patients had to be stable enough to undergo cardiac MRI at 24 
hours: median TIMI STEMI score was indeed 3 (interquartile range 1-4) and only 1 patient died 
(2.5%) within 3 months of STEMI. Overall anakinra showed an acceptable safety profile with only 
2 patients (10%) experiencing adverse event requiring discontinuation of therapy (vs 2 [10%] in 
placebo, P=0.94). Injection site reactions were the most commonly encountered side effect 
occurring in 5 (25%) patients in the anakinra group and 2 (10%) in the placebo group. Nine 
adverse cardiac events (1 death, 2 recurrent MI, 6 new onset heart failure) occurred in 6 placebo 
patients, whereas 3 adverse cardiac events (2 recurrent MI and 1 new onset heart failure) 
occurred in 3 anakinra treated patients (P=0.25). Anakinra-treated patients were significantly less 
likely to experience new onset heart failure (1 patients, 5%) vs placebo-treated patients (6 patient, 
30%, P=0.035, Figure 3).  



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\eki `Zl cXiĀ\ e[' jpj kf c`ZĀmfcld \Ā`e[\o Ā"FP?MP`#ĀXe[Āc\ ]kĀm
\eki `ZlcXiĀ
\a\Z k`feĀ ]iXZk`f eĀ"FP?@#Ā`eĀk_\ Ā\ek`i\Ā Zf _fi kĀn \i \Ā iXk_\i Āj d Xcc(Ā; eXb`eiX'ki\ Xk\[Ā gXk`\e kjĀ
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`eĀgcXZ\Yf 'ki\ Xk\[ ĀgXk`\ ekj Ā"d \ [ `XeĀ[ `]]\ i\e Z\ Ā- (/ Ād c)d , Ā]Xmfi `e^ĀXeXb`eiX&ĀYl kĀef kĀi\XZ_`e^Ā
jkXk`jk`ZXcĀj`^ e`]`ZXeZ\ &ĀJ 7* (+33&Ā@`^l i\ Ā. #(ĀM`d`cXicp&ĀXeXb`eiX'ki\ Xk\[ ĀgXk`\ ekjĀ_X[ ĀXĀd \[` XeĀ%, 
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Anakinra 
Placebo 
P=0.035 
Figure  3. Heart failure-free survival after STEMI. 
Data from the VCU-ART and VCU-ART2 pilot 
studies (N=40) suggest a protective effect of 
anakinra on the incidence of HF after STEMI. 
Heart Failure-free survival 
100 
80 
60 
40 
20 
% 
Weeks after STEMI 
0 
12 
8 
4 
2 
10 
6 
Figure  4. Acute inflammatory response and left ventricular remodeling in STEMI. Data from the VCU-
ART and VCU-ART2 pilot studies (N=40) show blunting of the inflammatory response (C reactive protein 
[CRP] at 72 hours; the dotted line represents the upper normal value of CRP 3 mg/l]. Anakinra also showed 
a trend toward more favorable interval changes in left ventricular end-systolic volume index (LVESVi) and 
LV ejection fraction (LVEF) at 12 weeks. 
Placebo 
Interval change (mL/m2) 
9 
6 
3 
0 
-3 
Anakinra 
P=0.19 
LVESVi 
Placebo 
Anakinra 
P=0.10 
LVEF 
Interval change  (%) 
9 
6 
3 
0 
-3 
Placebo 
Plasma CRP (mg/l) 
30 
20 
10 
Anakinra 
P=0.012 
CRP at 72 hours 
50 
40 
3 



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k_\pĀj `d lckXe\ flj
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Yf k_ĀZf ik`Zfj k\ if `[ j ĀXe[ ĀHM; C>jĀgif df k\ Ā]cl`[ Āi\ k\ ek`f eĀXe[ Ā_pg\i k\ej `f e&Āgfk\ ek`XccpĀ]Xmfi `e^Ā
X[m\i j \ Āi\d f [\c `e^(Ā=fi k`Zf j k\i f`[j ĀXcj fĀ`e[ l Z\ Ā_pg\i ^cpZ\ d `XĀn _`Z_Ād XpĀ]li k_\i ĀZf eki`Ylk\ĀkfĀ
k_\ĀX[m\ ij \Ā\]] \ Zkj (Ā@`eXccpĀZfi k`Zf j k\i f` [j ĀXcj fĀXZk`mXk\ Āk_\ ĀXc[ f j k\i f e\Āi\ Z\ gkfi Ā`eĀk_\Ā_\ Xik&Ā
n _`Z_Ā_Xj ĀY\ \e Āc`eb\ [ Ākf ĀX[ m\ ij \ Āi\ d f[ \ c`e^ĀXe[Ā_\ XikĀ]X`cl i\ &Ān_`c\ĀHM; C>jĀ\ c`d`eXk\ Āk_\ Ā
mXj f [` cXkf ipĀXe[Āj fd \ĀY\ e\ ]`Z`XcĀ\ ]]\Z kjĀf ]Ācf ZXccpĀgif [ l Z\[Ā gifj kX^cXe[` ej ĀXe[ ĀYiX[pb`e`ej (ĀCeĀ
Zf ekiXjk&ĀCF'+ĀYcfZbX[ \ Ā`jĀj \ c\ Zk`m\Ā`eĀ`kjĀ\ ]]\ Zkj4Ā`kĀ[ f \ j Āef kĀ`dg X`iĀf k_\ iĀj `^eXc`e^ĀgXk_nXpj &Ā`kĀ
Figure  5. Anakinra improves aerobic capacity in chronic heart 
failure. Data from a pilot open-label study of anakinra in 7 
patients with chronic systolic heart failure show a significant 
improvement in peak oxygen consumption (VO2) and a reduction 
in C reactive protein (CRP) in all patients at 14 days.  
Peak VO2
(mL/min/kg)
Baseline
14 days
0
5
10
15
20
P=0.016 
Peak VO2 (mL/kg/min) 
Baseline 
14 days 
2 
0 
10 
4 
6 
ays 
8 
5 
Peak VO
10 
2 (mL/kg/m
15 
min)
20 
P=0.016 
P=0.016 
CRP (mg/L) 


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14 
does not have off-target effects, it does not promote fluid retention, hypertension, hyperglycemia 
or any other significant metabolic alterations. No direct effects of anakinra on hemodynamic 
parameters, cardiac function, platelet function or coagulation have been reported in volunteers. 
Therefore, IL-1 blockade is a much safer approach which is documented by the well established 
safety profile of anakinra. 
IL-1 blockers are also substantially different from TNF-α blockers, which have shown 
disappointing results in the treatment of chronic heart failure. Indeed, although the 2 classes are 
occasionally considered interchangeable for the treatment of rheumatic diseases, they should 
not. It is true that elevated IL-1β and TNF-α levels often coexist in acute and chronic illnesses and 
it is also true that TNF-α induces IL-1β synthesis and release, yet the two cytokines have different 
dedicated signaling receptors and different signaling pathways. While IL-1 has a single signaling 
receptor (IL-1R1), TNF-α has 2 membrane receptors (type I and II) with different and opposing 
actions in the heart. The signaling downstream of the receptors is also different for TNF-α and IL-
1 and the pathways are mostly not convergent. This explains the differences in efficacy, safety 
and tolerability of TNF-α and IL-1 blockers in different diseases. In example, patients with adult 
rheumatoid arthritis respond more favorably to TNF-α blockers whereas patients with juvenile 
forms respond more favorably to anakinra. The use of TNF-α blockers is associated with 
increased risk of reactivation of Mycobacterium tubercolosis infection whereas anakinra is not. 
Moreover, as a proof of the differences between the 2 cytokines, patients with TNF-related 
periodic fevers do not respond to IL-1 blockers and patients with cryopyrin-associated periodic 
syndromes (characterized by enhanced IL-1 activity) do not respond to TNF-α blockers. Therefore 
the fact that TNF-α blockers have failed to show a benefit in chronic heart failure does not predict 
whether IL-1 blockers will be effective in AMI, an entirely different clinical condition. In our pilot 
studies in patients with heart failure 10, anakinra significantly reduced IL-6 and CRP levels but had 
no effects on TNF-a levels showing that IL-1 blockade does not provide a reduction in TNF-a. 
Furthermore, anakinra is not immunosuppressive, and actually it has been recently shown to 
prevent stroke-induced immunosuppression.   
In summary, we know that IL-1 activity is enhanced in the heart following ischemia and infarction. 
Experimental animal studies show a central role of IL-1 in infarct healing and promotion of heart 
failure. Pilot clinical trials in patients with STEMI or heart failure also show a favorable safety 
profile and a favorable effect on outcomes. These data represent the basis for hypothesizing 
beneficial effects of IL-1 blockade in patients with STEMI who show signs of enhanced IL-1 activity 
and are at high risk for in-hospital and long-term mortality.  
5) 
OBJECTIVES 
The current research is designed to investigate the safety and efficacy of Anakinra (standard or 
higher dose) in patients with STEMI in a randomized double-blinded trial. We hypothesize that 
anakinra will quench the inflammatory response, improve cardiac remodeling, and reduce the 
incidence of heart failure. 
 


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5.1 
Primary Endpoint 
The primary endpoint of the study is the difference in the area-under-the-curve (AUC) for CRP 
between admission and day 14 between anakinra 100 mg daily and anakinra 100 mg twice daily 
compared with placebo.  
Patients presenting with STEMI have an enhanced IL-1 response as witnessed by elevation in 
serum markers such as CRP.4 We anticipate that patients with STEMI will have increased CRP 
levels and its levels will predict adverse cardiovascular outcomes. We therefore hypothesize that 
anakinra (standard dose) will blunt the CRP increase during STEMI, as seen in the pilot studies, 
and that anakinra (high dose) will further reduce CRP compared with placebo and with anakinra 
(standard dose).  The rationale for measuring AUC for CRP is that it integrates measurements 
across multiple time points to more accurately capture the acute inflammatory response and IL-1 
activity, and is also an established prognostic marker in STEMI. 
 
5.2 
Secondary Exploratory Endpoints 
Additional endpoints will include parameters measured at echocardiography, as well as 
biomarkers, and clinical outcomes. 
Echocardiography: structural and functional echocardiographic parameters include left and right 
ventricular dimensions, mass, systolic and diastolic function. These will provide mechanistic 
insight as to whether the hypothesized changes in the acute inflammatory response will correlate 
with changes in cardiac dimensions or function. The echocardiogram will be ordered acutely 
(within 24 hours) and at 1-year follow up as clinically indicated. 
Biomarkers: Blood will be collected at each time-point throughout the study (admission, 72 hours 
[or discharge whichever comes first], 2 weeks, 3, 6 and 12 months) and analyzed for complete 
blood cell count, metabolic markers (including lipids and lipoproteins, glycemic control and insulin 
resistance, liver and renal panel, sterols), inflammatory markers (i.e. high sensitivity CRP) and 
cardiac biomarkers (i.e. NT-proBNP and troponin I). The data will be collected and electronically 
stored for further analysis at the conclusion of the study. When feasible, results from clinically 
indicated studies will be used. 
Clinical outcomes: Incidence of death (cardiac and non-cardiac), hospitalizations (for HF, for other 
cardiac causes not related to HF, or for non-cardiac reasons) will be recorded at each time-point 
throughout the study (discharge, 2 weeks, 3, 6 and 12 months) in every patient, and then once at 
the end of study, by review of chart and/or telephone interview. The investigators and clinicians 
caring for the patients will remain blinded to treatment allocation and to the CRP data. Adjudication 
of events will be performed by an ad hoc committee blinded to treatment allocation and to CRP 
data. 
 
 
 


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6) 
ENROLLMENT IN THE STUDY  
6.1 
Screening 
Patients will be screened by the investigators at each site in an interval of time between arrival to 
the emergency room and 12 hours after completion of the coronary angiogram and angioplasty, 
with an emphasis toward earlier screening. Those patients who meet entry criteria will be 
approached by the investigators for enrollment. Potential subjects will be provided with an 
Informed Consent Form in accordance with the local Institutional Review Board. Enrolled subjects 
will then undergo complete screening for entry criteria (listed below). Where possible, 
investigators will rely on clinically available laboratory and imaging results; the remaining 
laboratory and imaging analyses will be ordered and billed to the study account. The timely 
treatment of patients with STEMI is facilitated by a system of telepaging that alerts the 
interventional team the need to activate the cardiac catheterization laboratory. The investigators 
involved in this research at each institute will also be alerted so to facilitate timely screening and 
enrollment of the subjects. A waiver to obtain authorization by the subjects to access personal 
health information during screening process will be obtained by the IRB at each center to allow 
for screening. 
 
STEMI represents 1/3 of all AMI and approximately 10% of ED visits for chest pain. We estimate 
approximately 120 STEMI yearly at VCU, >150 STEMI yearly at the Washington Hospital Center, 
and 
>150 
STEMI 
at 
the 
Virginia 
Cardiovascular 
Specialists-affiliated 
hospitals 
(Chippenham/Johnston Willis Medical Center and Henrico Doctors Hospitals) totaling more than 
400 STEMI/year. We propose a conservative enrollment goal of 1 patient/week (total enrollment 
= 99 weeks). Should enrollment fall behind this goal, we will pursue recruitment at the nearby 
University of Virginia (Charlottesville, VA) and other community-based centers in Central or 
Northern Virginia. 
 
 
6.2 
Subject Inclusion and Exclusion Criteria 
In order to be eligible for this study, patients must meet ALL the 3 Inclusion criteria and NONE of 
the Exclusion criteria. 
INCLUSION CRITERIA:  
1) Presentation to the hospital with acute STEMI defined as chest pain (or equivalent) with 
an onset within 12 hours and ECG evidence of ST segment elevation (>1 mm) in 2 or 
more anatomically contiguous leads that is new or presumably new 
 
2) Coronary angiogram for potential intervention completed within 12 hours of symptom 
onset, and enrollment in the study within 12 hours of angiogram (max 24 hours from 
symptom onset) 
 
3) Age>21 (NIH standard) 
 
 


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17 
 
EXCLUSION CRITERIA: 
 
- 
Inability to give informed consent 
- 
Pregnancy or breastfeeding 
- 
Preexisting congestive heart failure (AHA/ACC class C-D, New York Heart Association III-IV) 
- 
Preexisting severe left ventricular dysfunction (EF<20%) 
- 
Preexisting severe valvular heart disease 
- 
Active infections (acute or chronic) 
- 
Recent (<14 days) or active use of immunosuppressive drugs (including but not limited to 
high-dose corticosteroids [>1_mg/kg of prednisone equivalent], TNF-a blockers, cyclosporine) 
not including NSAIDs or corticosteroids used for IV dye allergy only) 
- 
Chronic auto-immune or auto-inflammatory disease (including but not limited to rheumatoid 
arthritis, systemic lupus erythematosus) 
- 
Known active malignancy of any type, or prior diagnosis in the past 10 years 
- 
Anticipated need for cardiac surgery  
- 
Active cancer (or prior diagnosis of cancer within the past 10 years) 
- 
Neutropenia (absolute neutrophil count<1,800/mm3 [or <1,000/mm3 in African-American 
patients]) 
- 
Severe impairment in renal function (estimated glomerular filtration rate <30 ml/kg*min) 
- 
Allergy to rubber or latex 
- 
Allergy to products derived from Escherichia coli 
 
7) 
STUDY DESIGN 
We designed a multi-center, placebo-controlled, double-blinded randomized study of two different 
anakinra regimens (100 mg daily or 100 mg twice daily for 14 days). Patients will be enrolled and 
treated within 12 hours of coronary angiogram/angioplasty and within 24 hours of chest pain 
onset. A baseline echocardiogram will be ordered within the first 24 hours and repeated at 12 
months, as clinically indicated. Biomarkers will be obtained at admission, 72 hours, 14 days, 3, 6 
and 12 months. 
 
 
7.1 
Treatment with Anakinra 
Anakinra and matching placebo syringes have already been provided by the manufacturer, 
Swedish Orphan Biovitrum (SOBI, Stockholm, Sweden) to the Investigational Pharmacy at the 
coordinating center at VCU, where the syringes are stored until ready to be administered to the 
patient. SOBI has also guaranteed a continuous supply of anakinra and placebo should the 
current supply expire prior to completion of the trial. 
Patients will receive the first dose of anakinra 100 mg or placebo within 12 hours of coronary 
angiography/angioplasty. The drug will be administered by the nurse and the patients and will be 
instructed by one of the physicians or pharmacists in the team on how to store and self-administer 
the drug so they can continue at home twice daily for 14 days. The syringes will be labeled 1 
through 28, the patient will be instructed to store them in the fridge and keep them at room 
temperature for few minutes prior to injection subcutaneously. Proper injection technique will be 


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18 
taught. A sharp container sufficient to contain all 14 syringes will be given to the patient to dispose 
the syringes in, and to bring back at the 14-day visit. 
One group of patients will receive anakinra 100 mg twice daily for 14 days, a second group will 
receive anakinra 100 mg alternated with placebo twice daily for 14 days so that anakinra will be 
given every 24 hours, the third group will receive placebo twice daily for 14 days. The patient will 
also be educated on expected side effects and need to inform the investigators about any 
foreseen and unforeseen events.  
 
7.2 
Allocation concealment 
Anakinra or placebo (vehicle) dispensed in small syringes (1 ml) will be provided by the producer 
(Swedish Orphan Biovitrum) for subcutaneous injection twice daily. The syringes for anakinra or 
placebo will be undistinguishable, and labeled with consecutive numbers “1” through “28”. The 
randomization log will be prepared by a consultant outside the institutions involved in the 
enrollment (Giuseppe Biondi-Zoccai, MD, University La Sapienza, Rome, Italy) and sent 
electronically to the director of the Investigational Pharmacy at VCU (Robin Sculthorpe, PharmD). 
Access to randomization log will be restricted and allowed only on an emergency basis, or as 
indicated by the Data Safety and Monitoring Board, or at the end of the study including all data 
collection. 
7.3 
Patient Compliance with Study Intervention 
One goal of the trial is to maximize adherence and retention throughout the study. Adherence will 
be addressed by count of unused syringes at the 14-day study visit.  
 
7.4 
Concomitant Medications 
All concomitant medications will be recorded at each clinic visit. Administration of anakinra with 
medications that affect the immune system (i.e. immunosuppressant) or increase the risk of 
infection (i.e. cancer chemotherapy) is NOT permitted. If a patient requires treatment with such 
medications, he/she will not be eligible for inclusion in the study. If a patient already enrolled in 
the study requires such treatments, the investigational treatment (Anakinra or placebo) will need 
to be discontinued (see reason for discontinuation). 
7.5 
Standard Medical Management 
Patients in the study will receive guideline-based medical treatments as indicated. Such 
treatments may include aspirin, P2Y12 inhibitors, b-adrenergic receptor blockers, angiotensin 
converting enzyme inhibitors or receptor blockers, aldosterone blockers, isosorbide dinitrate, 
hydralazine, digoxin, and statins. 
7.6  
Echocardiogram 
 
The patient will undergo a transthoracic echocardiogram, ordered within the first 24 hours, and 
then again after 12 months, as clinically indicated, to measure left and right ventricular and atrial 
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tricuspidal valve annulus tissue Doppler spectra, ejection time and stroke volume, inferior vena 
cava, aorta and pulmonary artery diameters and Doppler spectra, according to the 
recommendations of the American Society of Echocardiography.[16-18] When feasible, results from 
clinically indicated studies will be used. All images and loops will be acquired in an electronic 
format and transferred to the VCU Pauley Heart Center for blinded centralized measurements at 
the end of the study. 
 
7.7  
Biomarkers assessment 
 
Blood samples will be taken from a peripheral vein at admission, 72 hours, 14 days and 3, 6 and 
12 months. 
 
One EDTA-containing tube, one SST containing tube, one Serum Separator Clot Activator tube 
and one PPT tube will be used for analysis of plasma levels of biomarkers by the True Health 
Diagnostics LLC, Richmond, VA. 
 
One sodium heparin tube will be used to analyze cytokines markers. 
 
 
7.8  
Study Schedule 
 
 
 
 
 
 
 
 
 
Inpatient: 
Admission 
Inpatient: 
72 hours 
Outpatient 
Visit 1:  
14 days 
Outpatient 
Visit 2:  
3 months 
Outpatient 
Visit 3:  
6 months 
Outpatient 
Visit 4:  
12 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening * 
X 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
Clinical assessment ** 
X 
X 
X 
X 
X 
X 
Investigational therapy  
X 
X 
X 
 
 
 
Echocardiogram 
X 
 
 
 
 
X 
CBC 
 
X 
X 
 
 
 
hs-CRP 
X 
X 
X 
X 
X 
X 
Biomarkers 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
*_Pregnancy test will be performed, if indicated 
**_Clinical assessment includes history and physical, medication reconciliation, and assessment 
of adverse events 
 
When feasible, results from clinically indicated studies will be used. 


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Inpatient samples will be taken upon enrollment, at 72 hours (±12 hours [or more if patient 
discharged before 60 hours]).  
Samples will be centrifuged and then refrigerated, and shipped with cold pacs within 24 hours to 
True Health Diagnostics LLC, Richmond, VA. The results will be sent to the PI at VCU and to 
each center by email or fax. 
Outpatient visits will be scheduled at 14 days (±2 days), 3 months (±2 weeks), 6 months (±2 
weeks), and 12 months (±2 weeks). 
 
7.9  
Cost coverage analysis 
 
A cost coverage analysis will be conducted in each center prior to the initiation of the trial to 
determine what constitutes standard of care, which will be billed to the patient or the insurer, and 
what is considered ‘research’ which will be paid for with the study budget.  
 
8)  
ASSESSMENT OF SAFETY 
 
8.1 
Specification of Safety Parameters 
Safety parameters will include data deriving from history and physical examination performed at 
each visit, laboratory data and results of functional and imaging tests. To enhance detection of 
adverse events between visits, all patients will be encouraged to contact the research team at 
any time with concerns or any perceived changes in their healthcare status. 
Disease-related data (MI- and HF-related) will be assessed including changes in symptoms (or 
new symptoms), functional capacity, vital signs (including weight), renal function, or any 
significant changes in medications. 
Data specific to the treatment will also be assessed. The patient will be asked about symptoms 
and examined for signs of infection. Considering that anakinra may mask signs of infection such 
as fever, a low threshold for further investigation will be advocated. A complete cell count will be 
measured at 72 hours and 14 days to exclude the unusual cases of anakinra-related neutropenia 
(ANC<1,000/mm3), for which suspension of active treatment will be encouraged until return to a 
value of ANC>1,800/mm3 (or >1,000/mm3 if patient is African-American). 
Changes to treatment for side-effects or unanticipated problems will be performed without 
breaking the randomization code, unless deemed necessary for the treatment of the individual 
patient by the physician, in which case the physician will be made aware while the remainder of 
the team, especially the investigators performing and interpreting the tests, will be maintained 
blinded.  
 The risks of the tests performed have been described above. In order to reduce risk, the 
procedures will be performed by skilled practitioners in the standard clinical fashion.  
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8.2  
Data collection 
The principal investigator at each site will be provided with a data collection sheets or case report 
forms on which data about the individual subject will be collected. The subjects will be identified 
as a consecutive number in each center (i.e. A01, A02, …A08; B01, B02, … B08; C01 ….). The 
data collected on these forms will not contain any personal identifiable information. The forms will 
be transmitted to the coordinating center at VCU through either a secure HIPAA compliant fax 
line or email correspondence, or hand-delivered. A centralized database of deidentified data will 
be held at VCU. 
8.3 
Methods of Timing for Assessing, Recording, and Analyzing Safety   
 
 
Parameters 
 
8.3.1 Adverse Events 
All Adverse Effects (AEs) will be recorded on an AE form regardless of causality. 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product considered to causally related to the study treatment or 
research conduct. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
medicinal (investigational) product. The occurrence of an AE may come to the attention of study 
personnel during study visits and interviews of a study recipient for medical care, or upon review 
by an investigator or study coordinator. An event that is considered by the investigator(s) to be 
expected and related to the natural history of the disease is NOT considered an AE. 
All events considered AEs including local and systemic reactions not meeting the criteria for 
“serious adverse events” will be reported on the appropriate AE form. Information to be collected 
includes event description, time of onset, clinician’s assessment of severity, relationship to study 
intervention (assessed only by those with the training and authority to make a diagnosis, which 
would include a physician) and time of resolution/stabilization of the event. All AEs occurring while 
on study must be documented appropriately regardless of relationship. All AEs will be followed to 
adequate resolution. 
Any medical condition that is present at the time that the patient is screened should be considered 
as baseline and not reported as an AE. However, if it deteriorates at any time during the study, it 
should be recorded as an AE. 
All AEs must be graded for severity and relationship to study product. 
Severity of Event: All AEs will be assessed by the clinician according to the following guidelines 
to quantify intensity: 
• 
Mild: events require minimal or no treatment and do not interfere with the patient’s daily 
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• 
Moderate: events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning and may 
require systemic drug therapy or other treatment. 
• 
Severe: events interrupt a patient’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually incapacitating. 
• 
Life threatening: any adverse drug experience that places the patient or subject, in the 
view of the investigator, at immediate risk of death from the reaction as it occurred (i.e. 
does not include a reaction that might have caused death had it occurred in a more severe 
form). 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of intensity to be performed. Adverse events characterized as intermittent 
require documentation of onset and duration of each episode.  
Relationship to the intervention: All suspected AEs must have their relationship to study 
intervention assessed using the terms: associated or not associated. In a clinical trial, the study 
intervention must always be a suspect. To help assess, the following guidelines are used to 
assess causality: 
• 
Definitely related: The event is temporally related to the administration of the study 
intervention and, in the opinion of the investigator, no other etiology explains the event. 
• 
Probably related: The event is temporally related to the administration of the study 
intervention and represents, in the opinion of the investigator, the most plausible 
explanation of the event. 
• 
Possibly related: The event is temporally related to the administration of the study 
intervention but, in the opinion of the investigator, it does not represent the most likely 
explanation of the event. 
• 
Definitely Unrelated: The event is temporally independent of study intervention and/or the 
event appears, in the opinion of the investigator, to be explained by another etiology. 
 
8.3.2 Serious Adverse Events 
An SAE is any adverse event/experience occurring between baseline assessments and the 
patients final study visit that results in any of the following outcomes and is considered by the 
investigator(s) to be unexpected or not consistent with the natural history of the disease: 
• 
Death 
• 
Life threatening (subject at immediate risk of death) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in a persistent or significant disability or incapacity 
• 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or surgical intervention to 
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All the unexpected SAE will be promptly (within 24 hours) reported to the local IRB and DSMB 
(see reporting procedures). The DSMB report to the investigators will be forwarded to the NHLBI 
Program Officer, including the discussion of the concerns, and the basis for any recommendations 
that the DSMB has made in response to the concerns (within 7 calendar days if fatal or life-
threatening unexpected, suspected serious adverse reactions; or within 14 days for unanticipated 
problem that is not an SAE or within 15 calendar days for all non-fatal, non-life threatening 
unexpected, suspected serious adverse reactions, or within 30 days of receipt of the DSMB or 
IRB report for all other unanticipated problems or scheduled meetings).   
 
8.4 
Reporting Procedures 
 
8.4.1 Serious Adverse Events 
All unexpected SAEs that result in death or are otherwise reportable SAEs or AEs will be reported 
promptly to the Data Safety Monitoring Board (DSMB) within 1 business day of knowledge of the 
event. 
AEs (serious or nonserious) that transpire secondary to an overdose must also be reported to the 
DSMB within 1 business day of knowledge of the event, using an AE form. 
The SAE form will always be completed as thoroughly as possible with all available details of the 
event, signed by the investigator (or designee), and forwarded to the DSMB within the designated 
time frames. If the investigator does not have all information regarding an SAE, he/she will not 
wait to receive additional information before notifying the DSMB of the event and completing the 
SAE form. The form will be updated when additional information is received.  
The investigator will always provide an assessment of causality at the time of the initial report. 
 
8.5 
AE/SAE Data Collection 
When an AE/SAE is suspected, it is the responsibility of the investigator(s) to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostic reports) relative to the 
event. The investigator will then record all relevant information regarding a suspected AE/SAE on 
the AE form. The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis should be documented 
as the AE/SAE and not the individual signs/symptoms. 
8.6 
The Data and Safety Monitoring Board (DSMB) 
The DSMB is composed of members who are independent from the study operations, in 
compliance with the FDA guidance document (OMB control No. 0910-0581). 
For this study, the DSMB is composed of a coordinator and 5 voting members, including a 
cardiologist from University of Florida in Jacksonville, Florida, a heart failure specialist, a general 
cardiologist, an infectious disease specialist, and a general internal medicine specialist. The 
DSMB will meet every 6 months or sooner in case of unanticipated serious adverse events. The 
DSMB coordinator will provide the board members with data regarding screening, enrollment, 
adverse events and withdrawals, and he/she will not participate in the voting. The board members 


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may request unblinding at any time. Upon request of the DSMB (following positive vote by 3 or 
more members), the coordinator will retrieve the randomization code for one or more individual 
patients (as needed). If necessary the DSMB will inform the investigators of the unblinding of the 
randomization code, if not necessary the investigators (and the patients) will be kept blinded. The 
DSMB may request an expert opinion by one or more non-members, however only the DSMB 
members will vote on any individual issue. The DSMB (following positive vote by 3 or more 
members) may request temporary or permanent halting of the study (see halting rules), or 
interruption of treatment of one or more patients. The minutes from each meeting will be 
distributed to the board members and to the IRB, and not to the investigators unless specifically 
requested by the DSMB. A brief conclusive statement addressing whether the study should 
continue as planned or not will be provided to the investigators and the IRB every 6 months. See 
Appendix – DSMB Chapter. 
8.7  
Regulatory Reporting 
This study is conducted in accordance to the NIH Good Clinical Practice guidelines. An 
Investigational New Drug use (IND # 119067) from the Division of Cardiovascular & Renal 
Products, Center for Drug Evaluation & Research, Food & Drug Administration is held by Dr. 
Abbate. The study protocol, consent, and Data and Safety Monitoring Plan has been approved 
by the VCU IRB. The investigator will notify the Virginia Commonwealth University IRB Panel D, 
the ad hoc Data and Safety Monitoring Board, and the FDA of any severe unexpected adverse 
event. The investigators will provide the NHLBI staff with reports from the DSMB and the IRB in 
a timely fashion (within 7 calendar days if fatal or life-threatening unexpected, suspected serious 
adverse reactions; or within 15 calendar days for all non-fatal, non-life threatening unexpected, 
suspected serious adverse reactions, or within 30 days of receipt of the DSMB or IRB report for 
all other unanticipated problems or scheduled meetings). 
8.8 
Type and Duration of Follow-up of Subjects after Adverse Events 
All AEs and SAEs will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, whichever occurs first. All AEs and SAEs documented at a previous 
visit/contact and designated as ongoing, will be reviewed at subsequent visits/contacts, where 
the designation may remain ongoing. The investigator will ensure that the follow-up includes any 
supplemental investigations as may be indicated to elucidate the nature and/or causality of the 
SAE. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. SAEs that are ongoing at the 
time of the subjects final study visit/contact will be documented as ongoing. 
8.9 
Halting Rules 
The DSMB will monitor the progress of the present trial. No interim efficacy analyses are planned; 
however an interim analysis could be performed at any time to assess efficacy and futility, if 
requested by the 3 or more members of the DSMB. The DSMB will meet regularly to review safety 
data every 6 months (or sooner in case of unanticipated serious adverse events). All meetings 
and actions taken by the committee will be recorded along with the reasons for the actions. These 
documents will include any data summaries or analyses provided to the DSMB and will remain 


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confidential until the study is concluded. The DSMB may choose to stop enrollment on the basis 
of safety data observed. If safety concerns are found, further enrollment will not be allowed until 
issues are resolved. If no safety concerns are found, enrollment will continue until the target 
sample size is reached. 
 
9) 
ADJUDICATION OF CLINICAL EVENTS 
 
9.1 
Event-adjudicating committee 
The event-adjudicating committee is composed of a general cardiologist, a cardiologist with 
training in heart failure, and a general internal medicine specialist. The committee will meet at the 
end of the study and adjudicate all the events. The committee will be blinded to treatment 
allocation. In order to favor allocation concealment, the committee will also be blinded to C-
reactive protein levels, which may be affected by treatment.  
 
9.2  
Definition of the events 
The events adjudicated will include:  
- 
Death;  
- 
Cardiac death (in which a direct cause attributable to cardiac disease is present); 
- 
Sudden cardiac death (in which cardiac death occurred out of the hospital and suddenly; or 
in the hospital due to ventricular arrhythmias unrelated to other concomitant cardiac 
conditions); 
- 
Non-cardiac death (in which the event of death is considered not to be a direct consequence 
of cardiac disease); 
- 
Incidence of heart failure during the index hospitalization (defined as dyspnea beginning or 
persisting >24 hours after admission and meeting both of the following criteria: 
o physical signs of heart failure - including 2 or more of the following: edema, 
crackles/rales, jugular vein distention, hepatojugular reflex, tachypnea, rapid weight 
gain, S3 gallop, abdominal distension/ascites, radiologic evidence of worsening 
edema, pulmonary artery occlusive pressure (wedge) >18 mmHg or cardiac output 
<2.2 l/min-m2; 
o need for additional/increased heart failure therapy - including one of the following:   
initiation or significant increase of oral diuretics, requirement of intravenous diuretics, 
inotropes or vasodilators, need for ultrafiltration due to decompensated heart failure; 
- 
Re-hospitalization for any cause; 
- 
Re-hospitalization for heart failure (meeting all criteria listed above for heart failure during 
index hospitalization) 
- 
Incidence of heart failure (not hospitalized) defined as new or worsening dyspnea and meeting 
one of the two of the following criteria: 
o physical signs of heart failure - including 2 or more of the following: edema, 
crackles/rales, jugular vein distention, hepatojugular reflex, tachypnea, rapid weight 
gain, S3 gallop, abdominal distension/ascites, radiologic evidence of worsening 
edema, pulmonary artery occlusive pressure (wedge) >18 mmHg or cardiac output 
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o need for additional/increased heart failure therapy - including one of the following:   
initiation or significant increase of oral diuretics, requirement of intravenous diuretics, 
inotropes or vasodilators, need for ultrafiltration due to decompensated heart failure; 
- 
Acute myocardial infarction, as defined by the WHO consensus statement 
- 
Unstable angina, or need for coronary revascularization 
- 
Cardiac tachy- or brady-arrhythmias leading to a new hospitalization or to prolongation of 
hospital stay; 
- 
Acute renal failure (defined as in increase in plasma creatinine levels of 50% or 0.5 mg/L); 
- 
Acute respiratory failure (not due to heart failure); 
- 
Sepsis or other serious infection requiring antibiotic therapy; 
- 
Acute stroke. 
The analysis will consider time to first event and time to each event. It will also consider event 
rates at 3, 6 and 12 months, in order to favor comparisons with other studies. The number of days 
free of hospitalization during the first 1, 3, 6 and 12 months will also be measured and compared 
between groups. 
 
9.3 
Implications of the findings of the event-adjudicating committee 
The events will be adjudicated only after the completion of the study, and therefore the findings 
by the committee will have no implications on the conduct of the study. 
 
10)  
DISCONTINUATION OF TREATMENT AND WITHDRAWAL 
 
10.1 
Reasons for Discontinuation of Treatment or Withdrawal from the Study 
Patients may withdraw from the study at any time. The investigators can withdraw any patient at 
any time from the study if medically necessary. It will be extremely important to obtain complete 
follow-up data on each patient, except on those who withdraw consent to release such 
information. It will be documented whether or not each patient completed the study. If for any 
reason the study treatment or observations were discontinued, the reasons will be recorded and 
the IRB will be informed. 
Reasons for discontinuation of anakinra (or placebo): 
1) Neutropenia (ANC<1000/mm3)*; 
2) Systemic infection (sepsis)*; 
3) Surgery *; 
4) Cancer; 
5) Hypersensitivity reaction (rash, anaphylaxis); 
6) Severe injection site reactions *; 
7) Need for immunosuppressant therapy; 
8) Stroke *. 
* treatment may be restarted after condition resolved 
 


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10.2 
Handling of Withdrawals 
Loss to follow-up can occur due to patients’ withdrawal or unreported death. Patients that have 
withdrawn from treatment will still be offered to complete all the functional assessments to analyze 
data in an intention-to-treat strategy. If patients are lost to follow up and their clinical condition 
cannot be established (alive vs dead, hospitalized vs not), they will be excluded from the initial 
analysis, and then reintroduced for sensitivity analysis considering all potential outcomes.  
 
10.3 
Termination of Study 
The decision regarding continuation or termination of the study will be solely based on safety data. 
Interim analyses will be performed upon request by the DSMB. The co-PIs will meet every month 
(or sooner in case of unanticipated serious adverse events) to discuss enrollment, withdrawals, 
and adverse events. If protocol modifications are warranted, close consultation with the DSMB 
and the IRB will be required.  
 
 
11) 
STATISTICAL CONSIDERATIONS 
 
12.1 
Study Hypothesis 
We hypothesize that IL-1 blockade with anakinra will reduce the area-under-the-curve for CRP 
during the first 14 days with a greater reduction to be seen with high-dose anakinra, and that this 
will translate in more favorable cardiac remodeling and prevention of heart failure.  
12.2 
Sample Size Considerations  
The sample size for this study is calculated according to the primary endpoint of difference in the 
AUC for CRP between anakinra (high dose) compared with anakinra (standard dose) and 
placebo. Given an expected average AUC for CRP of 350±250 mg/l for placebo-treated STEMI 
patients (based on the pilot studies) and an average AUC for CRP of 175±150 mg/l for anakinra 
(standard dose)(also based on the pilot studies), 33 patients per group would provide a 85% 
power (alpha 0.025 considering multiple groups) to detect a further 50% reduction in the anakinra 
(high dose)(estimated AUC for CRP of 88±75 mg/l) vs anakinra (standard dose) and a >99% 
power (alpha 0.025) vs placebo. A conservative estimate of 20% loss to follow-up or withdrawal 
would retain >80% power for all analysis.  
 
12.3 
Statistical Analysis 
For statistical analysis, all values will be reported as the median and interquartile range for 
potential deviation from Gaussian distribution. The differences between treatment groups will be 
computed using the Wilcoxon signed-rank test for continuous variables or Fisher’s exact test for 
discrete variables. The differences in interval changes between the treatments will be compared 
using random-effect analysis of variance for repeated measures to analyze the effects of time and 
group allocation. Unadjusted p values will be reported throughout, with statistical significance set 
at the 2-tailed 0.025 level. The analyses will be completed using the Statistical Package for Social 


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Sciences, version 11.0.1, software (SPSS, Chicago, Illinois). Dr. Juan Lu, PhD, an expert in 
biostatistics and clinical trials will oversee all statistical analyses. 
 
 


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13) LITERATURE CITED 
 
1. Velagaleti RS, Pencina MJ, Murabito JM et al. Long-term trends in the incidence of heart 
failure after myocardial infarction. Circulation 2008;118:2057-2062 
2. Eapen ZJ, Tang WH, Felker GM et al. Defining heart failure end points in ST-elevation 
myocardial infarction trials: integrating past experiences to chart a path forward. Circ 
Cardiovasc Qual Outcomes 2012;5:594-600 
3. Mezzaroma E, Toldo S, Farkas D, et al. The inflammasome promotes adverse cardiac 
remodeling following acute myocardial infarction in the mouse. Proc Natl Acadi Scie USA 
2011;108:19725-19730 
4. Roubille F, Samri A, Cornillet L, et al. Routinely-feasible multiple biomarkers score to predict 
prognosis after revascularized STEMI. Eur J Intern Med 2010;21:131-136 
5. Abbate A, Van Tassell BW, Biondi-Zoccai GG. Blocking Interleukin-1 as a novel therapeutic 
strategy for secondary prevention of cardiovascular events. Biodrugs 2012;26:217-233. 
6. Abbate A, Salloum FN, Vecile E, et al. Anakinra, a recombinant human interleukin-1 receptor 
antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 
2008;117:2670-2683 
7. Furst H. Anakinra: review of recombinant human interleukin-l receptor antagonist in the 
treatment of rheumatoid arthritis. Clin Ther. 2004;26:1960-1975 
8. Abbate A, Kontos MC, Grizzard JD, et al. Interleukin-1 blockade with anakinra to prevent 
adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth 
University Anakinra Remodeling Trial [VCU-ART] Pilot Study).  Am J Cardiol 2010;15:1371-
1377 
9. Abbate A, Van Tassell BW, Biondi-Zoccai GG, Kontos MC, Grizzard JD, Spillman DW, Oddi 
C, Roberts CS, Melchior RD, Mueller GH, Abouzaki NA, Rengel LR, Varma A, Gambill ML, 
Falcao RA, Voelkel NF, Dinarello CA, Vetrovec GW. Effects of Interleukin-1 Blockade with 
Anakinra on Adverse Cardiac Remodeling and Heart Failure Following Acute Myocardial 
Infarction (from the VCU-ART2 Pilot Study). Am J Cardiol 2013 – in press. 
10. 
Van Tassell BW, Arena RA, Toldo S, et al. Enhanced interleukin-1 activity contributes to 
exercise intolerance in patients with systolic heart failure. PLoS One 2012;7:e33438 
 
 


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DSMB CHARTER 
Charter, Data and Safety Monitoring Board for  
NHLBI 1R34HL121402-01 
Interleukin-1 blockade in acute myocardial infarction: 
Virgina Commonwealth University Anakinra Remodeling Trial -3  
(VCU-ART3) 
Updated on August 13, 2014 
Executive Secretary: Christine DeWilde, RN – dewildect@vcu.edu 
 
1 
Introduction 
This Charter is for the Data and Safety Monitoring Board (DSMB) for the study: Interleukin-1 
blockade in acute myocardial infarction: Virgina Commonwealth University 
Anakinra Remodeling Trial -3 (VCU-ART3) 
hereafter referred to as “VCU-ART3”. 
The Charter is intended to be a living document.  The DSMB may wish to review it at regular 
intervals to determine whether any changes in procedure are needed.   
2 
Responsibilities of the DSMB  
The DSMB is responsible for safeguarding the interests of study participants, assessing the 
safety and efficacy of study procedures, and for monitoring the overall conduct of VCU-
ART3. 
The DSMB is an independent group advisory to the Director, NHLBI, and is required to provide 
recommendations about starting, continuing, and stopping the study VCU-ART3. In 
addition, the DSMB is asked to make recommendations, as appropriate, to the 
investigators about: 
• 
Participant safety 
• 
Benefit/risk ratio of procedures and participant burden 
• 
Selection, recruitment, and retention of participants 
• 
Adherence to protocol requirements 
• 
Completeness, quality, and analysis of measurements  
• 
Amendments to the study protocol and consent forms 
• 
Performance of individual centers and core labs (as needed) 
• 
Notification of and referral for abnormal findings  
• 
Efficacy of the intervention at study termination (no interim analyses planned) 


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3 
Organization and Interactions 
Communication with DSMB members will be primarily through the executive secretary. It is 
expected that study VCU-ART3 investigators will not communicate with DSMB members 
about the study directly, except when making presentations or responding to questions 
at DSMB meetings or during conference calls.   
a. DSMB Members and NHLBI Program Staff 
DSMB members and their expertise are listed in Appendix A. NHLBI Program Staff involved in 
the study. Consistent with NHLBI policy, the DSMB is assigned an Executive Secretary 
(ES) to provide an unbiased staff interface for the DSMB, especially during executive 
sessions. The ES is responsible for assuring the accuracy and timely transmission of the 
final recommendations and DSMB minutes. 
b.  Scheduling, Timing, and Organization of Meetings 
DSMB meetings will be held at the Virginia Commonwealth University, Richmond, VA, unless 
otherwise specified. For DSMB members residing outside of Virginia, telephone 
participation will be allowed for all meetings. The purpose of the first meeting is to review 
and discuss this Charter, to provide an overview of study VCU-ART3 activities, to review 
and make recommendations about the protocol(s), and to determine the frequency of 
interim analyses and whether data will or will not be masked to identity of randomized 
groups. Enrollment in a study cannot begin until the DSMB’s recommendation for 
approval has been accepted by the Director, NHLBI, and IRB approval has been 
obtained at each site. 
Meetings are usually held approximately twice a year, every 6 months, with additional meetings 
or conference calls scheduled as needed.  Once the DSMB has established its working 
routine, consideration can be given to replacing one meeting per year with a conference 
call, if the agenda permits.  Meetings and conference calls will be scheduled by the DCC 
in collaboration with the NHLBI Program Office.   
• 
For this DSMB, meetings will be held twice per year.  
• 
The DSMB will monitor the progress of the present trial.  
• 
No interim efficacy analyses are planned; however an interim analysis could be 
performed at any time to assess efficacy and futility, if requested by the 3 or more 
members of the DSMB.  
• 
The DSMB may choose to stop enrollment on the basis of safety data observed. If safety 
concerns are found, further enrollment will not be allowed until issues are resolved. If no 
safety concerns are found, enrollment will continue until the target sample size is 
reached. 
 
 
The agenda for DSMB meetings and calls may be drafted by the executive secretary. The 
secretary will finalize the agenda after consultation with the DSMB Chair.  The agenda 


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and meeting materials should be distributed by the DCC 4 weeks before each meeting 
or call.   
The ES will collect and document all potential conflicts of interest from each member of the 
DSMB related to the design, conduct, interpretation, and publication of the study. Before 
each meeting, when the agenda is sent out, the ES will ask all DSMB members to state 
whether they have developed any new conflicts of interest since last meeting.  This 
review will be conducted in addition to the review for conflicts of interest conducted by 
the VCU IRB at the time of initial IRB approval. If a new conflict is reported, the Chair 
and staff will determine if the conflict limits the ability of the DSMB member to participate 
in the discussion. The DSMB also will review adverse event data, other safety data, 
quality and completeness of study data, and enrollment data at each meeting to ensure 
proper trial conduct.   
It is expected that all DSMB members will attend every meeting or call. However, it is 
recognized that this may not always be possible. Quorum for voting is considered to be 
half the number of standing members plus one. The Board may wish to decide if 
particular expertise is needed within the quorum for the meeting to be valid. All standing 
Monitoring Board members are voting members. The Board may also wish to decide in 
advance whether ad hoc members can vote. 
A quorum of this DSMB is considered to be 3 members 
 
c.  Discussion of Confidential Material 
DSMB meetings and calls will be organized into open, closed, and executive sessions. 
• 
During the open sessions, information will be presented to the DSMB by the study 
investigators and NHLBI staff as appropriate, with time for discussion.   
• 
During the closed sessions, the DSMB, DCC, and NHLBI staff will discuss confidential 
data from the study VCU-ART3, including information on efficacy and safety by 
treatment arm, if available.  The DSMB will decide whether to remain masked to the 
treatment assignments at each meeting. If the closed session occurs on a conference 
call, steps will be taken to ensure that only the appropriate participants are on the call, 
and to invite others to re-join the call only at the conclusion of the closed session. 
The DSMB may elect to hold an executive session in which only the DSMB members and 
NHLBI Executive Secretary are present in order to discuss study issues independently.  
Voting on recommendations will follow Roberts’ Rules of Order (Robert's Rules of 
Order Newly Revised (10th Edition) RONR by Henry M. Robert III, William J. Evans 
(Editor), Daniel H. Honemann (Editor), Thomas J. Balch (Editor), Sarah Corbin Robert, 
Henry M. Robert III, General Henry M. Robert) 


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If the executive session occurs on a conference call, steps will be taken to ensure that only the 
appropriate participants are on the call, and to invite others to re-join the call only at the 
conclusion of the executive session. 
At the conclusion of the closed and executive sessions, the participants will be re-convened so 
that the DSMB Chair can provide a summary of the DSMB’s recommendations.  This 
provides an opportunity for study investigators, the DCC, and NHLBI to ask questions to 
clarify the recommendations.  The meeting is then adjourned. 
d. Reports of DSMB Deliberations 
• 
Formal minutes:  The NHLBI ES is responsible for the accuracy and transmission of the 
formal DSMB minutes for the Director, NHLBI, within 14 days of each meeting or call.  
These minutes prepared to summarize the key points of the discussion and debate, 
requests for additional information, response of the investigators to previous 
recommendations, and the recommendations from the current meeting. Prior to 
submission to the Director, minutes will be reviewed by key NHLBI staff before being 
forwarded to the DSMB Chair for final review and approval. The DSMB Chair may sign 
the minutes or indicate approval electronically via email.  Then, the minutes are sent to 
Office of the Director, NHLBI, for OD approval.  Subsequently, recommendations of the 
Board are sent to the DCC and the primary study investigator(s); and included in the 
materials for the subsequent DSMB meeting to be approved by voice vote at that 
meeting. Once they have been voted and approved by the Board, they are considered 
Final. 
• 
Reports to IRBs:  Because this DSMB is convened to supervise a multi-center study, the 
NHLBI program office will prepare a memo documenting Board recommendations and 
submit it to primary study investigator(s) and DCC within 21 days of each meeting. 
Primary study investigator(s) or DCC will forward the memo to each participating 
research site. It is expected that all sites and the DCC will forward the memo to their 
IRB. 
• 
If the DSMB does not identify any safety or other protocol-related concerns, within 30 
days after a DSMB meeting, the NHLBI Program Office will prepare a Summary Report 
that will state that:  
o a review of outcome data, adverse events, and information relating to study 
performance (e.g., data timeliness, completeness, and quality) across all centers 
took place on a given date;  
o the observed frequency of adverse events did not exceed what was expected 
and indicated in the informed consent;  
o a review of recent literature relevant to the research took place and; 
o the DSMB recommended that the study continue without modification of the 
protocol or informed consent. 
 


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• 
If concerns are identified, the report to the clinical centers will outline the concerns, the 
DSMB’s discussion of the concerns, and the basis for any recommendations that the 
DSMB has made in response to the concerns.   
• 
The DSMB report to the investigators will be forwarded to the NHLBI Program Officer, 
including the discussion of the concerns, and the basis for any recommendations that 
the DSMB has made in response to the concerns (within 7 calendar days if fatal or life-
threatening unexpected, suspected serious adverse reactions; or within 14 days for 
unanticipated problem that is not an SAE or within 15 calendar days for all non-fatal, 
non-life threatening unexpected, suspected serious adverse reactions, or within 30 days 
of receipt of the DSMB or IRB report for all other unanticipated problems or scheduled 
meetings).   
• 
The report will be distributed by the DCC to each clinical center.  It is the responsibility of 
each clinical center to forward this information to the local IRB.  
e. Reports to the DSMB  
For each meeting, the DCC, with input from NHLBI staff, will prepare summary reports and 
tables to facilitate the oversight role of the DSMB. The DSMB should discuss at the first 
or subsequent meetings what data they wish to review and how it should be presented.  
f. Statistical Monitoring Guidelines  
At the first meeting, review of the protocol will include review of the statistical analysis plan.  The 
DSMB should discuss the adequacy of that plan. The final plan, whether part of a 
research protocol or separate document, will be maintained as an appendix this charter. 
The DSMB should discuss the statistical monitoring procedures they propose to follow to 
guide their recommendations about termination or continuation of the trial (if applicable). 
These procedures could include guidelines for early termination for benefit, termination 
for futility, and termination for safety reasons (if applicable). 
 
 


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Appendix A: DSMB members 
 
Dominick Angiolillo, MD, PhD 
DSMB Chair 
Dr. Angiolillo is an Associate Professor of Medicine in Cardiology at the University of Florida in 
Jacksonsville. He is board certified in Cardiology and Interventional Cardiology, and serves as 
Medical Director for the Cardiovascular Research Program in the division of Cardiology. 
http://www.hscj.ufl.edu/directory/bio.aspx?id=1318  
 
Richard Cooke, MD  
 
DSMB Member 
 
 
 
Dr. Cooke is an Associate Professor of Medicine in Cardiology at the Virginia Commonwealth 
University, and is the Chief of the Advanced Heart Failure Service in the VCU Pauley Heart 
Center. Dr. Cooke is board-certified in Internal Medicine, Cardiology, Heart Failure, and 
Interventional Cardiology.  http://www.pauleyheart.vcu.edu/staff/cooke.html  
 
Gonzalo Bearman, MD 
 
DSMB Member 
Dr. Bearman is a Professor of Medicine and serves as Chief of the Division of Infectious 
Disease as well as Hospital Epidemiologist. Dr. Bearman is Board Certified in Internal Medicine, 
Infectious Diseases, and General Preventive Medicine and Public Health. 
 
Ion Jovin, MD, PhD  
 
DSMB member 
 
 
Dr. Jovin is an Associate Professor of Medicine in Cardiology, and serves as Director of the 
Cardiac Catheterization Laboratories at the Hunter McGuire Veterans Administration Medical 
Center in Richmond, VA. Dr. Jovin is board certified in Cardiology and Interventional Cardiology. 
http://www.pauleyheart.vcu.edu/staff/jovin.html  
 
Jeffrey Kushinka, MD 
 
DSMB member 
 
 
Dr. Kushinka is an Associate Professor in the Division of General Internal Medicine, has served 
as Interim Chair for 2 years. He is also the clerkship director for 3rd Medical Students and an 
Associate Program Director for the Internal Medicine Residency Program. Dr. Kushinka is board 
certified in Internal Medicine.  
 
 
 


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Appendix B: MONITORING PLAN  
Scope of the plan  
The monitoring plan has the goal to verify that the conduct of the study complies with the 
most updated version of the Research Protocol, and in compliance with the regulation of 
the Institutional Review Board, the Food and Drug Administration, and the guidance of 
dedicated Data and Safety Monitoring Board, and the National Institute of Health.  
 
Responsible parties 
Virginia Commonwealth University, research site: Antonio Abbate, MD 
Washington Hospital Center, research site: Ron Waksman, MD 
Virginia Cardiovascular Specialist, research site: Darryn Appleton, MD 
Virginia Commonwealth University, investigational pharmacy: Robin Sculthorpe, 
RPh 
Coordinating Center Principal Investigator(s): Antonio Abbate, MD; Benjamin Van Tassell, 
PharmD 
FDA IND Principal Investigator: Antonio Abbate, MD, PhD 
NIH Principal Investigator(s): Antonio Abbate, MD, PhD; Benjamin Van Tassell, 
PharmD 
 
The principal investigator (PI) at each local site, as indicated in the submission to the 
Institutional Review Board, is directly responsible for the conduct, oversight, and 
monitoring of study procedures at each site.  
 
The local PI will supervise all study procedures, including the informed consent process, 
enrollment, withdrawal, and all decisions regarding study drug treatment.  
 
The local PI will also be responsible for ensuring the accuracy of the data collected 
through verification with original source data.  
 
Only de-identified data will be collected for the research record. However, the local PI will 
be able to obtain the original source documents if requested by a monitoring or inspecting 


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agency by linking the subject number with the identity of the subject, and retrieving the 
source document using document date, time and author, from the electronic medical 
record (or the existing paper record, if applicable).  
 
All the shipments and handling of the investigational drug will be performed under the 
direct supervision of the Investigational Pharmacy Director at the Virginia Commonwealth 
University, who will be responsible for documentation of received and dispensed drug, 
storage, handling and preparation for patient use. The randomization log is also kept in 
the Investigational Pharmacy and is used for patient allocation. The randomization code 
will be kept secret and released only to the PI upon written request. The local PI may 
request breaking the randomization code if deemed necessary for patient care, see 
Protocol for details. 
 
The handling and dispensing of the investigational drug at each individual site will occur 
under the direct supervision of the local PI, also listed as FDA IND investigator on the 
1572 Form. 
 
Communication between the study investigators and the FDA will occur through the IND 
principal investigator, or, if not available, through one of the IND investigators. 
Investigators other than those listed on the 1572 Form will have no role in handling or 
dispensing the investigational drug, nor will have any role in decision making in this 
regard. 
 
The local investigators and coordinators will respond directly to the local PI. The 
coordinating center PI at the Virginia Commonwealth University will be responsible for 
oversight of individual local PIs.  
 
The local PI is responsible for communication with the coordinating center. Such 
communication will occur either by phone (direct and protected line [804-828-0513]), by 
secure fax (804-828-6765) or by secure email (antonio.abbate@vcuhealth.org OR 
bvantassell@vcu.edu).  


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The local PI is responsible for completing the data collection sheet and also for providing 
a de-identified copy of the source documents (while maintaining ability to access and 
provide de-identified data if necessary) in a timely manner. 
 
The local PI is responsible for complying with the regulations set for reporting of adverse 
events or non-compliance with the research procedure to the local Institutional Review 
Board and at the same time to Coordinating Center PI. 
 
The Coordinating Center PI will be responsible of informing all local PIs, and also for 
complying with the regulations set for reporting of adverse events to the Data and Safety 
Monitoring Board, the FDA, and the NIH. 
 
 
 
 
 
 


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Appendix C: Case Report Forms 
• 
Screening and Enrollment form (1 page) 
• 
Enrollment check list (1 page) 
• 
Enrollment Log (1 page) 
• 
Individual Patient Cover Sheets  (3 pages) 
• 
Individual Visit Assessment Form (4 pages) 
• 
Adverse Event reporting form (1 page) 
 
 
 


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VCU-ART3 
 
 
Enrollment Check List 
VCU-ART3 Subject Number _____ Initials ______Site________Date__________ 
□ Check Inclusion/Exclusion criteria and sign the “Screening and Enrollment Form” 
□ Review Informed Consent Form with Patient and complete all signatures (patient 
and person who conducted informed consent discussion) 
□ Give patient a copy of the signed consent form and Research Team contact card  
□ Give a copy of the consent to secretary to be placed in the patient’s chart 
□ Order Investigational Drug on Cerner 
□ Call Investigational Pharmacy (or ICU Pharmacy if overtime) 
□ Review the “Nurse Protocol” with the Nurse 
□ Fill VCU Lab Sheet Form completing parts highlighted in yellow 
□ Have nurse to collect blood sample and apply Label from “Labs Sheet Form” 
□ Send sample to send to VCU Central Lab (tube station #160) 
□ Witness nurse administer investigational drug 
□ Complete Data Collection Form (Initial Assessment: STEMI presentation, etc...) 
□ Complete Vital Signs Form  
Enrollment Check List verified by (Initials)______________ on ________________ (date) 



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VCU$ART3)Subject)#________)Ini6als)_______)Clinical)Site:)VCU)/)VCS)/)WHC))
Ini$al'Assessment:'STEMI'presenta$on'
Date'_____,)6me)of)symptom)onset)______,))ED)arrival))______,)PCI)6me)_______)
ECG)$)ST)segment)eleva6on)(circle)all)that)apply):)V1)V2)V3)V4)V5)V6)I)II)III)aVF)aVL))'
'
Clinical'condi$ons:)(check)all)that)apply)))
[))])hypotension/shock;)[))])pulmonary)edema;)[))])ventricular)arrhythmias)
[))])persistent)pain;)[)])altered)mental)status)
'
Procedural'data:'check)all)that)apply))'
[))])thrombectomy;)[))])stent)implanta6on,)check)[))])if)at)least)1)is)drug$elu6ng)stent)
[))])bivalirudin;)[))])abciximab/ep6ﬁba6de;)[))])aspirin;)[))])clopidogrel;)[))])prasugrel;))[))])6cagrelor)
'
Past'Medical'History:)(check)all)that)apply)))
[))])Prior)MI;)[))])Prior)PCI;)[))])Prior)CABG;)[))])Heart)Failure;)[))])Prior)CVA;)[))])Hypertension)
[))])Diabetes;)[))])Hyperlipidemia;)[))])Current)Tobacco)user;)[))])Peripheral)Vasc)Disease)
[))])Chronic)Kidney)Disease;)[))])Chronic)Obstruc6ve)Lung)Disease;)[))])Aﬁb;)[))])DVT/PE)
Notes)_______________________________________________________________)
)
STUDY'ITEMS:'(check)all)completed)))
[))])Consen6ng;)[))])Ini6al)Labs)(local/central)lab))on)___/___/___)at)____:____)AM/PM)
[))])Inves6ga6onal)drug)ﬁrst)dose)administered))on)___/___/___)at)____:____)AM/PM)
[))])Medica6on)Reconcilia6on;)[))])Echocardiogram)ordered)(possibly)<24)hrs))
Body)weight:)_____kg/____lb))))))))))))Height:)____m/____c)))))))))))))BMI:)____kg/m2)
Blood)Pressure:)____/____)mmHg)))))HR:)_____min)
[))])72)h)Labs)(±12)hours))(local/central)lab))on)___/___/___)at)____:____)AM/PM)
'
Hospital'outcomes)(check)all)that)apply)))
[))])hypotension/shock,)check)[))])if)requiring)inotropes,)pressors)or)mechanical)support)
[))])pulmonary)edema,)check)[))]))if)requiring)mechanical)ven6la6on)
[))])ventricular)arrhythmias,)check)[))]))if)sustained,)requiring)cardioversion)
[))])acute)renal)failure,)check)[))])if)requiring)renal)replacement)therapy)
[))])re$infarc6on;)[))])repeat)emergent)PCI;)[))])staged)PCI)
Dura6on)of)hospitaliza6on:)_________)days.)
Notes)_______________________________________________________________)
)
DISCHARGE'PLANNING:'(check)all)completed)))
[))])Dispensing)of)inves6ga6onal)drug)(____syringes))by)________)(date)_____,)6me)___))
[))])Pa6ent)educa6on)on)drug)handling,)storage,)and)self$administra6on)(by)________))
[))])Outpa6ent)Hospital)Follow)up)(11$17)days))scheduled)on)________)(loca6on)_____))
[))])Discussed)with)pa6ent)how)to)contact)research)team)24/7)at)804$828$0513)
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VCU$ART3)Subject)#________)Ini6als)_______)Clinical)Site:)VCU)/)VCS)/)WHC))
Follow%up%visit%#1:%14%day%(11417%days)%
Date)of)STEMI_____,)Date)of)F/U)visit)_________)
%
Clinical%condi:ons:)(check)all)that)apply)))
[))])recurrent)angina/myocardial)infarc6on,)check)[))])if)leading)to)re$hospitaliza6on)
[))])heart)failure)symptoms,)_____)NYHA)class)(I!IV),)check)[))])if)re$hospitaliza6on)
[))])re$hospitaliza6on)for)other)cause)(complete)dedicated)sheet))
[))])death,)check)[))])if)presumed)cardiac)death,)check)[))])if)sudden)death)
Notes)_______________________________________________________________)
)
Past%Medical%History:)(changes)vs)prior)–)new)diagnoses)))
[))])___________;)[))])____________;)[))])____________;)[))])__________________)
Notes)_______________________________________________________________)
)
STUDY%ITEMS:%(check)all)completed)))
[))])Assessment)of)compliance))with)inves6ga6onal)drug)performed)by)_________)
)))))(used)syringes)______;)returned)syringes)______))
[))])Send$out)Labs)(HDL);)[))])Medica6on)reconcilia6on;))
[))])Scheduling)F/U)visit)for)_______,)loca6on)_____________)
Body)weight:)_____kg/____lb))))))))))))Height:)____m/____Z)))))))))))))BMI:)____kg/m2)
Blood)Pressure:)____/____)mmHg)))))HR:)_____min)
)
Follow%up%visit%#%2:%3%months%(10414%weeks)%
Date)of)STEMI_____,)Date)of)F/U)visit)_________)
%
Clinical%condi:ons:)(check)all)that)apply)))
[))])recurrent)angina/myocardial)infarc6on,)check)[))])if)leading)to)re$hospitaliza6on)
[))])heart)failure)symptoms,)_____)NYHA)class)(I!IV),)check)[))])if)re$hospitaliza6on)
[))])re$hospitaliza6on)for)other)cause)(complete)dedicated)sheet))
[))])death,)check)[))])if)presumed)cardiac)death,)check)[))])if)sudden)death)
Notes)_______________________________________________________________)
)
Past%Medical%History:)(changes)vs)prior)–)new)diagnoses)))
[))])___________;)[))])____________;)[))])____________;)[))])__________________)
Notes)_______________________________________________________________)
)
STUDY%ITEMS:%(check)all)completed)))
[))])Send$out)Labs)(HDL);)[))])Medica6on)reconcilia6on;)
[))])Scheduling)F/U)visit)for)_____________,)loca6on)_______)
Body)weight:)_____kg/____lb))))))))))))Height:)____m/____Z)))))))))))))BMI:)____kg/m2)
Blood)Pressure:)____/____)mmHg)))))HR:)_____min)
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VCU$ART3)Subject)#________)Ini6als)_______)Clinical)Site:)VCU)/)VCS)/)WHC))
Follow%up%visit%#3:%6%months%(22526%weeks)%
Date)of)STEMI_____,)Date)of)F/U)visit)_________)
%
Clinical%condi=ons:)(check)all)that)apply)))
[))])recurrent)angina/myocardial)infarc6on,)check)[))])if)leading)to)re$hospitaliza6on)
[))])heart)failure)symptoms,)_____)NYHA)class)(I!IV),)check)[))])if)re$hospitaliza6on)
[))])re$hospitaliza6on)for)other)cause)(complete)dedicated)sheet))
[))])death,)check)[))])if)presumed)cardiac)death,)check)[))])if)sudden)death)
Notes)_______________________________________________________________)
)
Past%Medical%History:)(changes)vs)prior)–)new)diagnoses)))
[))])___________;)[))])____________;)[))])____________;)[))])__________________)
Notes)_______________________________________________________________)
)
STUDY%ITEMS:%(check)all)completed)))
[))])Send$out)Labs)(HDL);)[))])Medica6on)reconcilia6on;))
[))])Repeat)echocardiogram)to)be)scheduled)for)12)month)visit)
[))])Follow)up)visit)for)________,)loca6on)________)
Body)weight:)_____kg/____lb))))))))))))Height:)____m/____\)))))))))))))BMI:)____kg/m2)
Blood)Pressure:)____/____)mmHg)))))HR:)_____min)
Follow%up%visit%#4:%12%months%(11513%months)%
Date)of)STEMI_____,)Date)of)F/U)visit)_________)
%
Clinical%condi=ons:)(check)all)that)apply)))
[))])recurrent)angina/myocardial)infarc6on,)check)[))])if)leading)to)re$hospitaliza6on)
[))])heart)failure)symptoms,)_____)NYHA)class)(I!IV),)check)[))])if)re$hospitaliza6on)
[))])re$hospitaliza6on)for)other)cause)(complete)dedicated)sheet))
[))])death,)check)[))])if)presumed)cardiac)death,)check)[))])if)sudden)death)
Notes)_______________________________________________________________)
)
Past%Medical%History:)(changes)vs)prior)–)new)diagnoses)))
[))])___________;)[))])____________;)[))])____________;)[))])__________________)
Notes)_______________________________________________________________)
)
STUDY%ITEMS:%(check)all)completed)))
[))])Send$out)Labs)(HDL);)[))])Medica6on)reconcilia6on;))
[))])Repeat)echocardiogram;))
[))])Scheduling)F/U)visit)with)clinical)provider)
Body)weight:)_____kg/____lb))))))))))))Height:)____m/____\)))))))))))))BMI:)____kg/m2)
Blood)Pressure:)____/____)mmHg)))))HR:)_____min)
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VCU$ART3)Subject)#________)Ini6als)_______)Clinical)Site:)VCU)/)VCS)/)WHC))
Follow%up%visit:%Extra1visit%
Date)of)STEMI_____,)Date)of)F/U)visit)_________)
%
Clinical%condi6ons:)(check)all)that)apply)))
[))])recurrent)angina/myocardial)infarc6on,)check)[))])if)leading)to)re$hospitaliza6on)
[))])heart)failure)symptoms,)_____)NYHA)class)(I!IV),)check)[))])if)re$hospitaliza6on)
[))])re$hospitaliza6on)for)other)cause)(complete)dedicated)sheet))
[))])death,)check)[))])if)presumed)cardiac)death,)check)[))])if)sudden)death)
Notes)_______________________________________________________________)
)
Past%Medical%History:)(changes)vs)prior)–)new)diagnoses)))
[))])___________;)[))])____________;)[))])____________;)[))])__________________)
Notes)_______________________________________________________________)
)
STUDY%ITEMS:%(check)all)completed)))
[))])Send$out)Labs)(HDL);)[))])Medica6on)reconcilia6on;))
[))])Repeat)echocardiogram)to)be)scheduled)for)12)month)visit)
[))])Follow)up)visit)for)________,)loca6on)________)
Body)weight:)_____kg/____lb))))))))))))Height:)____m/____\)))))))))))))BMI:)____kg/m2)
Blood)Pressure:)____/____)mmHg)))))HR:)_____min)
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