Assessing the Hemostatic Efficacy of Pathogen Reduced Platelets in Children Undergoing Cardiopulmonary Bypass Surgery: A Pilot Clinical Trial
Phase: PHASE4
Conditions: Cardiopulmonary Bypass Surgery
Sponsor: Weill Medical College of Cornell University

TITLE: Assessing the HemostaƟc Eﬃcacy of Pathogen Reduced Platelets in Children Undergoing 
Cardiopulmonary Bypass Surgery: A Pilot Clinical Trial 
Date: 31-Dec-2023 
NCT #: NCT05293106 

 
 
  
Page # i 
 
 
TITLE: Assessing the Hemostatic Efficacy of Pathogen Reduced Platelets in Children 
Undergoing Cardiopulmonary Bypass Surgery: A Pilot Clinical Trial  
 
IRB Protocol #: 21-11024115 
IND/IDE #: Not applicable 
 
Version Date: 12/31/23 
Funding Source(s): Department of Pediatrics, Weill Cornell, Collective Power Grant 
 
Principal Investigator: 
 
Marianne Nellis, MD, MS 
525 East 68th St, M512, New York, NY 10065 
(212) 746-3056 
Man9026@med.cornell.edu 
 
 
Co-Investigators: 
 
Sophia Hsien, MD 
 
 
Fellow in Pediatric Cardiology 
 
 
Soh9031@med.nyp.org 
 
 
 
 
 
 
Liliko Chung 
 
 
Clinical Data Coordinator, PICU 
 
 
lhc4027@med.cornell.edu 
 
 
 
Margaret Cormack 
 
 
Regulatory Coordinator 
 
 
Mac4035@med.cornell.edu 
 
 
 
Robert Desimone, MD 
 
 
Chief Transfusion Medicine Services 
 
 
Rod9096@med.cornell.edu 
 
 
 
Pranesh Rajendran 
 
 
Transfusion Medicine Research Coordinator 
 
 
Prr4005@med.cornell.edu 
 
 
 
Statisticians: 
Charlene Thomas, MS, cht2028@med.cornell.edu 
Linda Gerber, PhD, lig2002@med.cornell.edu  
 
 
Medical Monitor: 
Weill Cornell Medicine DSMB 
 
 
 
Participating Sites:  Komansky Children's Hospital at Weill Cornell (PI – Marianne Nellis, 
man9026@med.cornell.edu), Morgan Stanley Children's Hospital (PI – Brett Anderson, 
bra2113@cumc.columbia.edu) 
 
 

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Table of Contents 
CONFIDENTIALITY STATEMENT ................................................................................... VI 
LIST OF ABBREVIATIONS.............................................................................................. VII 
1. PROTOCOL SUMMARY ................................................................................................ 1 
1.1 
Schema .................................................................................................................... 3 
1.2 
Study Objectives and End Points ........................................................................ 4 
1.2.1  Primary Objectives ......................................................................................... 4 
To determine the amount of post-operative bleeding in children receiving PR 
versus LVDS platelet transfusions during and following cardiopulmonary bypass 
surgery. ............................................................................................................................. 4 
1.2.2  Secondary Objectives .................................................................................... 4 
1.2.3  Exploratory Objectives ................................................................................... 4 
1.2.4 
Primary Endpoints .......................................................................................... 4 
1.2.5 
Secondary Endpoints ..................................................................................... 4 
2. BACKGROUND .............................................................................................................. 4 
2.1 
Disease .................................................................................................................... 4 
2.2 
Investigational Agent/Device, or Surgical Treatment/Method ......................... 4 
2.3 
Rationale ................................................................................................................. 5 
Given the lack of evidence of hemostatic efficacy of PR platelets in children, we 
are seeking to characterize the hemostatic efficacy of PR platelets by comparing 
post-operative bleeding in children undergoing CPB who receive PR versus 
LVDS platelet transfusions. ............................................................................................ 5 
2.4 
 Risk/Benefit Assessment..................................................................................... 5 
2.4.1 
Known Potential Risks ................................................................................... 5 
2.4.2 
Known Potential Benefits .............................................................................. 6 
2.4.3 
Assessment of Potential Risks and Benefits .............................................. 6 
2.5 
Correlative Studies Background ......................................................................... 6 
3. STUDY DESIGN.............................................................................................................. 6 
3.1 
Overall Design ........................................................................................................ 6 
3.2 
Scientific Rationale for Study Design ................................................................. 7 
3.3 
Justification for Dose ............................................................................................ 7 
3.4 
End of Study Definition ......................................................................................... 7 
4. SUBJECT SELECTION .................................................................................................. 7 
4.1 
Study Population ................................................................................................... 7 
4.2 
Inclusion Criteria .................................................................................................... 7 
4.3 
Exclusion Criteria .................................................................................................. 8 
4.4 
Lifestyle Considerations ....................................................................................... 8 
4.5 
Screen Failures ...................................................................................................... 8 

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4.6 
Strategies for Recruitment and Retention .......................................................... 8 
5. REGISTRATION PROCEDURES .................................................................................. 9 
5.1 
Subject Registration (WCM only) ........................................................................ 9 
5.2 Subject Registration (Sub-sites) ............................................................................. 9 
6. STUDY PROCEDURES .................................................................................................. 9 
6.1 
Schedule of Assessments .................................................................................... 9 
6.1.1 
Screening Visit .............................................................................................. 10 
6.1.2 
Treatment Phase ........................................................................................... 10 
6.1.2.1 
Operative Course ....................................................................................... 10 
6.1.2.2 
Post-Op Days 0-2 ....................................................................................... 11 
6.1.3 
Follow-up Phase ............................................................................................ 11 
7. STUDY INTERVENTION .............................................................................................. 11 
7.1 
Study Intervention/Device Description ............................................................. 11 
7.2 
Availability ............................................................................................................ 11 
7.3 
Acquisition and Accountability.......................................................................... 11 
7.4 
Formulation, Appearance, Packaging, and Labeling ...................................... 12 
7.5 
Product Storage and Stability ............................................................................ 12 
The blood products will be stored as per normal protocol in the blood banks at 
each site. ......................................................................................................................... 12 
7.6 
Preparation ........................................................................................................... 12 
7.7 
Dosing and Administration ................................................................................ 12 
Platelets will be prescribed and administered at the discretion of the clinical 
teams. Each platelet transfusion will be dosed as 10mL/kg as per standard of 
care. ............................................................................................................................. 12 
7.7.1 
Dosing Delays/Dose Modifications ............................................................. 12 
7.8 
General Concomitant Medication and Supportive Care Guidelines ............. 12 
7.9 
Duration of Therapy and Criteria for Removal from Study ............................ 12 
7.10  Duration of Follow Up .......................................................................................... 12 
7.11 Measures to Minimize Bias: Randomization and Blinding .............................. 13 
7.12 Study Intervention/Follow-up Compliance ........................................................ 13 
8. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .............................................................................. 13 
8.1 
Discontinuation of Study Intervention .............................................................. 13 
8.2 
Participant Discontinuation/Withdrawal from the Study ................................ 14 
8.3 
Lost to Follow Up ................................................................................................. 14 
9. CORRELATIVE/SPECIAL STUDIES ........................................................................... 14 
Not applicable ............................................................................................................. 14 
9.1 
Laboratory Correlative Studies .......................................................................... 14 
Not applicable ............................................................................................................. 14 

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9.2 
Special Studies .................................................................................................... 14 
Not applicable ............................................................................................................. 14 
10.  MEASUREMENT OF EFFECT .................................................................................. 14 
10.1 Response Criteria .................................................................................................. 14 
10.2 Duration of Response ........................................................................................... 15 
10.3 Progression-Free Survival ................................................................................... 15 
10.4 Other Response Parameters ................................................................................ 15 
11. DATA REPORTING / REGULATORY CONSIDERATIONS .................................... 15 
11.1 Data Collection....................................................................................................... 15 
11.1.1 REDCap ............................................................................................................ 15 
11.2 Regulatory Considerations .................................................................................. 15 
11.2.1 Institutional Review Board/Ethics Committee Approval ........................... 15 
11.2.2 Ethical Conduct of the Study ........................................................................ 16 
11.2.3 Informed Consent ........................................................................................... 16 
11.2.4 Compliance with Trial Registration and Results Posting Requirements 17 
11.2.5 Record Retention ............................................................................................ 17 
12. STATISTICAL CONSIDERATIONS ........................................................................... 17 
12.1 Study Design/Endpoints ....................................................................................... 18 
12.2 Sample Size/Accrual Rate .................................................................................... 18 
12.3 Stratification Factors ............................................................................................ 19 
12.4 Analysis of Endpoints ........................................................................................... 19 
12.4.1 Analysis of Primary Endpoints ......................................................................... 19 
12.4.2 Analysis of Secondary Endpoints.................................................................... 19 
12.5 Interim Analysis ..................................................................................................... 19 
THE DSMB WILL CONDUCT REGULAR REVIEWS REGARDING THE EFFICACY OR 
FUTILITY OF THE TREATMENT. NO FORMAL STOPPING RULES HAVE BEEN 
PLACED FOR THIS PROTOCOL. ................................................................................... 19 
12.6 Reporting and Exclusions .................................................................................... 19 
12.6.1 
Evaluation of Toxicity ............................................................................... 19 
12.6.2 
Evaluation of Response ............................................................................ 19 
13. ADVERSE EVENT REPORTING REQUIREMENTS ................................................ 20 
13.1 Adverse Event Definition ...................................................................................... 20 
13.1.1 
Investigational Agent or Device Risks (Expected Adverse Events) ... 20 
13.1.2 
Adverse Event Characteristics and Related Attributions .................... 20 
13.1.3 
Recording of Adverse Events .................................................................. 20 
13.1.4 
Reporting of AE to WCM IRB ................................................................... 20 
13.1.5 
Reporting Events to Participants ............................................................ 20 
13.1.6 
Events of Special Interest ......................................................................... 21 
13.1.7 
Reporting of Pregnancy ............................................................................ 21 

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13.2 Definition of SAE ................................................................................................... 21 
13.2.1 
Reporting of SAE to IRB ........................................................................... 21 
13.2.2 
Reporting of SAE to FDA .......................................................................... 21 
Not applicable ................................................................................................................ 21 
13.3 AE/SAE Follow Up ................................................................................................. 21 
13.4 Time Period and Frequency for Event Assessment and Follow Up ............... 21 
14. UNANTICIPATED PROBLEMS INVOLVING RISKS TO SUBJECTS OR OTHERS22 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others 
(UPIRTSO) ....................................................................................................................... 22 
14.1.2 
Unanticipated Problem Reporting ........................................................... 22 
15. DATA AND SAFETY MONITORING PLAN (DSMP) ................................................ 23 
16. REFERENCES ............................................................................................................ 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Statement of Compliance 
 
The trial will be conducted in accordance with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP), applicable United States (US) Code of Federal 
Regulations (CFR). The Principal Investigator will assure that no deviation from, or 
changes to the protocol will take place without prior agreement from all investigators and 
documented approval from the Institutional Review Board (IRB), except where necessary 
to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the 
conduct of this study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the IRB for review and approval.  Approval of both the protocol and 
the consent form must be obtained before any participant is enrolled.  Any amendment to 
the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  All changes to the consent form will be IRB approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 
Confidentiality Statement 
 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or 
institutional review boards. The contents of this document shall not be disclosed to others without 
written authorization from WCM, unless disclosure on ClinicalTrials.gov is federally required. 
 
 
 
 
 
_________________________________________________________________ 
Institution Name 
 
 
 
 
 
 
______________________________       _____________________________     ____________ 
Principal Investigator’s Name                 Principal Investigator’s Signature     Date  
 
 
 
 
 
 
 
 
 
 

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List of Abbreviations 
 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTSC 
Clinical Translational Science Center  
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRBFA 
Human Research Billing Analysis Form 
HUD 
Humanitarian Use Device  
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption  
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
UIRTSO 
Unanticipated Problem Involving Risks to Subjects or Others 
WCM 
Weill Cornell Medicine 

Protocol # 21-11024115 
Version Date 5Aug2022 
 
  
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1. Protocol Summary 
 
Full Title:  
 
 
 
Assessing the Hemostatic Efficacy of Pathogen Reduced Platelets 
in Children Undergoing Cardiopulmonary Bypass Surgery: A Pilot 
Clinical Trial 
Short Title: 
 
 
 
Hemostatic Efficacy of Pathogen Reduced Platelets 
Clinical Phase: 
 
 
IV 
Principal Investigator:  
Marianne Nellis, MD, MS 
Study Description:   
This is a pilot clinical trial to assess the post-operative bleeding in 
children who receive pathogen-reduced (PR) platelet transfusions 
versus standard (large volume delayed sampling – LVDS) platelet 
transfusions both during and for 24 hours following. 
cardiopulmonary bypass surgery. 
Sample Size: 
 
126 (63 per group) 
Enrollment: 
 
This study will enroll approximately 252 subjects and screen up to 
500 subjects. Though the sample size is 126, since the decision to 
transfuse platelets is at the discretion of the clinical team, and our 
preliminary data shows approximately 50% of children are 
transfused, we will need to enroll double the sample size, or 252 
children (see full protocol for further explanation). 
Study Population: 
 
Children (ages 0-18 years of age) undergoing cardiopulmonary 
bypass surgery 
Enrollment Period:  
Length of hospitalization 
Study Design: 
 
This is an open label, randomized clinical trial of children 
undergoing cardiopulmonary bypass surgery at either Komansky 
Children's Hospital/Weill Cornell or Morgan Stanley Children's 
Hospital/Columbia. For children who require platelet transfusions 
either intra or post-operatively for the first 24 hours (decision to 
transfuse left at discretion of clinical team), they will receive either 
all PR or all LVDS platelet transfusions. Bleeding from the 
surgically placed chest tube will be recorded per hour for the first 
24 hours post-operatively. In addition, the total volume of 
transfusion of any blood products will be recorded.  
Description of Sites/  
Facilities Enrolling 
Participants: 
 
Komansky Children's Hospital/Weill Cornell and Morgan Stanley 
Children's Hospital/Columbia.   
 
Study Duration: 
 
6/30/2024 
Participant Duration: 
Length of hospitalization (no follow-up visits necessary) 
Study Agent/Device Name  
Intervention Description: 
Both PR and LVDS platelets are considered standard of care 
(currently whatever product is available is dispensed by 
transfusion medicine services). Platelets will be transfused in 
doses of 10mL/kg. 

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Primary Objective: 
To determine the amount of post-operative bleeding in children 
receiving PR versus LVDS platelet transfusions during and 
following cardiopulmonary bypass surgery  
 
Secondary Objectives: 
To determine the blood product requirements and nosocomial 
infections in children receiving PR versus LVDS platelet 
transfusions during and following cardiopulmonary bypass surgery 
 
Primary Endpoints: 
Chest tube output for first 24 hours following cardiopulmonary 
bypass surgery  
 
Secondary Endpoints: 
Total dose red blood cell transfusions in first 48 hours, Total blood 
products transfused (intra and post-operatively) in first 48 hours, 
nosocomial infections  
 

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1.1 Schema 
 
 
Prior to 
Enrollment 
 
 
 
 
 
 
 
  
 
 
 
Time Point: 
Intra-op 
 
 
 
 
 
 
Time Point: 
Post-op 
Frist 24 hours 
 
 
 
 
 
 
 
 
Time Point: 
Hospital discharge 
 
 
 
Total N:  Obtain informed consent. Screen potential participants by inclusion and 
exclusion criteria; obtain history, document. 
Administer initial study intervention (need for transfusion determined by clinical team). 
Record: Surgical repair, RACHS and STS scores (validated surgical complexity), 
cardiopulmonary bypass time, cross clamp time, hypothermic circulatory arrest time, 
use of antifibrinolytics, blood products required  
Record: Mechanical ventilation free days,  
Vasoactive free days, PICU free days, 
nosocomial infections, mortality 
Arm 2 – LVDS 
platelets 
63 participants 
Arm 1 – PR platelets 
63 participants 
Repeat study intervention (need for transfusion determined by clinical team). 
Record: chest tube output, blood products required 
Randomize 

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1.2 Study Objectives and End Points 
 
 
1.2.1  Primary Objectives  
 
To determine the amount of post-operative bleeding in children receiving PR versus 
LVDS platelet transfusions during and following cardiopulmonary bypass surgery. 
 
1.2.2  Secondary Objectives  
 
To determine the blood product requirements and nosocomial infections in children 
receiving PR versus LVDS platelet transfusions during and following cardiopulmonary 
bypass surgery. 
 
1.2.3  Exploratory Objectives 
 
 
 
 
Not applicable 
 
1.2.4 Primary Endpoints 
 
 
Chest tube output for first 24 hours following cardiopulmonary bypass surgery 
 
1.2.5 Secondary Endpoints 
 
Total dose red blood cell transfusions in first 48 hours, total blood products transfused 
(intra and post-operatively) in first 48 hours, nosocomial infections 
 
 
2. Background 
 
2.1 Disease 
 
Pediatric patients undergoing cardiopulmonary bypass (CPB) are at high risk of ongoing 
bleeding due to hemodilution, platelet dysfunction, hypothermia and anti-coagulation [1]. 
Therefore, they often require post-operative hemostatic blood component transfusions, most 
commonly platelet transfusions, in order to prevent to stop bleeding [2, 3]. These children 
represent a unique patient population in that they each have mediastinal and/or pleural 
drains placed intra-operatively and therefore, their post-operative bleeding is quantifiable. 
 
2.2 Investigational Agent/Device, or Surgical Treatment/Method 
 
Platelet transfusions are frequently prescribed to children to prevent or treat bleeding, but 
have been associated with increased transfusion reactions, as compared to their adult 
counterparts [4], as well as increased mortality [5]. Though red blood cells (RBCs) and 
plasma must be stored at lower temperatures, platelets are traditionally stored at room 
temperature with gentle agitation. Such conditions incur the additional risk of microbial 
contamination [6, 7]. To combat this, pathogen-reduced (PR) platelets, treated with either 
riboflavin or amotosalen and then exposed to ultraviolet illumination, have been developed 
[8, 9]. Studies have demonstrated that PR technology inactivates infectious agents [10] and 
lymphocytes [11]. In adult patients, PR platelets have been linked to increased platelet 
refractoriness and decreased platelet correct count increments, but no clinically significant 

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bleeding or increased risk of serious adverse events [12, 13]. 
 
Similar studies in the pediatric population have been limited. In an observational study of 
cohort of 240 neonates and children, patients who received PR platelets had an overall 
increase in total transfusion need as compared to those receiving non-PR platelets [14]. In a 
smaller cohort of children with oncologic diagnoses, those who received PR platelets had 
lower incremental increases in their platelet count following transfusion, but no significant 
increase in bleeding events [15]. The hemostatic efficacy of PR platelets has not been 
sufficiently examined in pediatric patients, particularly in those with ongoing bleeding. 
 
Given the increased safety of PR platelets in regard to transfusion transmitted infections, the 
FDA encouraged all transfusion medicine services to provide either PR platelets or LVDS 
platelets to all patients in guidance issued in 2017. The transfusion medicine services at 
New York Presbyterian Hospital (on both the Weill Cornell and Columbia campuses) began 
introduction of PR platelets into the inventory in 2017 and maintain an inventory of both PR 
platelets and LVDS platelets currently. There is no difference in the risk of infection between 
PR and LVDS platelet products. 
 
 
2.3 Rationale 
 
Given the lack of evidence of hemostatic efficacy of PR platelets in children, we are seeking 
to characterize the hemostatic efficacy of PR platelets by comparing post-operative bleeding 
in children undergoing CPB who receive PR versus LVDS platelet transfusions. 
 
2.4  Risk/Benefit Assessment  
 
 
 
2.4.1 Known Potential Risks 
 
The need for the transfusion of any blood component, including platelet transfusions, will 
be at the discretion of the clinical team. Therefore, this study will not put an individual 
subject at increased risk of receiving a transfusion. In addition, if the platelet product to 
which the patient is assigned is not available, the patient will receive the available 
product without delay. Therefore participation in the study does not place the subject at 
risk of delayed transfusion. 
 
The transfusion of any blood component carries the risk of transfusion transmitted 
infections, allergic reactions, transfusion associated acute lung injury, transfusion 
associated circulatory overload and transfusion related immunomodulation. However, 
these risks are known for both PR and LVDS products so that participation in the study, 
in which the subject will be randomized to either all PR or all LVDS platelet transfusions 
during cardiopulmonary bypass surgery and following for 24 hours, poses no increased 
risk as compared to not participating in the study. 
 
PR platelets have been associated with a lower incremental rise in platelet count 
following a transfusion as compared to LVDS platelets in children with cancer. 
Therefore, subjects in this study are at risk of having a lower incremental rise in their 
platelet count if they receive PR platelets as compared to LVDS platelets. However, 
since platelets are transfused in the cardiac population not because of thrombocytopenia 

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but rather platelet dysfunction, this difference in platelet count should not affect the 
subjects’ risk of bleeding. 
 
It is unknown if either product (PR or LVDS platelet transfusions) is less efficacious in 
hemostasis, i.e. if one product leads to less bleeding. 
 
De-identified clinical information (demographics, surgical characteristics, details 
regarding the platelet transfusion and clinical outcomes) will be collected on each 
subject. Though de-identified, there remains a risk of loss of confidentiality.  
 
2.4.2 Known Potential Benefits  
 
Both the FDA and the transfusion medicine services at Weill Cornell and Columbia 
Universities have determined that both PR platelets and LVDS platelets are equal in 
potential benefit of decreased transfusion transmitted infections.  
 
Though it is unknown if one product is associated with improved hemostasis, if one 
product is, the subjects have the potential benefit of decreased bleeding. 
 
2.4.3 Assessment of Potential Risks and Benefits 
 
Given the minimal risks associated with this study (since the transfusions would be given 
regardless of participation in the study, the study is only ensuring a patient receives all 
PR or all LVDS platelets), the benefits of possible improved hemostasis, as well as the 
benefit to society, facilitating a greater understanding of the hemostatic efficacy, 
outweigh the risks. 
 
2.5 Correlative Studies Background 
 
 
 
Not applicable 
 
3. Study Design 
 
3.1 Overall Design 
 
This is a multisite, open-label, randomized trial of PR versus LVDS platelet transfusions 
in children undergoing cardiopulmonary bypass surgery. The study will be conducted at 
at Komansky Children’s Hospital at Weill Cornell and Morgan Stanley Children’s Hospital 
at Columbia. Given that both products are FDA approved and already used in this 
patient population, it is a Phase IV study. Based on our preliminary retrospective data, 
we hypothesize that both products will have equivalent hemostasis, as measured by 
chest tube output in the first 24 hours, as well as total blood component requirements. 
Given the complexity of surgery is associated with bleeding risk, the two groups will be 
stratified on a validated score of surgical complexity (STS scoring). All subjects will be 
enrolled in the study for the length of their hospitalization. 
 
The need for platelet transfusion will not be dictated by the study intervention, but rather 
the clinical team (both in the operating room and post-operatively, in the pediatric 
intensive care unit). Given that we do not want to delay the release of blood products 
from the blood bank, but rather have them available as standard of care in the operating 

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room, we cannot randomize the subjects at the time of the decision to transfuse 
platelets. Therefore, we will randomize subjects before the day of surgery. We recognize 
that there will be a significant number of randomized subjects (approximately 50%) who 
do not receive a platelet transfusion. Data will be collected on this group and analyzed 
both separately, and in an intention to treat model. 
 
All platelet transfusions will be given as 10mL/kg as is considered standard of care. 
 
Given the need to cross-check any transfusion of the blood component for patient safety, 
no area of the labeling will be disturbed and therefore the clinicians caring for the 
patients will be unblinded. Those responsible for data entry and data analysis will be 
blinded to the assigned groups of the subjects. 
 
To minimize bias, we will perform subgroup analyses of neonates versus all other 
children given that the neonatal coagulation system is still under development and 
different than the coagulation system of the older child. 
 
3.2 Scientific Rationale for Study Design 
 
Limited data exists regarding the hemostatic efficacy of PR platelets in children. Our 
preliminary data, a retrospective study of 140 children undergoing cardiopulmonary 
bypass surgery, suggests that PR platelets are equally efficacious in terms of post-
operative bleeding, as compared to non-PR platelets. However, retrospective studies are 
limited, and prospective randomized studies are needed to truly assess the primary 
outcome (the hemostatic efficacy).  
  
3.3 Justification for Dose  
 
Not applicable (the transfusions will be dosed equally as 10mL/kg as per standard of 
care) 
 
3.4 End of Study Definition 
 
A participant is considered to have completed the study if he or she has been 
discharged from the hospital.  
 
4. Subject Selection 
 
4.1 Study Population 
 
Children undergoing cardiopulmonary bypass surgery who meet the inclusion and exclusion 
criteria will be eligible for participation in this study.   
 
4.2 Inclusion Criteria 
 
 
1. Male or female 0-18 years of age 
 
2. Undergoing elective cardiopulmonary bypass surgery 
 
3.   Are planned to have a chest tube placed in the operating room prior to chest closure 
 

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4.3 Exclusion Criteria  
 
 
 
1.   > 18 years of age 
2.   Preterm infants (less than 38-week gestational age at time of surgery) 
3.   On extracorporeal membrane oxygenation (ECMO) or ventricular assist device prior to 
surgery 
 
4.   Family requests limitation of blood products (i.e. Jehovah’s Witness) 
 
5.   Congenital bleeding disorder 
6.   Are planned to require ECMO post-op  
7.   Previously enrolled in the study  
 
 
4.4 Lifestyle Considerations 
 
 
Not applicable  
 
4.5 Screen Failures  
 
Screen failures are defined as participants who consent to participate in the clinical trial but 
are not subsequently randomly assigned to the study intervention or entered in the study. 
Demographics, screen failure details, and eligibility criteria will be collected on these 
individuals. 
 
Though children undergoing elective cardiopulmonary bypass surgery do so only once 
during the course of 18 months (which will be the length of subject recruitment for this 
study), if a participant does meet inclusion criteria twice (undergoes a second elective 
cardiopulmonary bypass surgery in the course of 18 months), he/she can be rescreened 
and re-enrolled. 
 
4.6 Strategies for Recruitment and Retention 
 
 
All children scheduled to undergo elective cardiopulmonary bypass surgery are seen in the 
outpatient cardiothoracic (CT) surgery clinic setting approximately 3-5 days prior to surgery. 
Subjects and their families will be approached for assent/consent at this outpatient visit. 
Clinical staff at these outpatient sites (at Komansky Children’s Hospital at Weill Cornell and 
Morgan Stanley Children’s Hospital at Columbia) will be educated on the inclusion/exclusion 
criteria and consenting process. They will introduce the study to the families and if willing, 
the families will be approached by a clinical research coordinator for consent. The number of 
subjects eligible as well as those enrolled will be logged and reviewed on a monthly basis. 
 
For neonates admitted for their birth and awaiting cardiac surgery, they will be approached 
in the neonatal intensive care unit by the CT surgery team. The families will be introduced to 
the study by the CT surgery team and if willing, will be approached by a clinical research 
coordinator for consent. 
 
Subjects will be enrolled regardless of gender, race, and ethnicity. To demonstrate a 
difference of 1 mL/kg/hr of post-operative bleeding between the two study groups with 80% 
power, we will need 126 subjects enrolled and transfused platelets (63 subjects/group). 
Given the need for randomization prior to the decision to transfuse (as described above in 
Section 3.1), and the estimate that 50% of patients will not require any platelet transfusions, 

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we will need to consent and randomize approximately 252 subjects. Given that the two 
centers perform approximately 500 surgeries per year and the enrollment period will be 
approximately 18 months, we will require a consent rate of 34%. 
 
We seek to enroll only children, who are considered a vulnerable participant, in order to 
understand the hemostatic efficacy of PR platelet transfusions in this population. The 
coagulation systems of infants and children are unique to adults and therefore children must 
be studied separately. Participants and/or their families will no be compensated for 
participation in the study.  
 
 
 
 
5. Registration Procedures 
 
5.1 Subject Registration (WCM only) 
 
Subjects will be registered within the WRG-CT as per the standard operating procedure 
for Subject Registration.  
 
 
 
5.2 Subject Registration (Sub-sites) 
 
Subjects will be registered as per the standard operating procedure for Subject 
Registration at Columbia. All data will be collected in a de-identified manner within 
REDCap hosted by Weill Cornell." 
 
6. Study Procedures 
 
6.1 Schedule of Assessments 
 
Table 1. Schedule of trial events 
 
 
Pre-Operative 
Visit 
Operative 
Course 
Post-Op 
Day 0 
Post-Op 
Day 1 
Post-Op 
Day 2 
Off Study 
Platelet Transfusion 
 
Given at discretion of clinical team (group assignment to be maintained 
only through first 24 hours post-operatively) 
Informed Consent 
 
X 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
Medical History 
 
X 
 
 
 
 
 
Physical Exam* 
 
X 
 
X 
X 
X 
 
Vital Signs* 
 
X 
X 
X 
X 
X 
 
Weight* 
 
 
 
X 
X 
X 
 
CBC* 
 
X 
X 
X 
X 
 

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PT/PTT, fibrinogen* 
 
 
X 
X 
 
 
 
Outcome Evaluation 
 
 
X 
X 
X 
X 
X 
Medical Record Review 
and Data Collection 
 
X 
X 
X 
X 
X 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
 
*all collected regularly as standard of care 
 
6.1.1 Screening Visit 
 
 
All children who are going elective cardiopulmonary bypass surgery are seen 
approximately 3-5 days in the CT surgery outpatient clinic as standard of care. This visit will also 
serve as the screening visit for these children. All neonates who are going elective 
cardiopulmonary bypass surgery during their birth admission are seen 2-3 days prior to surgery 
by the CT surgery team in the NICU. This consultation will also serve as the screening visit for 
these children. At this visit/consultation, the following events will occur: 
 
• 
Informed consent 
• 
Demographics 
• 
Medical history 
• 
Physical exam 
• 
Vital signs 
 
Once consented, randomization will occur at this phase, to allow for ordering from the New York 
Blood Center and so as not to delay the release of the platelet transfusion from the blood bank 
during the treatment phase. Eligible subjects will be randomly assigned to either PR or LVSD 
platelets (should they need a platelet transfusion) in a 1:1 ratio using a computer-generated 
randomization scheme stratified by surgical complexity (STS score) as developed by the 
statistical team.  
 
 
 
 
6.1.2 Treatment Phase 
 
Subjects will receive platelet transfusion(s) in the group to which they were randomized (PR vs 
LVDS) at the discretion of the clinical team for the time they are in the operating room through 
the first 24 hours post-operatively. 
 
 
 
 
 
 
6.1.2.1 Operative Course 
 
 
 
 
 
Data regarding the operative course, including vital signs, receipt of any 
hemostatic medications or blood products will be collected from the operative course. In 
addition, information regarding standard of care laboratory testing will be obtained. Of note, if 
testing is not performed as per standard of care, we will not obtain the laboratory assays only for 
the purpose of the study. Lastly, chest tube output in the OR and any adverse events in the OR 
will be collected. In summary, the following events will be recorded: 
• 
 Vital Signs 
• 
CBC, PT/PTT, fibrinogen (as obtained per standard of care) 

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• 
Outcome Evaluation 
• 
Medical Record Review and Data Collection 
• 
Adverse Events Assessment 
 
 
 
 
6.1.2.2 Post-Op Days 0-2 
 
 
 
 
Because the primary outcome is the chest tube output in the first 24 hours, the 
intervention (PR versus LVDS platelet transfusions) will only be maintained for the first 24 hours 
post—op. In other words, if a subject requires a platelet transfusion after the first 24 hours post-
op, they can receive whichever product is next available in the blood bank. During post-op days 
0-2, the following events will be recorded: 
• 
Vital Signs 
• 
Physical Exam 
• 
CBC, PT/PTT, fibrinogen (as obtained per standard of care) 
• 
Outcome Evaluation 
• 
Medical Record Review and Data Collection 
• 
Adverse Events Assessment 
 
 
6.1.3 Follow-up Phase 
 
 
Subjects will be followed through the time of discharge to determine the following 
clinical outcomes: Mechanical ventilation free days, vasoactive free days, PICU free days, 
nosocomial infections, and in-hospital mortality. All “free days” will be calculated from the days a 
patient is alive in the PICU with 28-day max (i.e. a patient who is in the PICU for 10 days and 
ventilated for 4 days will have 3 mechanical ventilation free days, a patient who is in the PICU 
30 days and ventilated 2 days will have 26 mechanical ventilation free days, and a patient who 
dies in the PICU on day 2 being mechanically ventilated the entire time will have 0 mechanical 
ventilation free days). All patients will be considered off study at time of hospital discharge. The 
following events will be recorded during the follow-up phase: 
• 
Outcome Evaluation 
• 
Medical Record Review and Data Collection  
 
7. Study Intervention 
 
7.1 Study Intervention/Device Description   
 
Enrolled subjects will receive either PR or LVDS platelets based on the group to which they 
have been randomized. Both products are generally available in the blood bank, considered 
equally safe and efficacious, and used as standard of care. 
 
7.2 Availability 
 
As both products are already supplied to the blood banks at both Weill Cornell and 
Columbia, no special ordering will be required. Given shortages in the blood supply that are 
increasingly more common, the study coordinators in transfusion medicine at each site will 
work with the clinical research coordinators to ensure the product availability for the 
upcoming scheduled surgeries. 
 
7.3 Acquisition and Accountability  
 
 
 
      Not applicable 

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7.4 Formulation, Appearance, Packaging, and Labeling  
 
As the study is unblinded, the PR and LVDS platelets will maintained their normal 
appearance, packaging and labeling as required and approved by the FDA. 
 
7.5 Product Storage and Stability 
 
The blood products will be stored as per normal protocol in the blood banks at each site. 
 
7.6 Preparation 
 
The blood products will be prepared as per standard protocols maintained in the blood 
banks at each site. 
 
7.7 Dosing and Administration 
 
Platelets will be prescribed and administered at the discretion of the clinical teams. Each 
platelet transfusion will be dosed as 10mL/kg as per standard of care. 
  
7.7.1 Dosing Delays/Dose Modifications 
 
Not applicable 
 
7.8 General Concomitant Medication and Supportive Care Guidelines 
 
All hemostatic medications and blood products (such as anti-fibrinolytics, plasma 
transfusions and cryoprecipitate) will be prescribed at the discretion of the clinical team. All 
concomitant medications will be recorded in the REDCap data collection tool. 
 
7.9 Duration of Therapy and Criteria for Removal from Study  
 
In the absence of treatment delays due to adverse event(s), treatment may continue for 
the first 24 hour post-operatively or until one of the following criteria applies: 
• 
Unacceptable adverse event(s), 
• 
Subject decides to withdraw from the study, or 
• 
General or specific changes in the subject’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator. 
 
A subject’s follow-up in the study will end after one of the following applies: 
• 
Subject’s voluntary withdrawal 
• 
Subject death 
• 
Completion of all scheduled study follow-up appointments 
• 
 
7.10  Duration of Follow Up 
 
Subjects will be followed until discharge from the hospital after removal from study or 
until death, whichever occurs first.  Subjects removed from study for unacceptable 
adverse events will be followed until resolution or stabilization of the adverse event. 
 
 

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7.11 Measures to Minimize Bias: Randomization and Blinding  
 
 
 
Stratified and permuted blocked randomization will be performed.  A series of 
randomized blocks with a defined block size will be generated for each participating site 
with a 1:1 allocation ratio.  This will allow for an equal number of patients in the PR 
platelets group and LVDS platelets group at each participating site (even in the event 
that full target accrual is not achieved).  Randomization will be stratified by site 
(Komansky Children’s Hospital/Weill Cornell vs. Morgan Stanley Children’s 
Hospital/Columbia) and STAT score (STAT 1/2 vs. STAT 3/4/5). A biostatistician from 
the Weill Cornell CTSC Biostatistics, Epidemiology and Research Design (BERD) Core 
will create the randomization list and will not be involved with the study.  The 
randomization list for each site will also reside in the Research Pharmacy at each site.  
Only the BERD statistician and the Research Pharmacies will have a copy of the 
blocked randomization list (for their respective sites). As this is an open-label study, all 
study personnel will be aware of the treatment assignments. The blocked randomization 
schemes for each participating site will be uploaded to a central REDCap database 
(housed at Weill Cornell Medicine) and each site’s Research Pharmacy will be able to 
randomize a patient at their site by using the REDCap randomization module. 
 
7.12 Study Intervention/Follow-up Compliance 
 
 
No applicable 
 
8. Study Intervention Discontinuation and Participant Discontinuation/Withdrawal 
 
Participants may withdraw voluntarily from the study or the PI may discontinue a participant 
from the study. Patients will be discontinued if they require extracorporeal membrane 
oxygenation (ECMO) post-operatively (as the volume of platelet transfusions that a child 
requires on ECMO will likely not feasibly be supported by only one type of platelets). A 
dedicated Case Report Form (CRF) page will capture the date and the specific underlying 
reason for discontinuation of study intervention or participant discontinuation/withdrawal.  
 
8.1 Discontinuation of Study Intervention 
 
Those children who unexpectedly require support from ECMO following surgery will be 
discontinued from the study intervention (as their need for platelet transfusions and risk 
of bleeding will be different due to the extracorporeal circulation of their blood). The 
decision to remain on ECMO is made in the operating room and the study team will be 
informed by the clinical team. Also, if a patient requires re-cannulation onto ECMO within 
the first 24 hours post-op (while in the PICU), they will be discontinued in the study 
intervention. There are no reasons for temporary discontinuation. 
 
Discontinuation from platelet transfusion strategy does not mean discontinuation from 
the study, and remaining study procedures should be completed as indicated by the 
study protocol.  If a clinically significant finding is identified (including, but not limited to 
changes from baseline) after enrollment, the investigator or qualified designee will 
determine if any change in participant management is needed. Any new clinically 
relevant finding will be reported as an adverse event (AE). 
 

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The data to be collected at the time of study intervention discontinuation will include the 
following: Outcome Evaluation, Medical Record Review and Data Collection, Adverse 
Events Assessment. 
 
 
8.2 Participant Discontinuation/Withdrawal from the Study 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
 
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition 
or situation occurs such that continued participation in the study would not be in the 
best interest of the participant 
• 
If the participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be recorded 
on the Case Report Form (CRF). Subjects who sign the informed consent form and are 
randomized but do not receive the study intervention may be replaced.  Subjects who 
sign the informed consent form, and are randomized and receive the study intervention, 
and subsequently withdraw, or are withdrawn or discontinued from the study, will be 
replaced. 
8.3 Lost to Follow Up 
 
 
 
Not applicable (as the entire study occurs while the subject is admitted to the hospital) 
 
9. Correlative/Special Studies  
 
Not applicable 
 
9.1 Laboratory Correlative Studies 
 
Not applicable 
 
9.2 Special Studies 
 
Not applicable 
 
10.  Measurement of Effect 
 
 
10.1 Response Criteria 
 
 
The effect of the platelet transfusions received intra-operatively and in the first 24 hours 
post-op will be measured by (1) chest tube output in the first 24 hours post-op and (2) 
total transfusions required in the first t48 hours post-op 
 

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10.2 Duration of Response  
 
Though transfused platelets typically stay in circulation for 5-7 days, we will be 
measuring the hemostatic efficacy for the first 24 hours post-operatively. 
 
10.3 Progression-Free Survival  
 
 
 
Not applicable 
 
 
 
10.4 Other Response Parameters 
 
Though not directly related, clinical outcomes, such as mortality, length of hospital stay, 
length of PICU stay, length of mechanical ventilation and length of vasoactive therapy 
will be collected. 
 
11. Data Reporting / Regulatory Considerations 
 
11.1 Data Collection 
 
 
The data collection plan for this study is to utilize REDCap to capture all treatment, 
toxicity, efficacy, and adverse event data for all enrolled subjects.  
 
11.1.1 REDCap 
 
REDCap (Research Electronic Data Capture) is a free data management 
software system that is fully supported by the Weill-Cornell Medical Center 
CTSC.  It is a tool for the creation of customized, secure data management 
systems that include Web-based data-entry forms, reporting tools, and a full 
array of security features including user and group based privileges, 
authentication using institution LDAP system, with a full audit trail of data 
manipulation and export procedures.  REDCap is maintained on CTSC-owned 
servers that are backed up nightly and support encrypted (SSL-based) 
connections.  Nationally, the software is developed, enhanced and supported 
through a multi-institutional consortium led by the Vanderbilt University CTSA. 
 
11.2 Regulatory Considerations 
 
11.2.1 Institutional Review Board/Ethics Committee Approval  
 
As required by local regulations, the Investigator will ensure all legal aspects are covered, 
and approval of the appropriate regulatory bodies obtained, before study initiation.  
Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the patients, and any other relevant study documentation will be 
submitted to the appropriate Ethics Committee. Written approval of the study and all 
relevant study information must be obtained before the study center can be initiated or the 
IP is released to the Investigator. Any necessary extensions or renewals of IRB approval 
must be obtained for changes to the study, such as amendments to the protocol, the ICF, 

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or other study documentation. The written approval of the IRB together with the approved 
ICF must be filed in the study files.  
The Investigator will report promptly to the IRB any new information that may adversely 
affect the safety of the patients or the conduct of the study. The Investigator will submit 
written summaries of the study status to the IRB as required. On completion of the study, 
the IRB will be notified that the study has ended.  
 
All agreed protocol amendments will be clearly recorded on a protocol amendment form 
and will be signed and dated by the original protocol approving signatories. All protocol 
amendments will be submitted to the relevant institutional IRB for approval before 
implementation, as required by local regulations. The only exception will be when the 
amendment is necessary to eliminate an immediate hazard to the trial participants. In this 
case, the necessary action will be taken first, with the relevant protocol amendment 
following shortly thereafter.  
Once protocol amendments or consent form modifications are implemented at the lead 
site, Weill Cornell Medicine, updated documents will be provided to participating sites, as 
applicable. Weill Cornell Medicine must approve all consent form changes prior to local 
IRB submission.  
Relevant study documentation will be submitted to the regulatory authorities of the 
participating countries, according to local/national requirements, for review and approval 
before the beginning of the study. On completion of the study, the regulatory authorities 
will be notified that the study has ended.  
 
11.2.2 Ethical Conduct of the Study  
The Investigators and all parties involved should conduct this study in adherence to the 
ethical principles based on the Declaration of Helsinki, GCP, ICH guidelines and the 
applicable national and local laws and regulatory requirements.  
 
This study will be conducted under a protocol reviewed and approved by the applicable 
ethics committees and investigations will be undertaken by scientifically and medically 
qualified persons, where the benefits of the study are in proportion to the risks. 
 
11.2.3 Informed Consent 
 
The investigator or qualified designee must obtain documented consent according to ICH-
GCP and local regulations, as applicable, from each potential subject or each subject’s 
legally authorized representative prior to participating in the research study. Subjects who 
agree to participate will sign the approved informed consent form and will be provided a 
copy of the signed document.   
 
The initial ICF, any subsequent revised written ICF and any written information provided 
to the subject must approved by IRB prior to use. The ICF will adhere to IRB requirements, 
applicable laws and regulations. 
 
Participants will be consented remotely using an electronic version of the informed 
consent form that follows federal, state, and local regulations, as applicable. We will 

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implement the following procedures for electronic informed consent. 
 
The informed consent document(s) will be sent to the subject or their Legal Authorized 
Representative (LAR), if applicable, via secure email sent by REDCap prior to the 
scheduled consent discussion. The subject or LAR will be asked to review the consent 
document prior and during the consent discussion with a study staff member via an 
approved teleconferencing service (i.e., Zoom). The study staff member will confirm the 
subject or LAR has read and has the capacity to appreciate all aspects of the information 
presented in the consent process for the research study. The subject or LAR will be 
encouraged to ask questions. If agreeing to participate, the subject or LAR will sign the 
consent form using electronic informed consent (eConsent) via REDCap. A computer, 
tablet or touch screen phone will be used to capture digital signatures. If applicable, the 
person conducting consent will also sign the electronic informed consent (eConsent) 
document in a contemporaneous manner. Subjects will be provided with a digital copy of 
the completed form via email. The informed consent discussion and process will be 
documented by the study team in the subject’s medical record or study record. 
 
If a subject does not have access to a touch screen phone, computer or tablet, cannot 
work with remote electronic informed consent, or the remote electronic informed consent 
cannot be obtained for any other reasons, the consent may be conducted and documented 
at an in-person visit prior to study activities via paper consent form or through REDCap on 
an ITS tagged device. 
 
11.2.4 Compliance with Trial Registration and Results Posting Requirements  
 
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the 
Food and Drug Administration Amendments Act (FDAAA), the Sponsor-Investigator of the 
trial is solely responsible for determining whether the trial and its results are subject to the 
requirements for submission to http://www.clinicaltrials.gov. Information posted will allow 
subjects to identify potentially appropriate trials for their disease conditions and pursue 
participation by calling a central contact number for further information on appropriate trial 
locations and trial site contact information. 
 
 
 
11.2.5 Record Retention 
 
Essential documents are those documents that individually and collectively permit 
evaluation of the study and quality of the data produced.  After completion of the study, all 
documents and data relating to the study will be kept in an orderly manner by the 
Investigator in a secure study file.  Essential documents should be retained for 2 years 
after the final marketing approval in an ICH region or for at least 2 years since the 
discontinuation of clinical development of the IP. In addition, all subjects medical records 
and other source documentation will be kept for the maximum time permitted by the 
hospital, institution, or medical practice.   
 
12. Statistical Considerations 
 
Due to feasibility and limited resources, a sample size of 126 patients will be included in 
this study.  A sample size of 63 patients (126 total) in each group achieves 90% power 

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to detect a minimum difference of 0.2 mL/kg/hr in chest tube output 24 hours after the 
cardiopulmonary bypass surgery between the group receiving pathogen-reduced (PR) 
platelet transfusions and the group receiving standard (large volume delayed sampling – 
LVDS) platelet transfusions using a two-sample t-test assuming equal variance with a 
two-sided significance level of 0.05.  
 
Based on preliminary data, only around 50% of children who undergo cardiopulmonary 
bypass surgery require platelet transfusions. Therefore, 252 patients will be enrolled and 
randomized to the study to take that into consideration.  
 
Descriptive statistics (means, medians, standard deviations, interquartile ranges, 
proportions, frequency, and percent) will be calculated for baseline characteristics to 
assess and describe the study participants (by treatment group).  Baseline comparability 
will be assessed using two-sample t-test (or Wilcoxon-rank sum test) for continuous 
baseline characteristics and the chi-square test (or Fisher’s exact test) for categorical 
baseline characteristics.  
 
Based on the understanding that 50% of the randomized participants will receive 
treatment, the following populations will be formed for the purpose of data analysis: 
 
• 
An intent-to-treat cohort, defined as all participants who were recruited into the 
study, will be used for the primary and secondary analyses in the arm in which 
they were randomized, regardless of whether treatment was given.  
• 
Per-protocol cohort, defined as all participants that continue with the platelet 
transfusion (PR platelets or LVDS platelets) 
 
All analyses will be performed in R Version 4.0.5 (R Foundation for Statistical 
Computing, Vienna, Austria).  Note: The statistical considerations section was written in 
conjunction with Charlene Thomas MS, in the Division of Biostatistics, Department of 
Population Health Sciences. 
 
12.1 Study Design/Endpoints 
 
This is an open label, randomized, clinical trial that looks to compare the post-operative 
bleeding in children who received pathogen-reduced (PR) platelet transfusions versus 
standard (large volume delayed sampling – LVDS) platelet transfusions.  
 
12.2 Sample Size/Accrual Rate 
 
252 subjects will be randomized 1:1 to pathogen-reduced (PR) platelet transfusions or 
standard (large volume delayed sampling – LVDS) platelet transfusions Randomization 
will be done in REDCap using blocks of varying sizes and stratified by site and STAT 
score. We anticipate only 50% of children will require a transfusion, leaving evaluable 63 
patients per arm.  With 63 patients per arm (126 total), and assuming a standard 
deviation of 0.4, we will have 90% power to detect a minimum mean difference of 0.2 
between the two treatment arms with a significance level of 0.050 using a two-sided two-
sample equal-variance t-test. 
 

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12.3 Stratification Factors 
 
 
 
 
 
 
Subjects will be stratified by site and STAT score (1/2 vs. 3/4/5).  
 
12.4 Analysis of Endpoints 
 
12.4.1 Analysis of Primary Endpoints 
 
The primary endpoint in this study is the chest tube output for the first 24 hours 
following cardiopulmonary bypass surgery. A two-sample t-test assuming equal 
variance or a non-parametric Wilcoxon rank-sum test will be used, as 
appropriate. All tests will be two-sided with an alpha level of 5%. Confidence 
intervals for the difference in means will also be calculated to assess precision.  
 
12.4.2 Analysis of Secondary Endpoints 
 
There are three secondary endpoints in this study. First, we will compare the total 
dose red blood cell transfusions in the first 48 hours between the two arms.  
Secondly, we will compare the total blood products transfused (intra and post-
operatively) in the first 48 hours between the two arms. Lastly, rate of nosocomial 
infections between the two treatment arms will be compared. For the first two 
secondary endpoints, the two-sample t-test or non-parametric Wilcoxon rank-
sum test will be used, as appropriate.  For the last secondary endpoint, a Chi-
square test or Fisher’s exact test will be used as appropriate.   
 
12.5 Interim Analysis  
 
The DSMB will conduct regular reviews regarding the efficacy or futility of the treatment. 
If patients receiving PR platelets have > 20% bleeding as compared to LVDS platelets at 
the time of the interim analysis, the trial will be stopped. Interim analyses will be conducted 
by the study team three times during the course of the study with the enrollment and 
transfusion of every 42 patients. 
 
 
 12.6 Reporting and Exclusions 
 
12.6.1 Evaluation of Toxicity 
 
All subjects will be evaluable for toxicity from the time of their first treatment with 
Investigational Agent. Consultation with the Biostatistics Office will allow for completion 
of this section. 
 
12.6.2 Evaluation of Response 
 
All subjects included in the study will be assessed for response to treatment if they have 
received at least XX treatments.  Consultation with the Biostatistics Office will allow for 
completion of this section. 
 
 

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13. Adverse Event Reporting Requirements  
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
investigator will be required to provide appropriate information concerning any findings that 
suggest significant hazards, contraindications, side effects, or precautions pertinent to the safe 
use of the drug or device under investigation.  Safety will be monitored by evaluation of adverse 
events reported by subjects or observed by investigators or research staff, as well as by other 
investigations such as clinical laboratory tests, x-rays, electrocardiographs, etc. 
 
13.1 Adverse Event Definition 
 
An adverse event (also referred to as an adverse experience) can be any unfavorable 
and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a drug, and does not imply any judgment about 
causality. An adverse event can arise with any use of the drug (e.g., off-label use, use in 
combination with another drug) and with any route of administration, formulation, or 
dose, including an overdose.  
 
 
13.1.1 Investigational Agent or Device Risks (Expected Adverse Events) 
 
 
 
Not applicable 
 
13.1.2 Adverse Event Characteristics and Related Attributions 
 
CTCAE term (AE description) and grade:  The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting.  A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site (http://ctep.cancer.gov). 
 
• 
Attribution of the AE: 
- Definite – The AE is clearly related to the study treatment. 
- Probable – The AE is likely related to the study treatment. 
- Possible – The AE may be related to the study treatment. 
- Unlikely – The AE is doubtfully related to the study treatment. 
- Unrelated – The AE is clearly NOT related to the study treatment. 
 
 
 
13.1.3 Recording of Adverse Events 
 
All adverse events will be recorded on a subject specific AE log. The AE log will be 
maintained by the research staff and kept in the subject’s research chart.    
 
 
13.1.4 Reporting of AE to WCM IRB 
 
All AEs occurring on this study will be reported to the IRB according to the IRB policy, 
which can be accessed via the following link:  
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting
_Policy.pdf.  
 
13.1.5 Reporting Events to Participants 
 

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Not applicable 
 
13.1.6 Events of Special Interest 
 
 
Not applicable 
13.1.7 Reporting of Pregnancy 
 
 
Not applicable 
 
13.2 Definition of SAE 
 
SAEs include death, life threatening adverse experiences, hospitalization or 
prolongation of hospitalization, disability or incapacitation, overdose, congenital 
anomalies and any other serious events that may jeopardize the subject or require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition.  
 
13.2.1 Reporting of SAE to IRB 
 
All SAEs occurring on this study will be reported to the IRB according to the IRB policy, 
which can be accessed via the following link:   
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting
_Policy.pdf.  
 
13.2.2 Reporting of SAE to FDA  
 
 
Not applicable 
 
 
13.3 AE/SAE Follow Up 
 
All SAEs and AEs reported during this study will be followed until resolution or until the 
investigator confirms that the AE/SAE has stabilized and no more follow-up is required. 
This requirement indicates that follow-up may be required for some events after the 
subject discontinues participation from the study.  
 
13.4 Time Period and Frequency for Event Assessment and Follow Up 
 
The occurrence of an AE or SAE may come to the attention of study personnel during 
follow-up, medical record review or interviews with the clinical team. Because these 
subjects are inpatient and monitored closely, most AEs will be identified by clinical 
reports including laboratory findings, progress notes, nursing notes, etc. The local 
research team will monitor each subject daily for pre-defined AEs, particularly 
transfusion reactions. The research team will interview the clinical team and review the 
medical records daily for these events. The site PI or his/her designee will conduct 
prompt investigations of all reported AEs. All AEs including local and systemic reactions 
not meeting the criteria for SAEs will be captured on the appropriate CRF. Information to 
be collected includes event description, time of onset, clinician’s assessment of severity, 
initial assessment of relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the 
event. All AEs occurring while on study must be documented appropriately regardless of 

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relationship. All AEs will be followed to adequate resolution. Any medical condition that 
is present at the time that the subject is screened will be considered as baseline and not 
reported as an AE. However, if the study subject’s condition deteriorates at any time 
during the trial, it will be recorded as an AE. Changes in the severity of an AE will be 
documented to allow an assessment of the duration of the event at each level of severity 
to be performed. AEs characterized as intermittent require documentation of onset and 
duration of each episode. AEs will be followed for outcome information until resolution or 
stabilization. 
 
14. Unanticipated Problems Involving Risks to Subjects or Others 
 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others 
(UPIRTSO) 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to participants or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized. 
 
 
14.1.2 Unanticipated Problem Reporting 
 
The investigator will report unanticipated problems (UPIRTSOs) to the reviewing 
Institutional Review Board (IRB) and to the Data Coordinating Center (DCC)/lead 
principal investigator (PI). The UPIRTSO report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the 
IRB project number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, 
or outcome represents an UPIRTSO;  
• 
A description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the UPIRTSO. 
 
To satisfy the requirement for prompt reporting, UPIRTSOs will be reported using the 
following timeline:   
 
• 
UPIRTSOs that are serious adverse events (SAEs) will be reported to the IRB 
and to the DCC/study sponsor within 72 hours of the investigator becoming 
aware of the event.  

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• 
Any other UPIRTSO will be reported to the IRB and to the DCC/study sponsor 
within 72 hours of the investigator becoming aware of the problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or 
designee), Food and Drug Administration (FDA), and the Office for Human 
Research Protections (OHRP) within applicable policies of the IRB’s receipt of 
the report of the problem from the investigator. 
 
 
15. Data and Safety Monitoring Plan (DSMP) 
 
The Weill Cornell DSMB will be responsible for subject safety and will have the authority to stop 
or modify the study. The DSMB will hold the principal investigator responsible for data quality 
and completeness, and for ensuring the safety of all children in the study. Members of the 
DSMB will be independent from the study conduct and free of conflict of interest.  
 
The DSMB will meet at least semi-annually to assess safety and efficacy data (in terms of chest 
tube output, total transfusions and any transfusion reactions) on each arm of the trial. The 
DSMB will operate under the rules of an approved charter that will be written and reviewed at 
the organizational meeting of the DSMB. The DSMB will provide its input to the principal 
investigator and IRBs. 
 
This trial may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for trial suspension or 
termination, will be provided by the suspending or terminating party to the site PIs and 
regulatory authorities. If the trial is prematurely terminated or suspended, the PI will promptly 
inform the IRBs at Weill Cornell and Columbia, and will provide the reason(s) for the termination 
or suspension. Circumstances that may warrant termination or suspension include, but are not 
limited to:  
 
• Determination of unexpected, significant, or unacceptable risk to subjects  
 
• Demonstration of efficacy that would warrant stopping  
 
• Insufficient compliance to protocol requirements  
 
• Data that are not sufficiently complete and/or evaluable  
 
• Determination that the primary outcome has been met  
 
• Determination of futility 
The trial may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the DSMB and IRBs. The trial will be stopped if children receiving PR 
platelets have > 20% more bleeding as compared to children receiving LVDS platelets. 
 
 
 
 

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16. References 
 
1. 
Cholette JM, Faraoni D, Goobie SM, Ferraris V, Hassan N: Patient Blood 
Management in Pediatric Cardiac Surgery: A Review. Anesth Analg 2018, 
127(4):1002-1016. 
2. 
Closson R, Mauer E, Stock A, Dayton JD, LaPar DJ, Walline MC, Nellis ME: The 
Use of Hemostatic Blood Products in Children Following Cardiopulmonary 
Bypass and Associated Outcomes. Crit Care Explor 2020, 2(8):e0172. 
3. 
Hanson SJ, Karam O, Birch R, Goel R, Patel RM, Sola-Visner M, Sachais BS, 
Hauser RG, Luban NLC, Gottschall J et al: Transfusion Practices in Pediatric 
Cardiac Surgery Requiring Cardiopulmonary Bypass: A Secondary Analysis of 
a Clinical Database. Pediatr Crit Care Med 2021. 
4. 
Oakley FD, Woods M, Arnold S, Young PP: Transfusion reactions in pediatric 
compared with adult patients: a look at rate, reaction type, and associated 
products. Transfusion 2015, 55(3):563-570. 
5. 
Nellis ME, Karam O, Mauer E, Cushing MM, Davis PJ, Steiner ME, Tucci M, 
Stanworth SJ, Spinella PC: Platelet Transfusion Practices in Critically Ill 
Children. Crit Care Med 2018, 46(8):1309-1317. 
6. 
Brecher ME, Hay SN: Bacterial contamination of blood components. Clin 
Microbiol Rev 2005, 18(1):195-204. 
7. 
Blajchman MA, Beckers EA, Dickmeiss E, Lin L, Moore G, Muylle L: Bacterial 
detection of platelets: current problems and possible resolutions. Transfus 
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8. 
McDonald CP, Bearne J, Aplin K, Sawicka D: Assessing the inactivation 
capabilities of two commercially available platelet component pathogen 
inactivation systems: effectiveness at end of shelf life. Vox Sang 2021, 
116(4):416-424. 
9. 
Lanteri MC, Santa-Maria F, Laughhunn A, Girard YA, Picard-Maureau M, 
Payrat JM, Irsch J, Stassinopoulos A, Bringmann P: Inactivation of a broad 
spectrum of viruses and parasites by photochemical treatment of plasma 
and platelets using amotosalen and ultraviolet A light. Transfusion 2020, 
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10. 
Schmidt M, Hourfar MK, Sireis W, Pfeiffer U, Göttig S, Kempf VA, McDonald 
CP, Seifried E: Evaluation of the effectiveness of a pathogen inactivation 
technology against clinically relevant transfusion-transmitted bacterial 
strains. Transfusion 2015, 55(9):2104-2112. 
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Sim J, Tsoi WC, Lee CK, Leung R, Lam CCK, Koontz C, Liu AY, Huang N, 

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Benjamin RJ, Vermeij HJ et al: Transfusion of pathogen-reduced platelet 
components without leukoreduction. Transfusion 2019, 59(6):1953-1961. 
12. 
Cid J, Escolar G, Lozano M: Therapeutic efficacy of platelet components 
treated with amotosalen and ultraviolet A pathogen inactivation method: 
results of a meta-analysis of randomized controlled trials. Vox Sang 2012, 
103(4):322-330. 
13. 
Estcourt LJ, Malouf R, Hopewell S, Trivella M, Doree C, Stanworth SJ, Murphy 
MF: Pathogen-reduced platelets for the prevention of bleeding. Cochrane 
Database Syst Rev 2017, 7(7):Cd009072. 
14. 
Schulz WL, McPadden J, Gehrie EA, Bahar B, Gokhale A, Ross R, Price N, 
Spencer BR, Snyder E: Blood Utilization and Transfusion Reactions in 
Pediatric Patients Transfused with Conventional or Pathogen Reduced 
Platelets. J Pediatr 2019, 209:220-225. 
15. 
Trakhtman P, Karpova O, Balashov D, Kurnikova E, Pirumova V, Starostin N, 
Rumiantsev A: Efficacy and safety of pathogen-reduced platelet 
concentrates in children with cancer: a retrospective cohort study. 
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