A Pilot Study in Feasibility and Safety: Point of Care Testing With Thromboelastography (TEG) for Blood Product Transfusion in Patient's Requiring Extracorporeal Membrane Oxygenation (ECMO)
Phase: NA
Conditions: Heart Disease, Lung Disease
Sponsor: Stephen Esper

 
 
 
 
 
 
 
 
 
 
 
Study Title: A Pilot Study in Feasibility and Safety: Point of Care testing with thromboelastography (TEG) 
for blood product transfusion and coagulation in patient’s requiring extracorporeal membrane oxygenation 
(ECMO) 
Principal Investigator: Stephen Esper, MD, MBA 
 
Document: Study Protocol 
Document Date: 29 AUG 2019 
 
NCT #: NCT02887820 
STUDY #: STUDY19070239 
 
 

Date: Tuesday, December 3, 2024 12:55:43 PM
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View: Pitt SF: Basic Study Information 8.2
Basic Study Information
 
1. * Title of study:
A Pilot Study in Feasibility and Safety of Point of care testing with
thromboelastography (TEG) for blood product transfusion and anticoagulation in
patients requiring Extracorporeal Membrane Oxygenation (ECMO)
2. * Short title:
Evaluate the feasibility of following TEG algorithm in patients requiring ECMO
3. * Brief description:
This is a pilot study that seeks to evaluate the feasibility and safety of using a TEG
algorithm in addition to traditional laboratory tests to guide transfusion and
anticoagulation management of ECMO patients. Patients requiring ECMO exhibit a
high risk of mortality due to bleeding and thrombosis, as the non-biological surface
of the extracorporeal surface activates both procoagulant and anticoagulant
mechanisms (1). Using TEG as a point-of-care device to provide individualized,
goal-directed therapy in this population may help decrease blood product
transfusion and lead to improved blood management overall.
All adult patients requiring ECMO will be considered for the trial, with a target
enrollment of 50 participants over a two-year period. For each enrolled participant, a
TEG transfusion algorithm will be followed for patients exhibiting inadequate
hemostasis in the operating room (Flowchart 1), and then a second TEG algorithm
will be followed in the ICU when hemostasis is normal and heparin is introduced
(Flowchart 2). Statistical analysis of the feasibility and compliance of using a TEG
algorithm will determine the likelihood of exploring future clinical trials involving TEG-
driven coagulation and transfusion management of the ECMO population.
4. * What kind of study is this?
Single-site study
 
5. * Will an external IRB act as the IRB of record for this study?
  Yes  No
6. * Local principal investigator:
Stephen Esper
* Is this your first submission, as PI, to the Pitt IRB?
  Yes  No

7. * Does the local principal investigator have a financial interest related to this
research?
  Yes  No
8. Attach the protocol:
Sponsor/Multicenter/Investigator-initiated protocol
Coordinating Center supplement
Emergency Use Consent/ Protocol/ FDA Form 3926
Exempt Application form
 Document
Category
Date Modified
Document History
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View: Pitt SF: Funding Sources (not integrated with Grants)
Funding Sources
1. * Indicate all sources of support:
External funding
2. * Identify each organization supplying funding for the study:
Funding Source
Sponsor's
Funding ID
Grants
Office ID
AttachmentsPitt
Awardee
Grant
Recipient
American Heart
Association
 
 
AHA Plan
 
 

View: Pitt SF: Study Team Members
Study Team Members
1. * Identify each person involved in the design, conduct, or reporting of the
research:
Name
Roles
Department/SchoolAffiliation
Involved
in
Consent
Qualifications
Financial
Interest
Michael
Boisen
Co-
investigator
U of Pgh | School
of Medicine |
Anesthesiology
Pitt
faculty
yes
Michael Boisen,
MD, Assistant
Professor of
Anesthesiology-
Co-investigator,
The effect of
Antithrombin III
on morbidity
and mortality in
patients und...
no
Jonathan
D'Cunha
Co-
investigator
U of Pgh | School
of Medicine |
Cardiothoracic
Surgery
Pitt
faculty
yes
Jonathan
D’Cunha, MD,
Visiting
Associate
Professor of
Surgery;
Surgical
Director of Lung
Transplantation;
Vice Chairman
Academic
Affairs and
Educatio...
no
Melanie
Driscoll
Secondary
Study
Coordinator
U of Pgh | School
of Medicine |
Medicine
Pitt staff yes
Melanie Driscoll
is a research
coordinator with
the Department
of
Anesthesiology
no
Stephen
Esper
Principal
Investigator
U of Pgh | School
of Medicine |
Anesthesiology
Pitt
faculty
yes
Stephen A.
Esper, MD,
MBA Assistant
Professor of
Anesthesiology-
Co-Investigator,
Remifentanil to
control
hyperglycemia
in cardiac
surgery
no
Arman Kilic
Co-
investigator
Physician Services
Division (UPP and
CMI) | UPP |
Cardiovascular
Institute
Pitt
faculty
yes
Arman Kilic,
MD, Assistant
professor of
cardiothoracic
surgery at the
University of
Pittsburgh
School of
no
 view all 
 view all 

Name
Roles
Department/SchoolAffiliation
Involved
in
Consent
Qualifications
Financial
Interest
Medicine and
director of
surgical quality
an...
Robert
Kormos
Co-
investigator
U of Pgh | School
of Medicine |
Cardiothoracic
Surgery
Pitt
faculty
yes
Robert L.
Kormos, MD,
Professor of
Surgery.
Principal
Investigator,
Long-term
animal survival
with an
implantable
axial flow pump
as a left
ventricul...
no
Caroline
Kostishack
Secondary
Study
Coordinator
Physician Services
Division (UPP and
CMI) | UPP |
Anesthesiology
and Pain Medicine
Pitt staff yes
Caroline Stehle
(nee
Kostishack) is a
clinical
research
coordinator in
the Clinical
Trials Program.
Caroline Stehle
(nee
Kostishack) is
qualified to ...
no
Amy Monroe
Primary
Study
Coordinator
U of Pgh | School
of Medicine |
Anesthesiology
Pitt staff yes
Amy Monroe is
the clinical trials
program
manager. Amy
Monroe is
qualified to
assist with the
informed
consent
process
because she
has completed
the...
no
Penny
Sappington
Co-
investigator
U of Pgh | School
of Medicine |
Critical Care
Medicine
Pitt
faculty
yes
Penny L.
Sappington,
MD, Assistant
Professor,
Critical Care
Medicine. Co-I,
Ethyl Pyruvate:
A Novel
Treatment for
Sepsis”; Co-I,
HMGB1
Alteration Tig...
no
 view all 
 view all 
 view all 
 view all 
 view all 

Name
Roles
Department/SchoolAffiliation
Involved
in
Consent
Qualifications
Financial
Interest
Christopher
Sciortino
Co-
investigator
U of Pgh | School
of Medicine |
Cardiothoracic
Surgery | Cardiac
Surgery
Pitt
faculty
yes
Christopher
Sciortino, MD,
PhD, FACS,
Assistant
Professor of
Cardiothoracic
Surgery at the
University of
Pittsburgh
School of
Medicine and
Surgical D...
no
Kathirvel
Subramaniam
Co-
investigator
U of Pgh | School
of Medicine |
Anesthesiology
Pitt
faculty
yes
Kathirvel
Subramaniam,
MD, MPH,
Associate
Professor of
Anesthesiology-
Principal
Investigator,
Remifentanil to
control
hyperglycemia
in cardiac
surge...
no
Darrell Triulzi Co-
investigator
U of Pgh | School
of Medicine |
Pathology
Pitt
faculty
yes
Darrell J.
Triulzi, MD,
Professor of
Pathology,
Recipient
epidemiology
and donor
study
(REDSIII). This
network will
develop
populations
based
outcome...
no
2. External team member information: (Address all study team members in item
1. above and leave this section blank)
Name
Description
There are no items to display
3. Have you, Stephen  Esper, verified that all members of the research team have
the appropriate expertise, credentials, training, and if applicable, child
clearances and/or hospital privileges to perform those research procedures
that are their responsibility as outlined in the IRB application?
*   Yes  No
 view all 
 view all 
 view all 

View: Pitt SF: Study Scope 8.1
Study Scope
Check all that apply
1. * Will this study actively recruit any of the following populations?
Adults with impaired decision-making capacity

Children (under the applicable law of the jurisdiction in which the research will
be conducted (<18 years for PA))

Children who are Wards of the State

Employees of the University of Pittsburgh/UPMC

Medical Students of University of Pittsburgh as primary research group

Students of the University of Pittsburgh

Neonates of uncertain viability

Non-viable neonates

Non-English speakers

Nursing home patients in the state of Pennsylvania

Pregnant women

Prisoners

N/A
2. * Will any Waivers be requested?
Waiver/Alteration of Consent

Waiver to Document Consent

Waiver/Alteration of HIPAA

Exception from consent for emergency research

N/A
3. * Will this study involve any of the following?

Specimens

Honest Broker to provide data/specimens

Return of Results to Subjects or Others

Fetal tissue
N/A
4. * Will Protected Health Information be collected?

Pitt medical records
UPMC medical records

Other Institutions’ medical records

N/A
5. * Other Requests?

Deception (if not Exempt, also requires Waiver/Alteration of Consent)

Emergency Use / Single Patient Expanded Access (using FDA Form 3926)


Placebo Arm

Withdraw from usual care
N/A
6. * Determining Scientific Review:
Department Scientific Review (this option MUST be picked if there is DoD funding)
* Choose the appropriate organization to conduct the scientific review:
U of Pgh | School of Medicine | Anesthesiology
7. * Has this study (or substantially similar study) been previously disapproved
by the Pitt IRB or, to your knowledge, by any other IRB?
  Yes  No
Review the HRPO policy, if participating in research at the VA Pittsburgh Healthcare
System or using funding from the VA
8. * Does the study use an approved drug or biologic, use an unapproved drug
or biologic, or use a food or dietary supplement to prevent, diagnose, cure,
treat, or mitigate a disease or condition?
  Yes  No
9. * Does the study evaluate the safety or effectiveness of a device (includes in-
vitro laboratory assays)?
  Yes  No
10. * Is this application being submitted to convert an approved study from
OSIRIS to PittPRO? (Tip Sheet)
  Yes  No
Download the OSIRIS Transition Continuing Review form, complete and upload below. If
you need to attach any additional documents (e.g., data and safety monitoring reports),
upload in the Local Supporting Documents page and note the Renewal on the form.
Exempt submissions in OSIRIS also need to move into PittPRO if they remain ongoing.
These will not be considered transitions but new studies. Therefore, Study Scope #10
will be answered as "No." Once the new exempt determination has been issued, the
OSIRIS application can be closed. Any exempt submission remaining in OSIRIS by the
end of August 2020 will be closed by our office. Please use the “Add Comment” to
provide the OSIRIS study number.
OSIRIS Transition Continuing Review form:
Continuing Review Form 2019(0.03)  
* OSIRIS ID
PRO16060542
11. * Does your research protocol involve the evaluation or use of procedures
that emit ionizing radiation and, after reviewing this HUSC guidance, does your
research protocol require HUSC review? (If yes, upload the HUSC form in the
Local Supporting Documents section). If you are unsure of review

requirement, select yes.
  Yes  No
 

View: Pitt SF: Research Sites
Research Sites 
1. Choose all sites that apply:
UPMC
* Select the UPMC sites where research will be conducted:
Presbyterian
2. Describe the availability of resources and the adequacy of the facilities to
conduct this study:
UPMC Presbyterian is a hospital with an Acute Interventional Perioperative Pain
Service (AIPPS). The anesthesiologists here routinely participate in clinical trials and
various other types of clinical research, are well acclimated to conducting clinical
research with respect to good clinical practice. There are sufficient resources of
manpower and supplies to conduct the study

View: Pitt SF: Local Site Documents
Click Continue as this page was intentionally left blank.

View: Pitt SF: Recruitment Methods
Recruitment Methods
* Will you be recruiting individuals for participation in this study?
  Yes  No
1. *  Describe who will be recruiting individuals for participation for this study:
The principal investigator or co-investigator will approach patient with the assistance
of research associates or coordinators if they are conscious and obtain consent.
2. * Select all methods to be used for recruitment:
Directly approaching potential subjects (in-person)
3. * Provide details on your recruitment methods:
Patient will be identified through medical records and operative schedules to
determine study eligibility. The principal investigator or co-investigator will approach
patient with the assistance of research associates or coordinators if they are
conscious and obtain consent. A proxy consent will be obtained in patients who are
unable to provide consent.
4. * Describe all compensation/incentives offered to participants and timing of
these offers:
Patients are not compensated for this study.
5. Recruitment materials: (attach all material to be seen or heard by subjects,
including advertisements and scripts)
 Document
Category
Date Modified
Document History
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View: Pitt SF: Study Aims
Study Aims
1. * Describe the purpose, specific aims, or objectives and state the hypotheses
to be tested:
Specific Aim: A pilot study to evaluate the feasibility and safety of a research
protocol, to evaluate the use of thromboelastography (TEG) in post cardiotomy,
thoraco-abdominal, and trauma surgical patients requiring extracorporeal membrane
oxygenation (ECMO). It is expected that these data will inform a large-scale clinical
trial design. The safety of the TEG protocol will be based upon the amount of
bleeding and thrombotic events.
a. To determine the feasibility and adherence rates of following the protocol for this
trial of TEG for ECMO, and identify potential interventions to improve adherence.
This does not mean that the clinicians are subjects, as the clinicians are already
well-practiced in interpreting TEG as a measure of coagulation and will be using
TEG as a supplement to conventional testing as per study protocol. Further, all
clinicians will follow the same TEG protocol for every patient enrolled in the trial.
The feasibility and safety will be assessed by the number of transfusions that follow
the TEG algorithm, how many patients complete the study, number of TEGs done,
missing or extra TEGs, and number of re-operative events
2. * Describe the relevant prior experience and gaps in current knowledge
including preliminary data. Provide for the scientific or scholarly background
for, rationale for, and significance of the research based on existing literature
and how it will add to existing knowledge:
A study by Shore-Lesserson, et al in 1999 demonstrated that in patients undergoing
cardiac surgery, use of a TEG based transfusion algorithm resulted in less
transfusions than a more traditional algorithm based on ACT, platelet count,
prothrombin time (PT), and PTT. This result was hypothesized to be due to TEG’s
ability to provide qualitative assessment of factor and platelet function, rather than
solely quantitative results (Shore et al). Another recent study by Weber, et al.
demonstrated that the use of rotational thromboelastometry (ROTEM) to guide
hemostatic component therapies was superior to laboratory coagulation testing in
terms of efficacy and cost (Weber et al). It has been shown that use of ROTEM and
TEG is associated with less perioperative blood loss without increases in
transfusions or mortality (Tanaka et al).
A retrospective analysis of 578 patients requiring veno-venous (VV) or VA-ECMO
over the past nine year period at the University of Pittsburgh Medical Center was
accomplished. Data included duration of ECMO, blood products transfused, and
complications from ECMO. The data collected also detailed the transfusion of total
blood products and packed red blood cells for patients on VV and VA ECMO. VA
ECMO appears to be associated with the greatest amount of transfusion, especially
on the day of initiation. Furthermore, in reviewing the data, it appears that the
patients who required VA ECMO had a surgery, generally cardiotomy, prior to
institution of VA ECMO. Resultantly, in many cases, the transfusion of blood
products is generally associated with the day of the primary surgery. This preliminary

data is very important in that it is a guide for the investigators in the determination of
where the greatest impact can be made in terms of reducing blood transfusion in the
operative setting. Because of this data, patients s/p surgery (usually cardiotomy)
appear to have higher incidence of transfusion and as a result, a protocolized and
algorithmic focus is expected to yield a reduction of blood products in this patient
population.
While the use of protocol driven use of TEG in CPB has been described, few studies
have investigated the utility of TEG on the direction of patient care during ECMO for
adult patients. We know that Point-of-care coagulation testing allows for rapid
assessment and goal directed therapy. ROTEM and TEG allow for particularly rapid
results by providing a picture of global coagulation status in around 20 minutes. This
allows for more appropriate and timely transfusion of various blood products,
including red blood cells, platelets, plasma, cryoprecipitate, and clotting factors
(Tanaka et al). We believe the application of algorithmic use of TEG to management
of hemostasis and anticoagulation for patients on ECMO is novel and has the
potential to have a major impact on patient care.
Shore-Lesserson L, Manspeizer H, DePerio M, et al (1999) Thromboelastography-
Guided Transfusion Algorithm Reduces Transfusions in Complex Cardiac Surgery.
Anesth Analg 88, 312-19
Tanaka K, Bolliger D, Vadlamudi R, et al (2012) Rotational Thromboelastometry
(ROTEM)- Based Coagulation Management in Cardiac Surgery and Major Trauma.
J of Cardiothoracic and Vascular Anesthesia 26, 1083-93
Weber C, Gorlinger K, Meininger D, et al (2012) Point-of-Care Testing: A
Prospective, Randomized Clinical Trial of Efficacy in Coagulopathic Cardiac Surgery
Patients. Anesthesiology 117(3), 531-47
 

View: Pitt SF: Study Design
Study Design
1. Total number of subjects to be enrolled at this site (enter -1 for chart reviews,
banking, registries):
100
2. Describe and explain the study design:
The proposed study design is single center, prospective, pilot clinical trial
3. Describe the primary and secondary study endpoints:
Primary outcome variable- Determine the feasibility of following the protocol for this
trial of TEG for ECMO.
Secondary outcome variable- Assess clinical outcomes including the rates of
transfusion, major bleeding, and major complications in patients on ECMO managed
with TEG in addition to traditional laboratory measures of coagulation.
4. Provide a description of the following study timelines:
Duration of an individual subject's active participation:
30 days
Duration anticipated to enroll all subjects:
1 year
Estimated date for the investigator to complete this study (complete primary
analyses): 
12/1/2020
5. List the inclusion criteria:
Adult patient requiring ECMO
6. List the exclusion criteria:
Children less than 18 years of age
7. Will children or any gender, racial or ethnic subgroups be explicitly excluded
from participation?
  Yes  No
* Identify the subgroups and provide a justification: 
Children less than 18 years of age as only adults are seen at this institution
8. Describe the power analysis used and cite your method of statistical analysis.
If a power analysis is not possible, thoroughly justify the sample size required
for the study, including appropriate literature citation (alternatively provide
page reference in attached protocol):
Approximately 100 ECMO cases are seen per year in the UPMC Presbyterian

Hospital, of which, approximately 50% require VA-ECMO. We expect to enroll 50-
60% of those patients per year. Regarding Specific Aim 1: Feasibility will be defined
by a minimum of 80% of patients who will have followed the algorithm on greater
than or equal to 90% of the days on ECMO.The data obtained from this pilot and
feasibility study will help to establish event rates, transfusion rates and volumes, to
inform subsequent larger clinical trialsIncidence of protocol compliance will be
analyzed by Chi Square test or Fisher exact test. P value less than 0.05 will be
considered significant. Transfusion rates and volumes as well as clinical outcome
rates will be analyzed by independent-sample t test or Mann Whitney U test
wherever appropriate.

View: Pitt SF: Cognitively Impaired Adults
Cognitively Impaired Adults
1. *  Provide a justification for the inclusion of adult subjects who are unable to
provide direct consent for study participation:
A large proportion of patients will undergo ECMO in an emergent setting, in which
they themselves are unable to provide consent due to their clinical status. Once it is
determined by an investigator that the patient is unable to provide consent, consent
will be obtained from the patient's proxy.
2. *  Specify the criteria used to determine that a given potential adult subject is
not able to provide direct consent for participation and identify who will
responsible for that determination:
If a patient is heavily sedated, unconscious or intubated they will not be able to
provide consent and a investigator will make the determination to approach the
Proxy for consent.

View: Pitt SF: Research Activities
Research Activities
1. * Provide a detailed description of all research activities (including screening
and follow-up procedures) that will be performed for the purpose of this
research study. This description of activities should be complete and of
sufficient detail to permit an assessment of associated risks.
Once the patient is placed on ECMO, baseline arterial blood gas (ABG), complete
blood count (CBC), fibrinogen, platelet count, aPTT, PT and TEG will be performed.
Simultaneous heparinase and kaolin TEG must be performed any time a TEG is
performed. Pertinent TEG results will include: heparinase-kaolin TEG maximum
amplitude (MA) in millimeters (mm), heparinase-kaolin TEG r-time in seconds,
heparinase-kaolin TEG alpha angle in degrees, and TEG functional fibrinogen
(FLEV) MA in mm. These tests will be performed by a perfusionist in the operating
room under the oversight of a co-investigator or principal investigator.
For all patients, the above tests will be performed per the algorithm described in
Flowcharts 1 and 2 (attached). Flowchart 1 describes transfusion algorithm for
patients in the operating room with inadequate hemostasis, >4 cc/kg/hour. Flowchart
2 describes transfusion management in the ICU when bleeding is less than <4
cc/kg/hour.
Once patient has a normal TEG result with adequate hemostasis, either heparin or
bivalirudin will be used as the anticoagulant. Transfusion parameters as described
above will only be used on patients who are received no anticoagulation or heparin
anticoagulation. If patients are receiving bivalirudin as their anticoagulation strategy,
the transfusion parameters with TEG application will not apply.
Heparin titration will be based on kaolin TEG r-time, MA, alpha angle and anti-xa.
Transfusion parameters will be based on heparinase TEG results, INR, platelet
count, fibrinogen, and CBC per study protocol.
CTICU heparin titration nomogram:
antiXa/TEG/ACT Action
≤0.20 units/ml and r-time < 10 minutes
-Increase infusion rate by 2 units/kg/hour
-Repeat STAT anti-Xa/TEG 6 hours after rate change
**If the anti-Xa AND TEG do not agree, contact investigator and defer to anti-Xa
nomogram for treatment
0.21-0.24 units/ml and
r-time >10 minutes but ≤15 minutes -Increase infusion rate by 1 units/kg/hour
-Repeat STAT anti-Xa/TEG 6 hours after rate change
**If the anti-Xa AND TEG do not agree, contact investigator and defer to anti-Xa
nomogram for treatment

0.25-0.35 units/ml and r-time >15 but less than 25 minutes and angle between 20
and 50
(therapeutic range) -No changes in infusion rate
-Repeat STAT anti-Xa/TEG every 6 hours for two consecutive results
If therapeutic, order STAT anti-Xa/TEG daily
**If the anti-Xa AND TEG do not agree, contact investigator and defer to anti-Xa
nomogram for treatment
0.36-0.45 units/ml and r-time >25 minutes and angle <30 -Decrease infusion rate by
1 unit/kg/hour after this hour
-Repeat STAT anti-XaTEG 2 hours after rate change
**If the anti-Xa AND TEG do not agree, contact investigator and defer to anti-Xa
nomogram for treatment
0.46-0.069 units/ml and r-time >30 minutes and angle < 25 -Hold heparin infusion
for 1 hour
-Decrease Infusion rate by 2 units/kg/hour after this hour
-Repeat STAT anti-Xa/TEG 2 hours after rate change
**If the anti-Xa AND TEG do not agree, contact investigator and defer to anti-Xa
nomogram for treatment
≥ 0.70 units/ml and no sign of TEG clotting -Hold heparin infusion for 2 hours
-Decrease infusion rate by 6 units/kg/hour after 2 hours
-STAT aPTT/TEG 2 hours after rate change
**If the anti-Xa AND TEG do not agree, contact investigator and defer to anti-Xa
nomogram for treatment
TEG anticoagulant parameters based upon:
48. Schears GA. Personal Communication from Dr. Greg Schears from Mayo Clinic
from retrospective data analysis. 2014; November.
In addition to using the anti-xa level per the CTICU heparin nomogram as detailed
above, TEG will also be used to help manage the anticoagulation, based on kaolin
TEG r-time and alpha angle. Goals are set as: TEG r-time between 15 and 20
minutes and TEG alpha angle between 30 and 50 degrees. Heparinase and kaolin
TEGs will be drawn each time. The heparinase and kaolin TEGs drawn will be able
to show a more complete picture of coagulation, in that the heparin effect will be
removed (while a patient is receiving heparin for anticoagulation) and underlying
coagulopathy can be treated if found. Further, kaolin TEGs, while patients are
receiving heparin, will be used for further anticoagulation management, as
discussed above.
NOTE: While the ACT is not used at our institution for guiding anticoagulation
therapy, many hospitals use this as the only anticoagulation guide. Thus, it would be
appropriate to compare anti-xa as well as TEG to the ACT for the gathering of
further data. Each time an anti-xa and TEG is drawn per the protocol, an ACT will
also be drawn for study purposes.

Transfusion Parameters:
 Hematocrit <22.5% or Hemoglobin <7.5 g/dl  transfuse 2 units PRBC and
recheck CBC
 Platelet Count <100,000/ul or heparinase TEG MA <50 mm  transfuse 1 dose of
platelets
 Signs of bleeding and heparinase TEG r-time >20 mm and an INR > 2.0 with
clinical signs of bleeding transfuse 4 units of FFP
 Signs of bleeding and Fibrinogen <180 mg/dl and heparinase TEG angle less than
30 mm  1 dose cryopercipiate (4units = 2.0 grams fibrinogen)
TEG transfusion parameters based upon:
48. Schears GA. Personal Communication from Dr. Greg Schears from Mayo Clinic
from retrospective data analysis. 2014; November.
44. Shore-Lesserson L, Manspeizer H, DePerio M, et al (1999)
Thromboelastography-Guided Transfusion Algorithm Reduces Transfusions in
Complex Cardiac Surgery. Anesth Analg 88, 312-19.
The following parameters will specifically be investigated/recorded:
- Patient characteristics (sex, age, indication for ECMO, VV or AV ECMO,
cannulation sites)
- Chest tube output and overall estimated blood loss
- Pre-ECMO/Pre-operative anticoagulation, including heparin, low molecular weight
heparin, and other anti-aggregants including cyclooxygenase inhibitors such as
aspirin, adenosine diphosphate receptor inhibitors such as clopidogrel, Glycoprotein
IIB/IIIA (GpIIb/IIIa) inhibitors, phosphodiesterase inhibitors, adenosine reuptake
inhibitors, and thromboxane inhibitors.
- Number of transfusions required while on ECMO (primary outcome)
- Time between transfusions
- Type of products transfused
- Pump exchanges required
- Oxygenator exchanges
- Occurrence of pump circuit clotting and clots in the oxygenator (visible clot which
did not require circuit/pump exchange)
- Time to weaning from/removal of ECMO
- Need for surgical intervention for hemorrhage
- Occurrence of clinical thrombotic or hemorrhagic event (stroke for example)
- Specimen turn-around time for standard labs tests (CBC, ACT, PT, PTT, anti-Xa,
INR, platelet count) and TEG results
Data will be collected for each enrolled patient until they are discontinued from
ECMO.
2. Upload a copy of all materials used to collect data about subjects: (Attach all
surveys, interview/focus group scripts, and data collection forms except for
case report forms, SCID or KSADS):
 Document
Category
Date Modified
Document History
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3. * Will blood samples be obtained for research purposes?
  Yes  No
* Provide the volume per withdrawal, total volume and frequency,
and qualifications of individual performing the procedure:
Blood drawn from the patient will come out of a pre-existing arterial line and will
include a 1.0 ml syringe every 2-6 hours, depending on the value of the previous
TEG and other standard of care tests (arterial blood gas, complete blood count,
fibrinogen, platelet count, anti-xa). Patients will have on average 15 TEGs drawn
over the course of the trial, for a total of 15ml of blood drawn for this study.
 

View: Pitt SF: Consent Process
Consent Process
Enter N/A in response to the following questions if a Waiver of Consent is requested for all
research activities or if no subjects are being enrolled.
1. * Indicate where the consent process will take place and at what point
consent will be obtained:
The informed consent process will take place in the hospital pre-operative area prior
to performing any of the research interventions/interactions.
2. * Describe the steps that will be taken to minimize coercion and undue
influence, including assurance that there is sufficient time for subjects to
make an informed decision:
In order to minimize the possibility of coercion or undue influence, the patients will
be first informed that the choice of participation in the study is totally voluntarily in
nature, and they will receive the standard of care when they decide not to participate
in the study. Prospective patients will be encouraged to ask questions and to discuss
the study with others during the consent process.
3. For studies that involve multiple visits, describe the process to ensure
ongoing consent:
Not applicable
4. * Steps to be taken to ensure the subjects’ understanding:
The physician investigator will have a discussion about the possibility of being a
study participant with the patient/proxy several days to several hours prior to the
surgery. The risk, benefits and goals of the study will be presented to the patient. On
the day of the surgery, prior to any study procedures, if the patient is agreeable to
participation in the study, the patient will sign consent to participate in the study.
If the patient is unconscious, the physicians will review medical record for
responsiveness and will consult with one another to determine patient is truly not
able to provide consent. In this instance, a proxy will be approached to provide
consent.
5. * Are you requesting an exception to the IRB policy related to the informed
consent process:
  Yes  No
Since participants with impaired decision-making capacity to consent will be
enrolled, address the following questions:
* Describe the process for identifying the appropriate person to act as proxy
for the participant:
The research staff will look to see who signs the surgical and anesthesia consent on
the patient's behalf. The Principal Investigator will then take jurisdiction to ensure
that person is in fact the patient's legally authorized representative.
If a Legally Authorized Representative already exists for the patient, study

investigators will confirm legality of the proxy and approach that person for consent.
If no LAR is named, study investigators will seek informed consent from the
following individuals, in this order: natural or adoptive parent; adult child; adult
brother or sister; any other available adult relative related through blood or marriage
known and documented to have made decisions for the subject in prior health care
settings etc.
* Will assent be obtained from the participant who has impaired decision-
making capacity?
  Yes  No
* Justify why their assent will not be sought:
If a patient is cognitively available to give assent, then they also would be able to
give informed consent and so obtaining assent would not be necessary

View: Pitt SF: Consent Forms
Consent Forms 
1. Consent Forms:
 
Document
Category
Date Modified
Document History
View Consent Form(0.01)
Consent Form
8/22/2019
History
Refer to the following templates and instructional documents:
Guidance - Consent Wording
Template - Consent Document - Short Form
HRP-090 - SOP - Informed Consent Process for Research  
HRP-091 - SOP - Written Documentation of Consent  
 

View: Pitt SF: Waiver/Alteration of Consent
Waiver/Alteration of Consent
1. * Select all options that apply to the request to waive the requirement to
obtain informed consent:
Review of identifiable medical records
General Requirements: The Federal Policy (45 CFR 46.116 (d)) as well as guidance
issued by the FDA requires the following criteria to be met for a waiver or alteration of
consent to be approved with one exception.The FDA does not include a biospecimen
provision (Item #4 below). You MUST provide a justification addressing how each of the
criterion are met for each option chosen in Item #1.
2. * The research involves no more than minimal risk to the subjects;
To enroll patients into the study, medical records of potential subjects will be
reviewed. The medical record will be reviewed and if the patient is eligible, further
consent process will be followed. If the patient is not eligible, patient's data will not
be stored in the study database except the number of patients screened will be
entered and stored within the UPMC firewall in a password protected file and drive
3. * The waiver or alteration will not adversely affect the rights and welfare of the
subjects;
Medical record review and further eligibility into the study will not affect the patient's
right to any standard therapy and welfare of subjects in anyway. If the patient is not
eligible, they will receive standard perioperative therapy by anesthesia/ surgery and
patient care team. Dr. Esper and other anesthesia team members of the study may
provide anesthesia/surgical care/ECMO even if the patient's are ineligible for the
study and follow the standard of care
4. If the research involves using identifiable private information or identifiable
biospecimens, the research could not practicably be carried out without using
such information or biospecimens in an identifiable format (enter N/A for FDA
regulated studies);
Identification of potential subjects can be done by speaking with all potential
subjects or by selectively identifying potentially eligible patients through medical
record review. Medical record review will avoid speaking with all patients who may
or may not require ECMO after their surgery. But any medical record review by a
physician not directly involved in the patient care requires waiver of consent, Without
this waiver, we cannot identify potential research subjects
5. * The research could not practicably be carried out without the waiver or
alteration;
We cannot feasibility approach every patient who is having surgery without
determining if they qualify beforehand.
6. * Whenever appropriate, the subjects will be provided with additional
pertinent information after participation;
We will not acquire any information that will be pertinent to the participant's care

since this Waiver only applies to the this limited recruitment procedure. Only
eligibility criteria (inclusion and exclusion criteria) of the patients will be reviewed. No
other personnel or individual patient care information will be reviewed
7. * Under what circumstances (if any) will you obtain consent from some of
these subjects:
A preliminary and limited assessment of patients medical charts will occur just to
exclude patients with clear and certain exclusion criteria. Medical records will be
reviewed under a waiver of consent for all subjects. They will provide informed
consent prior to enrolling in the study.

View: Pitt SF: Medical Records
Medical Records
1. You are required to submit this study to the Research Informatics Office, Health
Record Research Request (R3). Per UPMC Policy HS-RS0005, all research
projects that access or involve UPMC electronic protected health information (e-
PHI) must be submitted to R3, with the exception of clinical trials that are
contracted through the UPMC Office of Sponsored Programs and Research
Support (OSPARS).
Complete the R3 intake form available at http://rio.pitt.edu/services. An R3
representative will conduct a review. You will be notified once your R3 review is
complete or if anything further is needed.
* Describe the protected health information that will be collected from the
covered entity and/or the research derived information that will be placed into
the medical records:
Patient characteristics (sex, age, indication for ECMO, VV or AV ECMO, cannulation
sites), chest tube output and overall blood loss, Pre-ECMO anticoagulant drug
therapies, number of transfusions required while on ECMO, time between
transfusions, type of products transfused, pump exchanges required, oxygenator
exchanges, occurrence of pump circuit clotting and clots in the oxygenator, time to
weaning from/removal of ECMO, need for surgical intervention of hemorrhage,
occurrence of clinical thrombotic or hemorrhagic event, specimen turn-around time
for standard labs (CBC, ACT, PT, PTT, anti-Xa, INR, platelet count) and TEG result
will be collected from the time patient is enrolled in the trial until ECMO is
discontinued.

View: Pitt SF: Electronic Data Management
Electronic Data Management
1. * Will only anonymous data be collected (select NO if identifiers will be
recorded at anytime during the conduct of the study)?
  Yes  No
Select all identifiers to be collected during any phase of the research including
screening:
Name:

E-mail address:

Social security #:

Phone/Fax #:

Account #:

Medical record #:

Certificate/license #: 
 
 
Internet Protocol (IP) Address:

Web Universal Resource Locators (URLs):

Social security # (for Vincent payment only):

Full face photo images or comparable images: 
Health plan beneficiary #:

Device identifiers/serial numbers:

Vehicle identifiers/serial #/license plate #:

Biometric identifiers, finger and voice prints:

* 
a: Will you be collecting any of the following location data: geographic subdivisions smaller
than a State such as street address, city, county, precinct, zip, geocodes, etc.?
 
  Yes  No
* b: Will you be collecting any date information such as birth date, death, admission,
discharge, date of surgery/service?
  Yes  No
c: List any other unique identifying numbers, characteristics or codes related to an
individual that are to be collected:
d: Will you be collecting any data subject to the General Data Protection Regulation (GDPR)?   Yes  No
* 
For ALL identifiable data collected, will
you be coding the data by removing the
identifiers and assigning a unique
study ID/code to protect the identity of
the participant?
  Yes  No
* Will the data be HIPAA de-identified?
  Yes  No

* 
Briefly describe your plan to store
coded data separately from the
identifiable data:
Identifiable data will be kept in a
single encrypted file on the shared (z:)
drive behind the UPMC firewall. All
other study-related data (such as
paper records and data for analysis)
will have all identifiers removed. To
protect against the possibility of
breach of confidentiality, all data
collected will be identifiable only by an
unique subject ID number, and no
personal identifiers will be stored with
the data. Linkage files identifying
subjects will be stored only in the
UPMC server and will be linked to the
physical record with a subject code.
Physical records will be kept in locked
files accessible only by study staff;
electronic data will be handled and
protected as described above on the
UPMC server.
2. During this study, will restricted data as defined by the University’s Data Risk
Classification matrix ( https://www.technology.pitt.edu/security/data-risk-
classification-and-compliance ) be processed, stored, or transmitted?
  Yes  No 
3. * During this study, will sensitive data (https://www.hrpo.pitt.edu/electronic-data-
security) be collected where disclosure of identifying information could have
adverse consequences for subjects or damage their financial standing,
employability, insurability, educational advancement, reputation or place them
at risk for criminal or civil liability?
  Yes  No
4. * Select all locations where data will be stored or archived(including e.g.,
personal / employer laptop or desktop): If you have access to University owned
or controlled resources, facilities, or repositories, such as computer servers,
please choose that option to comply with the Research Data Management
Interim Policy R1 14.
Please note that to address Research Security Requirements, University data
must be stored in University owned, controlled, or approved repositories,
such as Pitt OneDrive. If UPMC or external electronic repositories must be
used, they must be approved by Pitt IT.
 
Storage Device
DescriptionIdentifiable
Data
Sensitive
Data
De-
Identified/Anonymous
Data
View
UPMC:
Departmental or
Hospital Server 
 
yes
yes
yes
View
UPMC owned
desktop, laptop or
other device
 
no
no
no
5. * Select all technologies being used to collect data or interact with
subjects: Technologies selected in this section may require a Vendor Security

Risk Assessment, which can be requested here.
N/A

View: Pitt SF: Data Safety and Monitoring
Data Safety and Monitoring
1. * Describe your plan to periodically evaluate the data collected regarding both
harms and benefits to determine whether subjects remain safe.  The plan
might include establishing a data monitoring committee and a plan for
reporting data monitoring committee findings to the IRB and the sponsor:
The following data and safety monitoring plan will be instituted to ensure the safety
of the subjects and to maintain the confidentiality of the research data. The principal
investigator, co-investigators and study coordinators will perform monthly or
quarterly reviews of the accrued data and incidence of adverse effects to ensure
validity and integrity of the data and to reassess the benefit-to-risk ratio on a
frequent and regular basis. Subject privacy and research data confidentiality will be
ensured by reviewing the adequacy of the secure location of where the data is
stored and by making sure it is all de-identified with the coded case numbers as
described previously. Adverse events, data quality and timeliness of participant
recruitment will all be reviewed with the team of investigators, who will determine
whether the study should be continued as planned, changed or terminated.
2.   * Describe your plan for sharing data and/or specimens:
No data sharing is planned.
3. If any research data is collected, stored, or shared in a paper format, address
what precautions will be used to maintain the confidentiality of the data:
Paper-based records will be kept in a secure location, computer-based files will be
available to personnel involved in the study through access privilege, whenever
possible identifiers will be removed from study-related information, patients'
computer medical information will only be available through password access.

View: Pitt SF: Risk and Benefits
Risk and Benefits
1. *  Enter all reasonably foreseeable risks, discomforts, hazards, or
inconveniences to the subjects related to subjects’ participation in the
research:
View
Research Activity
Review of Medical Records 
Common Risks
No Value Entered 
Infrequent Risks
No Value Entered 
Other Risks
Breach of confidentiality.  
View
Research Activity
Blood Draw From Arterial Line 
Common Risks
No Value Entered 
Infrequent Risks
No Value Entered 
Other Risks
No Value Entered 
View
Research Activity
TEG Interpretation 
Common Risks
No Value Entered 
Infrequent Risks
No Value Entered 
Other Risks
It is possible that incorrect interpretation of TEG results could lead to
mismanagement of coagulation therapy.  
2. *  Describe the steps that will be taken to prevent or to minimize risks:
All investigators who will access the identifiable medical records already have
normal clinical access to all necessary records, as granted by the privacy office for
job-related needs. Thus, only HIPAA trained research staff will be handling this
information and this information will be stored in a locked database protected by the
UPMC firewall. Additionally, all data generated under this protocol will be monitored
and maintained by the principal investigator. Any databases that contain identifiable
information will be stored on a departmental drive on the UPMC network created for
the principal investigator, and all data will be deidentified according to the HIPPA
"safe harbor" guidelines prior to statistical analysis.
In order to avoid coagulation mismanagement as the result of a misinterpreted TEG
result, traditional standard of care coagulation testing will also be done (anti-Xa,
ACT) in conjunction with the TEG and will be the driving force in coagulation
management.
Arterial line blood draws will be limited to the lowest number possible based on
previous TEG and conventional test values. The average patient will have a
maximum of 15 blood draws over the duration of the trial.

3. Financial risks - will the subject or insurer be charged for any research
required procedures?
  Yes  No
*  Address each procedure with a justification and indicate if charges are
incurred for investigational drugs/devices. Address, if applicable, a
contingency plan for those not able to cover the cost of participation:
Charges will be billed only for procedures performed as part of the subject's routine
clinical care.
4. Describe the steps that will be taken to protect subjects’ privacy:
Research intervention will be conducted in a private room with the patient, collected
information will be limited to that which is necessary for the goals of the research
study, access to the patient's private information will be limited to those involved in
the patient's medical care.
5. What steps will be taken in the event that a clinically significant, unexpected
disease or condition is identified during the conduct of the study:
The patient's primary medical team will be immediately notified of the unexpected,
clinically significant condition. The patient's clinically significant medical condition will
be managed accordingly. If any of the clinically significant medical condition is
related to the study, then the patient's participation in the study will be re-evaluated,
with the possibility of the patient being withdrawn from the study if this leads to the
resolution of the clinically significant medical condition.
6. Describe the potential benefit that individual subjects may experience from
taking part in the research or indicate if there is no direct benefit. Do not
include benefits to society or others:
There is no direct benefit to the subjects.
7. Do you anticipate any circumstances under which subjects might be
withdrawn from the research without their consent?
  Yes  No
8. Describe procedures that will be followed when subjects withdraw from the
research, including partial withdrawal from procedures with continued data
collection and data already collected:
After withdrawing from the study, each subject's data will be kept for the required
data retention period in a secure, locked facility, and will be destroyed after that
period. Patients' data might be used for data analysis if deemed necessary/useful
(e.g. reason of withdrawal).

View: Pitt SF: Conflict of Interest Ver2
Conflict of Interest
Institutional Financial Interests
1. * To the best of your knowledge, has the University of Pittsburgh optioned or
licensed technology that will be tested or evaluated in this research?
  Yes  No

View: Pitt SF: Ancillary Reviews
Ancillary Reviews 
1. Ancillary reviews or notifications selected below are required based on
previous answers to questions. If a selection is incorrect, return to the
appropriate page and adjust the answers to questions on that page: 
  Conflict of Interest (COI)
  Clinical and Translational Research Center (CTRC)
  Data Security
  Honest Broker
  UPMC Investigational Drug Service
  Pitt Medical School Review
 Pitt+Me  
  IND & IDE Support(IIS)
  Radioactive Drug Research Committee (RDRC)(study involves the evaluation
or use of procedures that emit ionizing radiation)
  ORP Business Manager (required for industry sponsored studies)
  Religious Directives
  Scientific Review
  Health Record Research Request (R3) (required if using UPMC clinical data
and authorization for other UPMC data sources for research)
  UPMC Office of Sponsored Programs and Research Support (using UPMC
facilities and/or UPMC patients during the conduct of the study)
2. Additional ancillary reviews the PI may choose to include as needed for the
research:
  Human Stem Cell Oversight (hSCRO)
  Institutional Biosafety Committee (IBC)(study involves deliberate transfer of
recombinant or synthetic nucleic acid molecules)

View: Pitt SF: Clinical Trials
Good Clinical Practice (GCP) Training
1. * Regardless of funding source, is this study a clinical trial (as defined by the
NIH)?
  Yes  No
ClinicalTrials.gov Information
Visit the University of Pittsburgh Office for ClinicalTrials.gov website or contact ctgov@pitt.edu
for further information.  
2. * Was this study registered, or will it be registered, on ClinicalTrials.gov?
  Yes  No
3. * Is the University of Pittsburgh or UPMC the Sponsor Organization for this
study record?
  Yes  No 
* Who will be the Responsible Party for this study record?
Principal Investigator of this IRB application

View: Pitt SF: Supporting Documents
Supporting Documents
1. Attach any additional supporting documents not previously uploaded. Name
the documents as you want them to appear in the approval letter:
 
Document
CategoryDate
Modified
Document
History
View Esper ECMO
references(0.01)
Other
8/22/2019
History

View: Pitt Create
Add Storage Information
1. * Select a Storage Type:
UPMC: Departmental or Hospital Server 
2. Description:
3. * Will identifiable data be stored in this location?
  Yes  No
4. * Will sensitive data be stored in this location?
  Yes  No
5. Will de-Identified or anonymous data be stored in this location?
  Yes  No
6. Provide additional information as needed:

View: Pitt Create
Add Storage Information
1. * Select a Storage Type:
UPMC owned desktop, laptop or other device
2. Description:
3. * Will identifiable data be stored in this location?
  Yes  No
4. * Will sensitive data be stored in this location?
  Yes  No
5. Will de-Identified or anonymous data be stored in this location?
  Yes  No
6. * Is anti-virus software installed and up to date on all devices and are the
operating systems kept up-to-date on all devices?
  Yes  No
7. Provide additional information as needed:

View: Pitt Risk
Risk
1. * Research Activity:
Review of Medical Records
2. Common Risks:
3. Infrequent Risks:
4. Other Risks:
Breach of confidentiality.

View: Pitt Risk
Risk
1. * Research Activity:
Blood Draw From Arterial Line
2. Common Risks:
3. Infrequent Risks:
4. Other Risks:

View: Pitt Risk
Risk
1. * Research Activity:
TEG Interpretation
2. Common Risks:
3. Infrequent Risks:
4. Other Risks:
It is possible that incorrect interpretation of TEG results could lead to
mismanagement of coagulation therapy.