Can Escalation Reduce Acute Myocardial Infarction Mortality in Cardiogenic Shock (CERAMICS Study)
Conditions: Cardiogenic Shock, Acute Myocardial Infarction, STEMI - ST Elevation Myocardial Infarction, NSTEMI - Non-ST Segment Elevation MI, STEMI, NSTEMI, Acute Myocardial Infarction of Right Ventricle (Disorder), Acute Myocardial Infarction of Left Ventricle, Acute Myocardial Infarction With ST Elevation
Sponsor: Henry Ford Health System

 
 
 
 
 
Can Escalation  
Reduce  
Acute Myocardial Infarction  
Mortality  
in Cardiogenic Shock 
(CERAMICS Study) 
Version 1.3 
June 21, 2022 
 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
2 
 
STUDY SPONSOR: 
 
 
Henry Ford Health 
2799 W. Grand Blvd. 
Center for Structural Heart Disease - CFP # 439 
Detroit, Michigan 48202 
(313) 916-8708 
NationalCSI@hfhs.org 
 
PRINCIPLE INVESTIGATOR: 
Mir Babar Basir, DO, FACC, FSCAI 
Director, Acute Mechanical Circulatory Support 
Henry Ford Hospital 
2799 W. Grand Blvd. 
K2-Cardiac Catheterization Laboratory 
Detroit, Michigan 48202 
mbasir1@hfhs.org 
 
 
William W. O’Neill, MD, FACC, MSCAI 
Director, Center for Structural Hear Disease 
Henry Ford Health System 
2799 W. Grand Blvd. 
Center for Structural Heart Disease - CFP # 439 
Detroit, Michigan 48202 
woneill1@hfhs.org 
 
STUDY COORDINATOR: 
Michael Hacala 
Coordinator, Cardiogenic Shock Initiative 
Henry Ford Hospital 
2799 W. Grand Blvd. 
Center for Structural Heart Disease - CFP # 439 
Detroit, Michigan 48202 
mhacala1@hfhs.org 
313-916-7253 
 
 
 
 
 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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TABLE OF CONTENTS 
 
 
 
 
 
Page 
 
1. 
Introduction 
 
4 
 
2. 
Site Selection Criteria & IRB Requirements 
 
6 
 
3. 
Research Procedures 
 
8 
 
4. 
Data Collection  
 
8 
 
5. 
Population and Eligibility Criteria 
 
9 
 
6. 
Risks/Benefits/Alternatives 
 
11 
 
7. 
Data Management 
 
11 
 
8. 
Access to Patient Information 
 
12 
 
9. 
Analysis and Publication of Data 
 
12 
 
10. References 
 
14 
 
11. Appendix 1: NSCI Treatment Algorithm 
 
Attachment 
 
12. Appendix 2: Adoption of the NCSI Treatment Algorithm & Joining 
the CERAMICS Study 
 
Attachment 
 
13. Appendix 3: Patient Screening Form (PSF), Patient Exclusion Form 
(PEF), & Case Report Form (CRF) 
 
Attachment 
 
14. Appendix 4: 30 Day Month Follow-up Form 
 
Attachment 
 
15. Appendix 5: 1 Year Follow-up Form 
 
Attachment 
 
 
 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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1. Introduction 
Acute myocardial infarction complicated by cardiogenic shock (AMICS) is a deadly 
condition with an in-hospital survival rate of ~50%1-3. To date, the only therapy proven to benefit 
patients in AMICS has been early revascularization3. Accordingly, American and European 
guidelines confer a class IB indication for early revascularization in the setting of AMICS4. 
Unfortunately, little progress has been made on improving survival with subsequent therapies, 
including intra-aortic balloon pump counter-pulsation (IABP) 5. This lack of progress is 
worrisome as the incidence of AMICS is increasing6-7.  
Mechanical circulatory support (MCS) devices improve hemodynamics in patients with 
AMICS and use of such devices as adjunctive therapy is supported in US guidelines (Class II a/b 
recommendations). It has been hypothesized that robust MCS devices such as extracorporeal 
membrane oxygenation (ECMO) or transvalvular pumps may improve outcomes further. Despite 
being available for many decades, ECMO is infrequently used because of limited availability and 
a high level of expertise needed for use. ECMO has historically been used by surgeons in the 
operating room with few cardiac catheterization laboratories having access to ECMO. 
Transvalvular MCS devices however are available in over 90% of cardiac catheterization 
laboratories in the United States and have been approved by the FDA for use in AMICS. 
Clinicians have variable experiences and expertise with MCS devices. A retrospective analysis 
of 15,259 patients treated with a MCS between 2009 and 2017 revealed a wide variety of 
outcomes associated with the use of MCS in AMICS.  
Within this context the National Cardiogenic Shock Initiative (NCSI) (NCT03677180) 
was conceived and implemented.  The aim of the study was to evaluate outcomes of patients 
treated with MCS using a protocolized approach emphasizing best practices. The best practices 
included (1) to diagnose and treat patients with AMICS as quickly as possible thereby decreasing 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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the duration patients remain in cardiogenic shock and attempt to decrease use and duration of 
vasopressors and inotropes. (2) To rapidly deliver MCS, reversing end organ hypoperfusion and 
preventing the neuro-hormonal cascade associated with cardiogenic shock. (3) Routine use of 
invasive hemodynamic monitoring with pulmonary artery catheters to guide therapy.  
The final results of the NCSI study were presented at the annual SCAI scientific sessions 
in 2021. Between July 2016 and December 2020, a total of 406 patients were enrolled in the 
study across 73 sites. Patients’ average age was 64±12 years, 24% were female and 67% were 
admitted in shock. 85% of patients were on vasopressors or inotropes, 17% had a witnessed out-
of-hospital cardiac arrest, 27% had in-hospital cardiac arrest, and 9% were under active 
cardiopulmonary resuscitation during MCS implantation. 73% of patients presented in SCAI 
stage C/D shock and 27% in stage E. Patients presented with an average blood pressure of 77/50, 
lactate of 4.8 mmol/dL and cardiac power output (CPO) of 0.67W. In accordance with the NCSI 
treatment algorithm, 71% of patients had MCS implanted prior to PCI. Pulmonary artery 
catheters were used in 93% of patients. 82% of patients presented with ST-elevation myocardial 
infarction with a median door to support time of 78 (IQR 54-116) mins and door to balloon time 
of 82 (IQR 57-114) mins. Procedural survival, survival to discharge, survival to 30-days, and 
survival to 1-year were 99%, 79%, 77%, 62% for patients presenting in stage C/D shock and 
98%, 49%, 46%, 32% for patients in stage E shock (p<0.01). When compared to previously 
conducted studies in AMICS early use of MCS guided by invasive hemodynamics was 
associated with improved outcomes. Given the promising results, a randomized control trial is 
being formulated to further validate these results (RECOVIER IV).  
 The NCSI was an initial step in protocolizing care in AMICS. Over the past 5 years, 
further learnings have helped identify additional best practices that may contribute to further 
improving outcomes. Approximately 30-40% of patients with AMICS have concomitant right 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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ventricular failure (RVF), which is associated with worse morality and may therefore benefit 
from consideration of early right ventricular mechanical circulatory support (RV-MCS) devices. 
Vasopressors have been identified as being independently associated with worse outcomes and 
MCS escalation may lead to further improvement in outcomes. While sites participating in the 
NCSI were early adopters of MCS in AMICS, MCS escalation was open ended and dictated by 
variable local practice patterns. This contributed to the overall low rate of MCS escalation which 
occurred in NCSI.  
In the CERAMICS study, we aim to more clearly delineate care of AMICS regarding 
MCS escalation and ICU management. Our goal is to enroll sites with significant experience in 
MCS, all of whom have the capability of MCS escalation and evaluate outcomes on ~120 
patients focusing on MCS escalation decision making and ICU level management.   
 
2. Site Selection Criteria & IRB Requirements 
 
A total of 20 total sites will be accepted into the CERAMICS study with the goal of 
gathering data and outcomes of ~120 patients treated at participating centers. The study is 
expected to collect data for ~2 years. Prior to joining the study, each site must have broad 
adoption of the NCSI treatment algorithm as the standard of care for AMICS among at least 80% 
of the interventional cardiologists who take STEMI call, as confirmed by the site principal 
investigator (PI). 
 
We are requesting a waiver of informed consent for the CERAMICS study. A Waiver of 
Informed consent is appropriate for the registry for multiple reasons: (1) Eligible patients are 
identified retrospectively after discharge from the index hospitalization, thus obtaining informed 
consent is not feasible. (2) Patients included in the CERAMICS registry are being treated with 
commercially available and FDA-approved devices, and all care is being delivered at the discretion 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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of their treating physicians according to standard local practice. (3) Enrolling only patients who 
provide informed consent would introduce substantial selection bias that reduces the validity of 
this research. It is critically important to track consecutive patients to assess outcomes. This is 
important to identify the total sample size treated and to help identify if there were particular 
biases on the use of MCS, escalation of MCS, etc. We will therefore also track outcomes of those 
not treated with MCS (i.e., exclusion form) as well as with patients treated with MCS including 
when care deviates from the study protocol. Clinicians will not be contacted about the care they 
deliver to patients at any time during the study, and the care will be delivered routinely at 
participating hospitals.  
 
Patients presenting with AMICS are critically ill, with  >40% of patients presenting in 
cardiac arrest, patients are frequently sedated, intubated and have cognitive dysfunction. Due to the 
critical nature and extremes of patients with AMICS, we are requesting a full waiver of informed 
consent and HIPAA authorization from the IRB for data collection and submission under the 
guidelines of 45 CFR 46.116(f) and 45 CFR 64.512(i)(2)(ii).  
 
All study data collection is occurring retrospectively at each time-point only using EMR, 
and there will be no contact between study personnel and patients. Patients will be discharged or 
deceased at the time of study entry. 
 
Sites seeking to join CERAMICS will need approval from their internal/local/system IRB, 
or the ability to either directly use WCG IRB or receive approval from their institutional/local/ 
system IRB to defer to WCG IRB as the IRB of record and oversight for the study. For sites 
choosing to defer study oversight to a national IRB, the study will be reviewed by WCG IRB 
(formerly known as “WIRB” - Puyallup, WA), an independent IRB with AAHRPP accreditation 
and ISO 9001 certification for quality management.  

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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All data is being collected via retrospective EMR review only - no patient contact will be 
made, including screening form, case report form (CRF), and the 30-day and 1-year follow-up 
forms. A limited data set of PHI will be collected (patient age, date of admission, date of MCS 
implant/explant, date of discharge/death) for the CRF or exclusion form, but no direct patient 
identifiers (i.e., name, date of birth, SSN, etc.) other than date of death will be collected. Study 
data forms will be submitted only after hospital discharge.  
 
3. Research Procedures 
 
3.1 
Records Screening 
           This registry will be undertaken at sites only after an IRB has given full approval for the final 
protocol, screening and data collection forms, and the approval of the site PI. During participation in 
the study, study sites will regularly screen all acute MI patient records (STEMI and NSTEMI) for 
patients who presented with cardiogenic shock (AMICS) using the screening form.  
 
4. Data Collection 
 
All study data will be collected retrospectively after patient discharge or death at each study 
time point (post-hospital discharge, 30-days, and 1-year), via chart review only, on all patients who 
present with AMICS regardless of survival to hospital discharge. If a patient meets the study 
inclusion criteria on the screening form, then the following data will be collected (see Appendix 3): 
Retrospective Data (from their medical records) 
• Medical history 
• Admission characteristics 
• Procedure dates and times 
• Procedure characteristics 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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• Diagnostic values 
• Post-procedure information 
Survival Data (collected via EMR review only) (see Appendix 4 and Appendix 5) 
• Mortality at 30 days 
• Mortality at 12 months 
 
5. Population and Eligibility Criteria 
Due to the heterogeneous cohort of patients who present with AMICS, we have defined a 
specific subset of patients from whom outcomes are to be collected (based upon our inclusion and 
exclusion criteria). We anticipated collecting data on approximately 120 adult AMICS patients at 
20 hospital sites in the United States. Data collection and entry will occur after a patient has been 
discharged or deceased. The duration of hospital participation in this research study is anticipated 
to be approximately 2 years.  
 
5.1. Inclusion Criteria 
 
AMICS patients who meet the following inclusion criteria, and none of the 
exclusion criteria, will have a case report form (CRF) completed and submitted within 45 
days of hospital discharge: 
1. Diagnosis of acute myocardial infarction (AMI) with ECG and/or biomarker evidence 
of S-T elevation myocardial infarction (STEMI) or non-S-T elevation myocardial 
infarction (NSTEMI). 
2. Cardiogenic shock is defined as the presence of at least two of the following:  
a. Hypotension (systolic blood pressure ≤90 mm Hg, or inotropes/vasopressors to 
maintain systolic blood pressure ≥90 mmHg). 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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b. Evidence of end organ hypoperfusion: elevated serum lactate levels (venous or 
arterial), cool extremities, oliguria/anuria. 
c. Hemodynamic criteria represented by a cardiac index of < 2.2 L/min/m2 or a 
cardiac power output ≤ 0.6 watts. 
3. Patient is supported with a transvalvular MCS as the initial MCS device. 
4. Patient undergoes PCI within 12 hours of hospital presentation. 
 
 
 
5.2. Registry Exclusion Criteria 
 
AMICS patients who meet any of the following study exclusion criteria will have 
a limited set of data collected via a single-page Patient Exclusion Form completed and 
submitted within 45 days of hospital discharge, which includes the reason for exclusion, 
date of index PCI, and assessment of patient survival to hospital discharge: 
1. Evidence of Anoxic Brain Injury 
2. Unwitnessed out of hospital cardiac arrest or any cardiac arrest in which return of 
spontaneous circulation (ROSC) is not achieved within 30 minutes 
3. IABP placed prior to MCS  
4. Septic, anaphylactic, hemorrhagic, and neurologic causes of shock 
5. Non-ischemic causes of shock/hypotension (pulmonary embolism, pneumothorax, 
myocarditis, tamponade, etc.) 
6. Active bleeding for which MCS is contraindicated  
7. Recent major surgery for which MCS is contraindicated 
8. Mechanical complications of AMI (acute ventricular septal defect (VSD) or acute 
papillary muscle rupture) 
9. Known left ventricular thrombus for which MCS is contraindicated 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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10. Mechanical aortic prosthetic valve 
11. Contraindication to intravenous systemic anticoagulation which precludes placement 
of MCS.  
 
 
6. Risks/Benefits of and Alternatives to Patient Participation 
This is not a treatment study. This is a single-arm registry that captures data generated 
during procedures which are considered standard of care using FDA-approved technologies. 
There are no risks other than breach of confidentiality. To mitigate this risk, only a limited set of 
data directly related to the research will be captured, and all data will be stored in a secure 
REDCap database (please see below).  
 
7. Data Management 
 
Data collected from the participating sites will be securely stored and managed at Henry 
Ford Hospital in Detroit, Michigan. Electronic data will be stored and managed in a secure 
REDCap study database hosted through the Henry Ford Health System Department of Public 
Health Sciences in Detroit, Michigan. REDCap (Research Electronic Data Capture) is a secure, 
web-based application designed to support data capture for research studies. A study-specific 
database was created solely for CERAMICS study that includes only the specific data fields that 
pertain to the data points collected on the case report form (CRF) or Patient Exclusion Form 
(PEF) (see Appendix 3).  
For patients who present to affiliated hospitals with AMICS but are excluded from a CRF 
(see section 5.2), a Patient Exclusion Form will be submitted to track the reasons for exclusion 
(see Appendix 3). 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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The CRFs and Patient Exclusion Forms from an individual site will be transmitted to the 
lead site, Henry Ford Hospital, via secure email and accessed only on hospital-approved, 
password-protected computers and stored on a password-protected and encrypted OneDrive 
system by Microsoft. Access to the OneDrive system and the REDCap database will be managed 
at Henry Ford Hospital by the NCSI coordinator and the investigators of the study via hospital-
approved, password-protected computers inside locked offices in Henry Ford Hospital.  
 
8. Access to Patient Information 
 
The following will have access to the de-identified patient medical information, and any 
necessary research contracts and Data Use Agreements will be completed for each participating 
site. 
Henry Ford Hospital – Detroit, Michigan CERAMICS team:  
o Principal Investigators 
o Co-Investigators 
o Study Research Coordinator(s) 
o Research Nurse(s) 
o Research Assistant(s) 
o Data Coordinator(s) 
o Statistician, based at Henry Ford Hospital 
 
9. Analysis and Publication of Data 
 
There will be planned interim analysis of the data for the purpose of presentations, as well 
as a final analysis and submission for publication of all data at the end of the study. 
Demographics, admission characteristics, procedural characteristics, clinical characteristics, 
procedural outcomes, in-hospital outcomes, disposition, 30-day survival and 1-year survival will 

 
CERAMICS Study – Protocol v1.3 – June 21, 2022 
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be analyzed. The primary outcome of the study will be to assess mortality in AMICS at study 
sites with the ability to implant, and if needed, escalate MCS. The CERAMICS study is an 
observational study and as such prone to bias, confounding and thus causality should not be 
inferred. However, research in AMICS is difficult to perform and there is significant 
heterogeneity in care. Thus, even observational data, despite its limitations, can be practice 
changing and valuable to the care of this high-risk cohort.10  
Statistical methods used for analysis will vary, however, continuous variables will be 
described using the mean and standard deviation. Categorical variables will be described are 
frequency and percentage. Student t test will be used for continuous variables. Chi square test or 
Fisher’s exact tests will be used for categorical variables, as appropriate. All statistical tests 
and/or confidence intervals, as appropriate, will be performed using a 2-sided p value = 0.05. 
Univariate and multivariate logistical regression models will be used to assess the effect of 
variables on outcomes. 
 
 

 
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10. References 
 
1. Goldberg, R. J., Makam, R. C. P., Yarzebski, J., McManus, D. D., Lessard, D., & Gore, J. M. (2016). 
Decade-Long Trends (2001–2011) in the Incidence and Hospital Death Rates Associated with the In-
Hospital Development of Cardiogenic Shock after Acute Myocardial Infarction. Circulation: 
Cardiovascular Quality and Outcomes, 9(2), 117-125. 
 
2. Kolte D, Khera S, Aronow WS, Mujib M, Palaniswamy C, Sule S, Jain D, Gotsis W, Ahmed A, Frishman 
WH, Fonarow GC. Trends in incidence, management, and outcomes of cardiogenic shock complicating ST-
elevation myocardial infarction in the United States. J Am Heart Assoc. 2014 Jan 13;3(1):e000590 
 
3. Hochman, J. S., Sleeper, L. A., White, H. D., Dzavik, V., Wong, S. C., Menon, V., & Boland, J. (2001). 
One-year survival following early revascularization for cardiogenic shock. JAMA, 285(2), 190-192. 
 
4. Bainey, K. R., & Armstrong, P. W. (2016). Transatlantic Comparison of ST-Segment Elevation Myocardial 
Infarction Guidelines: Insights From the United States and Europe. Journal of the American College of 
Cardiology, 67(2), 216-229. 
 
5. Thiele H., Zeymer U., Neumann F.J., et al.(2012) Intraaortic balloon support for myocardial infarction with 
cardiogenic shock. N Engl J Med 367:1287–1296 
 
6. Center for Medicare and Medicaid database, MEDPAR FY14 
 
7. Killip, T., & Kimball, J. T. (1967). Treatment of myocardial infarction in a coronary care unit: a two year 
experience with 250 patients. The American journal of cardiology, 20(4), 457-464. 
 
8. Stretch R, Sauer C.M., Yuh D.D., Bonde P.(2014) National trends in the utilization of short-term 
mechanical circulatory support: incidence, outcomes, and cost analysis. J Am Coll Cardiol 64:1407–1415. 
 
9. William O'Neill, Mir Basir, Simon Dixon, Kirit Patel, Theodore Schreiber, Steven Almany. Feasibility of 
Early Mechanical Support During Mechanical Reperfusion of Acute Myocardial Infarct Cardiogenic Shock 
JACC: Cardiovascular Interventions Mar 2017, 10 (6) 624-625 
 
10. Basir MB, Pinto DS, Ziaeian B, Khandelwal A, Cowger J, Suh W, Althouse A. Mechanical circulatory 
support in acute myocardial infarction and cardiogenic shock: Challenges and importance of randomized 
control trials. Catheter Cardiovasc Interv. 2021 Dec 1;98(7):1264-1274. doi: 10.1002/ccd.29593. Epub 
2021 Mar 7. PMID: 33682260; PMCID: PMC8421448.