Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD
Phase: NA
Conditions: Heart Failure
Sponsor: Massachusetts General Hospital

Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD  
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PI: David D’Alessandro, MD 
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PARTNERS HUMAN RESEARCH COMMITTEE  
DETAILED PROTOCOL 
 
 
Percutaneous RVAD to Preemptively Treat Right Heart 
Failure Post-LVAD 
 
Protocol 2020P000422 / NCT04458103 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
_____________________________________________________________________________________ 
I. TABLE OF CHANGES .......................................................................................................................... 3 
II.ABBREVIATIONS, ACRONYMS, DEFINITIONS ........................................................................... 3 
II. BACKGROUND AND SIGNIFICANCE ............................................................................................ 4 
III. SPECIFIC AIMS .................................................................................................................................. 6 
IV. SUBJECT SELECTION ...................................................................................................................... 6 
INCLUSION:........................................................................................................................................... 7 
EXCLUSION: ......................................................................................................................................... 7 
V. SUBJECT ENROLLMENT .................................................................................................................. 7 
VI. STUDY PROCEDURES ...................................................................................................................... 9 
VII. DATA COLLECTION SCHEDULE .............................................................................................. 10 
VIII. BIOSTATISTICAL ANALYSIS .................................................................................................... 11 
STUDY VARIABLES ........................................................................................................................... 11 
PRIMARY ENDPOINT ....................................................................................................................... 12 
SECONDARY OUTCOMES ............................................................................................................... 12 
POWER ANALYSIS ............................................................................................................................ 12 
IX. RISKS AND DISCOMFORTS .......................................................................................................... 13 
X. POTENTIAL BENEFITS ................................................................................................................... 13 
XI. MONITORING AND QUALITY ASSURANCE ............................................................................ 14 
XII. REFERENCES .................................................................................................................................. 15 
 
 
 
 
 
 
 
 
 
 

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I. 
TABLE OF CHANGES 
 
VERSION / DATE 
SUBSECTION 
CHANGE/RATIONALE 
2 / July 14, 2020 
Title 
Remove “preoperative” from title to 
reflect protocol changes allowing for 
concomitant RVAD placement to LVAD 
implantation. 
2 / July 14, 2020 
Background and Significance; 
Specific Aims; 
Subject Selection; 
Subject Enrollment; 
Study Procedures; 
Biostatistical Analysis; 
Potential Benefits 
Timing of percutaneous RVAD placement 
changed to allow for intraoperative 
placement in addition to pre-operative 
placement. 
3 / March 5, 2021 
Cover Page 
Add IRB protocol number and NCT 
number to protocol cover page. 
3 / March 5, 2021 
Table of Changes 
Add table of changes to reflect 
amendments to protocol. 
3 / March 5, 2021 
Subject Selection 
Remove “severe tricuspid regurgitation in 
a patient where a valve intervention is 
expected” and “known or expected PFO 
closure” from exclusion criteria based on 
amended protocol allowing for 
concomitant percutaneous RVAD 
placement, therefore allowing valve 
intervention or PFO closure to occur prior 
to RVAD placement, no longer impeding 
safe placement of the device. 
3 / March 5, 2021 
Data Collection Schedule 
Update data collection schedule to reflect 
that RVAD placement can occur 
concomitantly to LVAD implantation 
 
II. 
ABBREVIATIONS, ACRONYMS, DEFINITIONS 
 
AKI – Acute Kidney Injury 
ALT- Alanine Aminotransferase 
AST – Aspartate Aminotransferase  
CBC – Complete Blood Count 
CI – Cardiac Index 

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CMP – Comprehensive Metabolic Panel 
CVP – Central Venous Pressure 
EDC – Electronic Data Collection 
EKG – Electrocardiogram  
ICU – Intensive Care Unit 
INR – International Normalized Ratio 
IRB – Institutional Review Board 
IVC- Inferior Vena Cava 
LOS – Length of Stay 
LVAD- Left Ventricular Assist Device 
MGH – Massachusetts General Hospital 
PA - Pulmonary Artery  
PI – Principal Investigator 
RIJ – Right Internal Jugular  
RVAD – Right Ventricular Assist Device 
RVF – Right Ventricular Failure 
SAE – Serious Adverse Event 
sCr – Serum Creatinine 
VIS – Vasoactive Inotrope Score 
 
 
 
 
II. BACKGROUND AND SIGNIFICANCE 
 
Prior studies have shown that left ventricular assist device (LVAD) implantation commonly 
results in right ventricular failure (RVF) due to changes in septal positioning and the left heart 
cardiac output returning to normal, causing acute right ventricular overload. Right ventricular 
dysfunction and failure after LVAD implantation is known to increase morbidity and mortality 
and contribute to longer post-implant hospital length of stay. More severe right ventricular 
failure is highly correlated with poor prognosis and death post-LVAD implantation (Kang).  

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In current practice, patients who receive LVADs require right heart support, provided in the form 
of inotropes. Additionally, the operational speed of the newly implanted LVAD is typically 
purposely low for the first 24 – 48 hours to reduce the negative impact on RV geometry and 
function. Vasoactive inotrope score (VIS) is a measure that quantifies the amount of right heart 
support required post-operatively, including dopamine, dobutamine, milrinone, epinephrine, 
norepinephrine, and vasopressin. It has been used in other studies as a surrogate marker for 
hemodynamic cardiovascular derangement (Han). The use of 2 or more inotropic agents has been 
found to be correlated with a higher right atrial to pulmonary capillary wedge pressure ratio and 
a lower pulmonary artery pulsatility index when compared with 0-1 agents. This means that a 
higher VIS is correlated with right heart dysfunction (Morine). The use of two or more 
vasopressors or inotropes is also correlated with worsening of biomarkers such as higher 
creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (Morine). 
Therefore, greater use of vasopressors and inotropes could be associated with end organ 
dysfunction. Higher VIS is also associated with increased hospital mortality (Na).  
In some cases, right ventricular failure post-LVAD also requires mechanical circulatory support 
during the perioperative period. When used, these devices allow for rapid down titration of 
inotropic support and an increase in LVAD operation speed and therefore systemic perfusion. 
Newer generation, percutaneous assist devices are now available and can be positioned in the 
right ventricle providing up to 4.5 L/min of support. Several attempts have been made to create 
calculations to predict RVF in LVAD patients, with little success (Salna). Since RVF is difficult 
to predict and can have harmful effects such as increased ICU stay, adverse outcomes, and 
mortality (Anderson), it could be beneficial to preemptively treat patients through preoperative 
or intraoperative percutaneous right ventricular assist device (RVAD) placement to prevent RVF. 
The purpose of this study is to test the hypothesis that preemptive use of percutaneous RVADs 
will mitigate the need for inotropic support in LVAD patients, reducing associated adverse 
outcomes. 
There are two types of percutaneous RVADs that will be used in the study: the Impella RP and 
the ProtekDuo. These devices allow for early intervention in RVF without the need for invasive 
surgical procedures requiring placement of durable RVADs via thoracotomy or sternotomy. 
Unplanned reoperation and implantation of surgical RVADs is associated with higher morbidity 
and poor outcomes (Salna). The use of percutaneous RVADs to prevent RVF requiring 
reoperation and durable RVADs therefore may be a safer alternative that yields better outcomes. 
The objective of this prospective study is to assess whether RVAD placement in patients prior to 
or during LVAD implantation leads to a mitigated need for vasoactive inotropic support and 
improved end organ function compared with standard of care LVAD implantation in the absence 
of percutaneous RVAD placement. 
The Impella RP, manufactured by Abiomed, is a heart pump that delivers blood from the inferior 
vena cava (IVC) to the pulmonary artery (PA). Its insertion is done percutaneously via 
catheterization through the femoral vein. The use of the Impella RP device is often used for the 
management of RVF post-LVAD placement. In these patients, hemodynamics have been shown 
to improve immediately after Impella RP initiation. This includes an increase in cardiac index 

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(CI), which results in the improvement of systemic and end-organ perfusion, as well as the 
reversal of cardiogenic shock. Impella RP placement has also been shown to decrease central 
venous pressure (CVP) (Anderson). This improvement in hemodynamics facilitates the weaning 
of inotrope and vasopressor support. LVAD flow has also been shown to improve after Impella 
RP support is initiated (Anderson). 
ProtekDuo, manufactured by TandemLife, is another device placed percutaneously for right 
heart support via the right internal jugular (RIJ) vein. Like the Impella RP, use of the ProtekDuo 
is associated with improved hemodynamics in patients with right ventricular failure. Studies 
looking at concomitant insertion of the ProtekDuo and LVAD to preempt RVF in patients with 
impaired RV function have shown advantageous effects on patient outcomes compared to 
insertion post-LVAD (Schmack). It is expected that preemptive placement of RVADs prior to or 
during LVAD implantation to preemptively treat RVF will similarly result in improved patient 
outcomes. 
 
III. SPECIFIC AIMS 
The purpose of this study is to compare clinical outcomes of standard of care treatment versus 
preemptive percutaneous right ventricular assist device (RVAD) placement surrounding left 
ventricular assist device (LVAD) implantation. We hypothesize that the use of the RVAD will 
mitigate need for inotropic support, reducing the vasoactive-inotrope score (VIS) by 50%, and 
will improve end organ function in patients compared to standard of care. 
 
IV. SUBJECT SELECTION 
 
This trial will include both a prospective interventional cohort and a retrospective control cohort. 
The prospective interventional cohort will consist of patients undergoing LVAD implantation at 
Massachusetts General Hospital. These patients will receive an RVAD (either the ProtekDuo or 
Impella RP) prior to or during LVAD implantation. The historical control cohort will consist of 
retrospective data collection on patients who have undergone LVAD implantation in the past. 
This group will be age and sex matched with the enrolled prospective interventional patients.  
 
 
 
 
 
 

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INCLUSION: 
• Ages 18-75 
• Accepted for LVAD implantation by MGH multidisciplinary team 
 
EXCLUSION: 
• Disorders of the pulmonary artery wall that would preclude placement or correct 
positioning of RVAD 
• Presence of mechanical valves 
• Mural thrombosis of the right atrium or vena cava 
• Anatomic conditions precluding insertion of the RVAD 
• Complicated venous access precluding or complicating device placement (i.e. femoral 
and jugular thrombosis) 
• No evidence of right ventricular dysfunction by echocardiogram 
 
V. SUBJECT ENROLLMENT 
 
 
Potential study subjects will be identified only after they have been deemed eligible and 
appropriate for LVAD implantation. 
The primary specialist/healthcare provider who is known to the potential subject and has 
firsthand knowledge of the patient’s medical history will give approval for his/her patient to be 
contacted for research purposes. The primary specialist/healthcare provider will introduce the 
study and obtain the patient’s/family’s permission to be contacted by study staff verbally. 
Potential participants may be identified from among the PI’s, or Co-Investigators’ direct patient 
populations. It will be made clear to the subject that participation in the study is entirely 
voluntary and that their decision will not affect their care now or in the future.   
The Investigator will explain the research study to the potential subject in detail including the 
purpose of the research, procedures, risks and potential benefits, right to withdraw, alternative 
care and confidentiality. Subjects will be given a copy of the consent form to review to ensure 
the subject is able to understand the study. Potential subjects will be encouraged to speak with 
friends/family and/or other healthcare providers about research participation. Subjects are told 
that the PI will also be available to discuss the study. 
Once a subject decides to participate, a licensed physician investigator will obtain informed 
consent from the subject. The consent discussion between the investigator and patient participant 
will be documented in the research record. Subjects will be given a copy of their signed consent 
form. The original signed consent form will be retained in the study binder. A copy of the signed 
consent form will be filed in the subject’s medical record. Should the participant have additional 
questions, a licensed physician investigator will be offered (and made available) to discuss the 
consent questions. 

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Phone consent will be considered if a subject wishes to participate but does not want to wait until 
their next regularly scheduled appointment to sign consent.  The Investigator will assure that the 
subject has a copy of the consent form during the phone discussion.  The consent will have been 
given in person at a prior visit or in the event the subject has misplaced the consent, will be sent 
via mail, fax or email.  Emails sent outside Partners will be sent securely by encryption per 
Partners policy, unless the subject agrees to allow non-secure email transmission.  The phone 
consent discussion will reflect the same process if conducted in person.  If the subject agrees, 
he/she will sign the consent form and return it to the research nurse.  Upon receipt, the consent 
form will be signed by the Investigator who spoke with the subject by phone and a copy of the 
consent form (with both signatures) will be returned to the subject (with the original consent 
containing both signatures retained in the research file).  A note will be entered in the research 
file inclusive of the following:  consent method (i.e. by phone), who obtained consent, notation 
that all questions/concerns were answered, and the date/time consent was obtained. 
If it is determined that a potential subject is not capable to give consent or in the event of patient 
incapacity by sedation/intubation/clinical acuity, the PHRC preferred order of surrogates will be 
followed and the Investigator will document the relationship of the surrogate to the subject in the 
research record: 
a. Court appointed guardian with specific authority to consent to participation in 
research or authority to make health care decisions for a class of diagnostic and 
therapeutic decisions inclusive of the proposed research; 
b. Health care proxy/person with durable power of attorney with specific authority for 
making health care decisions inclusive of the proposed research; or 
c. Spouse, adult child, or other close family member who knows the subject well and 
has been involved in their care. 
 
A physician Investigator will approach the surrogate using the same process as outlined in 
obtaining consent for all subjects. The study will be explained in full to the surrogate, including 
the purpose of the research, procedures, risks and benefits, right to withdraw, alternative care and 
confidentiality. We will ensure and document that the surrogate understands that his/her 
decisions should be based on substituted judgment. If a potential subject did not previously 
express a view, the surrogate should make the decision based on the potential subject’s best 
interests. We will explain the difference between standard of care and research. 
If surrogate consent is obtained, the basis of the determination of the subject’s lack of capacity 
will be documented in the research records, along with a description of the relationship of the 
surrogate. 
After consent is signed, subjects in the prospective interventional cohort will be assigned to 
receive either the Impella RP or ProtekDuo, as indicated by the treating physician. The RVAD 
will be placed within 48 hours preoperatively of the LVAD implantation, at the time of LVAD 
implant, or immediately following the implant. The RVAD will be left for up to 72 hours. 
RVAD management will be performed according to MGH standard of care by the medical staff. 

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There will be no consent process for the historical control cohort as there are no interventions for 
this group. The clinical data required for this study is already collected in a secure database per 
standard of care. 
 
VI. STUDY PROCEDURES 
 
All LVAD candidates at Massachusetts General Hospital (MGH) will be screened for trial 
eligibility. Every eligible candidate will be asked to participate. Subjects who consent to the 
study will undergo pre-operative or intra-operative placement of an RVAD, which will be left in 
up to 72 hours postoperatively. If it is determined that a subject requires support for longer than 
72 hours, the treating physician will consider utilizing a more durable form of right ventricular 
support (CentriMag paracorporeal RVAD requiring direct cannulation), as is standard practice. 
The type of RVAD (Impella RP or ProtekDuo) inserted will be determined by patient needs and 
venous access and will be up to the discretion of the treating physician. The use of the ProtekDuo 
will be prioritized due to the benefit of the jugular approach in device placement, which does not 
limit patient mobility. If there is no jugular access, the Impella RP, which is placed through a 
femoral approach, will be used. We aim to enroll 25 subjects in the prospective interventional 
cohort, and compare to 25 subjects in the matched retrospective control cohort.  
All enrolled patients in the prospective interventional cohort will undergo surgical placement of 
a percutaneous RVAD within 48 hours preoperatively to LVAD implantation, at the time of 
LVAD implant, or immediately following the implant. After removal of the RVAD, subjects will 
receive standard treatment according to MGH’s standard of care. Data will be obtained for 
subjects in both cohorts from the electronic medical record in EPIC at MGH and will be 
reviewed throughout the study through the 1-year follow-up period. Other standard of care tests 
are administered regularly at LVAD follow-up visits, including: the KCCQ-12 and EQ-5D 
surveys, a neurocognitive trailmaking test, and a six-minute walk and gait speed test. These are 
collected per standard of care at the following timepoints: pre-implant, 3 month (+/- 30 days), 6 
month (+/- 60 days), and 1 year (+/- 60 days). These results will also be collected and entered to 
the study database. 
Clinical data will be collected and entered into the secure database by study coordinators. All 
subjects will be followed through 12-month post-LVAD implantation with data collection 
occurring at the following timepoints: pre-implant, time of implant, discharge, 1 week (+/- 3 
days), 1 month (+/- 7 days), 3 month (+/- 30 days), 6 month (+/- 60 days), and 1 year (+/- 60 
days), all of which will align with routine clinical standard of care visits. Subjects will not be 
asked to come for additional visits separate from their usual standard of care visits. All follow-up 
tests and procedures will also be done per standard of care. 

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VII. DATA COLLECTION SCHEDULE 
 
DATA COLLECTION SCHEDULE 
  
  
  
  
  
  
  
  
  
ASSESSMENT  
Pre-LVAD  
Implant 
RVAD  
Placement 
LVAD  
Implant 
1 Week 
Follow-
up 
Implant  
Discharge 
1 Month  
Follow-up 
3 Month  
Follow-
up 
6 Month  
Follow-up 
1 Year  
Follow-up 
Screening 
X 
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
RVAD Placement Details 
  
X 
 X 
  
  
  
  
  
  
LVAD Implant Details 
  
  
X 
  
  
  
  
  
  
Discharge Details 
  
  
  
  
X 
  
  
  
  
Status 
X 
  
  
X 
  
X 
X 
X 
X 
Right Heart Failure 
Assessment 
  
  
  
X 
  
X 
X 
X 
X 
Hemodynamics 
X 
  
  
X 
  
X 
X 
X 
X 
Medications 
X 
  
  
X 
X 
X 
X 
X 
X 
Laboratory  
X 
  
  
X 
  
X 
X 
X 
X 
Device Details 
  
  
  
  
  
  
X 
X 
X 
Exercise/Trailmaking 
X 
  
  
  
  
  
X 
X 
X 
Quality of Life 
X 
  
  
  
  
  
X 
X 
X 
Adverse Events 
  
X 
X 
X 
  
X 
X 
X 
X 

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VIII. BIOSTATISTICAL ANALYSIS 
 
STUDY VARIABLES 
Eligibility Data 
Potential study participants who have left-heart failure and are planned to undergo LVAD 
placement will be approached by the study staff. The study will be explained, and these potential 
participants will be provided with study information and consent forms. Potential participants who 
meet study criteria will be assigned a unique identifier at this time (regardless if they are enrolled, 
which will ensure accurate recording of number of screened vs. enrolled patients). Enrolled 
subjects in the prospective arm will be matched to historical controls, which will consist of patients 
who underwent LVAD implantation in the past in the absence of pre-operative or concurrent 
percutaneous RVAD placement. 
 
Demographics – collected at outpatient visit when patient is being considered for LVAD placement  
Demographic data assessed and recorded at the initial screening visit will include date of birth, 
gender, race, and ethnicity.  
 
Comorbidities 
Past medical history will be assessed at the time of screening and documented at the time of 
enrollment. Data collected will relate to underlying cardiovascular pathology and to associated 
pathology of the pulmonary, renal, hepatic, endocrine, hematologic, or neurologic systems.  
 
Medications 
Data on both active and past medications will be collected at the time of initial screening. If the 
patient is admitted at the time of screening, both current inpatient medications and home 
medications will be recorded. If the patient is outpatient at the time of screening, home medications 
will be recorded. Record of active medications will also be collected at each timepoint throughout 
the study. 
 
Laboratory Data 
Pre- and post-operative lab data including but not limited to CBC, CMP, INR, NT-pro-BNP will 
be collected at various timepoints during the study, including at time of enrollment.  
 
EKG, ECHO, and Cardiac Catheterization assessment 
EKG, ECHO, and Cardiac Catheterization results will be collected at several points during the 
study.  
 
Inpatient Events/Procedures  
Data on events and procedures that occur while patients are admitted will be collected on an 
ongoing basis while study participants are admitted to the hospital. Where complications occur, 
adverse event forms will be completed and principal investigators will be notified.  

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PRIMARY ENDPOINT 
The primary outcome of the study will the vasoactive inotropic score (VIS). Both the average/mean 
VIS and the cumulative VIS over the first 24 hours post-LVAD implantation of the experimental 
cohort (those enrolled in the prospective study who undergo pre-emptive RVAD placement) will 
be compared to a historical cohort of patients who received the current standard of care. The VIS 
will be calculated for each patient in both arms of the study. Both the maximum score and the 
cumulative sum achieved in the first 24 hours after LVAD implantation will be recorded (maximal 
24-hour VIS and cumulative 24-hour VIS).  
The primary analysis will be performed in an intention-to-treat fashion using a two-sided T-test 
(alpha level=0.05). The null hypothesis is that the mean maximal 24-hour VIS will not differ 
between intervention and historical groups. The alternate hypothesis is that compared to standard 
of care (historical cohort), placement of an RVAD within 48 hours before or during LVAD 
implantation will decrease the mean maximal 24-hour VIS score by 50%. Analysis assumptions 
will include independence of study groups and lognormal (or normal) distribution of data in each 
group.   
 
SECONDARY OUTCOMES 
Secondary end points will include: 
- Total VIS (throughout hospitalization) 
- ICU length of stay (LOS) 
- Total post-operative LOS after LVAD implantation 
- Survival at discharge after LVAD placement  
- Survival at 1 year after LVAD placement or heart transplant  
- End organ dysfunction including 
o Development of acute kidney injury (AKI) – defined as increase in serum 
creatinine (sCr) to 4mg/dl or greater, a 150% or greater increase in sCr over 
the baseline preoperative value, or a new requirement for renal replacement 
therapy 
o Liver dysfunction 
- LVAD device speed 
 
Cox proportional hazard models (one sided, 0.05 significance level) will be used to compare 
rates of secondary outcomes between intervention and historical arms. Event rates and relative 
risks will also be estimated for each of these outcomes. 
 
 
POWER ANALYSIS 
Sample size calculations are estimated based on expected effect size, which was determined 
based on expert consensus (reduction in the mean maximal 24-hour VIS score by 50% in the 
intervention arm compared to the historical controls). 80% power will be generated with 2-tailed 
confidence interval of 0.05 from a sample size of 34 patients (17 per group). Estimating a 

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standard deviation of 0.5 of the outcome in the population and 20% attrition and/or cross-over, 
investigators anticipate that 20 patients will be needed to test this hypothesis. This power 
estimation assumes a lognormal distribution of the data. We plan to allow for 25 patients to 
participate in the prospective arm of the study to allow for incorrect assumptions. 
 
 
IX. RISKS AND DISCOMFORTS 
 
There is a risk of complications associated with the surgical procedure of Impella RP or 
ProtekDuo placement, which may include arrhythmia, atrial fibrillation, bleeding, cardiac 
tamponade, cardiogenic shock, death, device malfunction, hemolysis, hepatic failure, insertion 
site infection, perforation, deep venous thrombosis, pulmonary valve insufficiency, respiratory 
dysfunction, sepsis, thrombocytopenia, thrombotic vascular complication, tricuspid valve injury, 
vascular injury, venous thrombosis, ventricular fibrillation and/or tachycardia. 
The risk to privacy is a minimal risk and obtaining data will not affect the rights or welfare of 
subjects. All pertinent information regarding the subjects in this study is documented within the 
electronic medical record in EPIC. Clinical data for this study will be collected from EPIC by 
IRB-approved researchers listed on the protocol. Only authorized personnel will have access to 
identifiable data. The electronic data will be stored in a password protected fashion on an internal 
secure server, accessible only through a Partners encrypted device with anti-virus software. Data 
will be stored via a secure Electronic Data Collection (EDC) site. Paper-based data will be stored 
in a locked and secure office. Neither identifiable nor non-identifiable data will be sent outside 
Partners or to Partners researchers not listed on the protocol. Data will be used only for clinical 
outcome research. Patient identifiers will be removed from the data and destroyed after all data 
has been collected, the study has been completed, or all regulatory obligations have been met. 
Only de-identified datasets will be retained after this point. 
 
X. POTENTIAL BENEFITS 
 
Previous studies have shown that RVAD placement post-LVAD implantation improved 
hemodynamics, including an increase in cardiac index and decrease in central venous pressure. 
These patients also experienced reversal of shock, favorable survival, and improved LVAD flow. 
RVADs also mitigate the need for inotropes, and thereby lessen inotrope-related adverse 
outcomes such as worsening biomarkers of end organ function. We hypothesize that preemptive 
RVAD placement could lead to a lower vasoactive inotrope score, better clinical outcomes, 
shortened hospital length of stay, and improved end-organ function in patients with LVADs. 
Therefore, subjects may receive direct benefits from their participation in this study. This study 
may also benefit future LVAD patients by potentially improving standard of care procedures 
surrounding LVAD management. 

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XI. MONITORING AND QUALITY ASSURANCE 
 
During the course of the trial, the PI will oversee the conduct of the trial and will review study 
documents for completeness and accuracy as well as compliance with the study protocol and 
applicable regulations. The PI is ultimately responsible for protecting the safety and welfare of 
all subjects.   
 
The PI is responsible for reviewing all laboratory, imaging and procedural reports for clinical 
significance. It is the PI’s responsibility to determine if any reports are significant or meet the 
guidelines for adverse event and/or serious adverse event reporting for both the sponsor and the 
IRB. 
 
Safety data will be continuously monitored and reviewed in order to quickly identify any 
unforeseen risks to subjects. The physician investigator will perform regular, internal reviews of 
all adverse events. Events will be reported to the IRB per the outlined requirements and a 
summary of the safety data will be sent the IRB at the time of the annual renewal. Unanticipated 
problems involving risks to subjects or others including adverse events will be reported to the 
PHRC in accordance with PHRC unanticipated problems reporting guidelines. 
 
All serious adverse events (SAEs) will be assessed by the principal investigator, documented and 
reported to the IRB according to PHRC guidelines. AEs that are not serious but that are notable 
and could involve risks to subjects will be summarized in narrative or other format and submitted 
to the IRB at the time of continuing review. 
 
We will perform an interim safety/outcomes analysis after the first 10 subjects have been 
enrolled to ensure that the anticipated risk/benefit assessment remains unchanged. The report 
will be made available to the IRB in a timely manner. If this analysis shows that 10 subjects 
provide enough data to draw significant conclusions, enrollment will be stopped and the study 
will be concluded. If other assumptions prove to be wrong and additional patients will be needed, 
this will be carefully considered and communicated to the IRB prior to proceeding.  
 
 
 
 
 
 
 

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XII. REFERENCES 
 
1. Anderson, M., Morris, D. L., et. Al. (2018). Outcomes of patients with right ventricular failure 
with the Impella RP device. The Journal of Heart and Lung Transplantation, 37(12), 1448-1458. 
doi: 10.1016/j.healun.2018.08. 
2. Han, J., Pinsino, A., et. Al. (2019). Prognostic value of vasoactive-inotrope score following 
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