RECESS: Red Cell Storage Duration Study

• Sponsor: HealthCore-NERI (Other)
• Overall Status: Completed
• CT.gov ID: NCT00991341
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 1,481
• Locations: 33
• Arms: 2
• Duration (Months): 49.9
• Patients Per Site: 44.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The RECESS study will compare the effects of transfusing red blood cell units stored <= 10 days vs. red blood cell units stored >= 21 days, in patients who are undergoing complex cardiac surgery and are likely to need a red blood cell transfusion. The primary hypothesis is that there is a clinically important difference between the effects of shorter-storage red cell units and longer-storage red cell units on clinical outcomes and mortality risk.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Surgery; Erythrocyte Transfusion	Biological: Red blood cell units stored <= 10 days; Biological: Red blood cell units stored >= 21 days	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1481 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Red Cell Storage Duration Study
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Shorter-storage red blood cell units Red blood cell units stored <= 10 days	Biological: Red blood cell units stored <= 10 days; Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Active Comparator: Longer-storage red blood cell units Red blood cell units stored >= 21 days	Biological: Red blood cell units stored >= 21 days; Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.

Outcome Measures

Primary Outcome Measures

1. The Change in the Composite Multiple Organ Dysfunction Score (MODS) From the Pre-operative Baseline. The Worst Post-operative Values of Each Component of MODS Will be Used to Calculate the Change in MODS. [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

   The follow-up MODS used to calculate 7-day ΔMODS from pre-op baseline was based on the worst value of each component of MODS observed through post-op day 7, hospital discharge, or death, whichever occurred first, even if a subject's worst values for different components occurred on different dates. Subjects who died during this time period were assigned the worst possible follow-up MODS score, 24 points, and each component of MODS was set at 4, which is the worst score. If a subject did not die during this time period but had at least one day where the Glasgow Coma Score couldn't be scored [subject sedated; neurologic function not normal by pre-op history (prior stroke, tumor or trauma sequelae, cognitively challenged, behavioral disorder, etc.) or intra-op history, but currently unable to assess because of sedation], then a post-op MODS score was set to missing and a 7-day ΔMODS was not computed. The total MODS score ranges from 0 (best possible) to 24 points (worst possible).

Secondary Outcome Measures

1. All-cause Mortality [28 days post-surgery]

   Subjects were randomized for RECESS no earlier than one calendar day before the planned date of surgery, and were followed for all-cause mortality until post-operative Day 28, death, or study withdrawal, whichever occurred first. In some cases the surgery was postponed after randomization had already occurred. If surgery did not occur within 30 days after randomization, the subject ended the study and was not considered evaluable. If surgery did occur within 30 days after randomization, and the subject received at least one RBC transfusion between randomization and 96 hours after the end of surgery, the subject was considered evaluable. Therefore, in a few evaluable subjects, post-operative Day 28 could be nearly two months after the date of randomization. The times in the time-to-event analysis started at randomization.

2. Change in Multiple Organ Dysfunction Score From Pre-operative Baseline. [Through 28 days post-surgery, hospital discharge, or death, whichever occurs first]

   The follow-up MODS used to calculate 28-day ΔMODS from pre-op baseline was based on the worst value of each component of MODS observed through post-op day 28, hospital discharge, or death, whichever occurred first, even if a subject's worst values for different components occurred on different dates. Subjects who died during this time period were assigned the worst possible follow-up MODS score, 24 points, and each component of MODS was set at 4, which is the worst score. If a subject did not die during this time period but had at least one day where the Glasgow Coma Score couldn't be scored[subject sedated; neurologic function not normal by pre-op history (prior stroke, tumor or trauma sequelae, cognitively challenged, behavioral disorder, etc.) or intra-op history, but currently unable to assess because of sedation], then a post-op MODS score was set to missing and a 28-day ΔMODS was not computed. The total MODS score ranges from 0 (best possible) to 24 points (worst possible).

3. Composite of Major In-hospital Post-operative Complications (Death, Stroke, Myocardial Infarction, Renal Failure, Culture-proven Sepsis/Septic Shock) [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

4. Composite of Major Cardiac Events (Death, Myocardial Infarction, Low Cardiac Output, Ventricular Tachycardia, Ventricular Fibrillation) [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

5. Composite of Major Pulmonary Events (Any Mechanical Ventilation From 48 Hours Post-operation to Day 7, Hospital Discharge or Death, Whichever Comes First, or Pulmonary Embolism) [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

6. Ventilation Duration [Through post-operative day 28, hospital discharge, or death, whichever occurs first]

   Because some subjects may experience multiple periods of ventilator use, the total duration that they were on a ventilator was compared between the two groups.

7. Change in Serum Creatinine From Pre-operative Value to Worst Post-operative Value [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

8. Change in Troponin-I From Pre-operative Value to Worst Post-operative Value [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

9. Change in Lactate From Pre-operative Value to Worst Post-operative Value [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

   The arterial lactate levels were adjusted to make them comparable to venous lactate levels.

10. Change in Bilirubin From Pre-operative Value to Worst Post-operative Value [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

11. Change in ALT From Pre-operative Value to Worst Post-operative Value (for Pediatric Subjects Only) [Through post-operative day 7, hospital discharge, or death, whichever occurs first]

12. Days to First Bowel Movement [Through post-operative day 28, hospital discharge, or death, whichever occurs first]

    Subjects were randomized for RECESS no earlier than one calendar day before the planned date of surgery, and were followed until post-operative Day 28, death, or study withdrawal, whichever occurred first. In some cases the surgery was postponed after randomization had already occurred. If surgery did not occur within 30 days after randomization, the subject ended the study and was not considered evaluable. If surgery did occur within 30 days after randomization, and the subject received at least one RBC transfusion between randomization and 96 hours after the end of surgery, the subject was considered evaluable. Therefore, in a few evaluable subjects, post-operative Day 28 could be nearly two months after the date of randomization. The times in the time-to-event analyses are from randomization to first post-operative bowel movement.

13. Days to First Solid Food [Through post-operative day 28, hospital discharge, or death, whichever occurs first]

    Subjects were randomized for RECESS no earlier than one calendar day before the planned date of surgery, and were followed until post-operative Day 28, death, or study withdrawal, whichever occurred first. In some cases the surgery was postponed after randomization had already occurred. If surgery did not occur within 30 days after randomization, the subject ended the study and was not considered evaluable. If surgery did occur within 30 days after randomization, and the subject received at least one RBC transfusion between randomization and 96 hours after the end of surgery, the subject was considered evaluable. Therefore, in a few evaluable subjects, post-operative Day 28 could be nearly two months after the date of randomization. The times in the time-to-event analyses are from randomization to first post-operative solid food.

14. Days Alive and Ventilator Free Through Post-op Day 28 [Through post-op day 28]

15. Any Mechanical Ventilation More Than 48 Hours Post-operation [48 hours post-operation through day 28, hospital discharge, or death, whichever occurs first]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• = 12 years old

• = 40 kg body weight

• Scheduled complex cardiac surgery with planned use of median sternotomy.

• Patients ≥ 18 years must have a Transfusion Risk Understanding Scoring Tool (TRUST) probability score ≥ 3

Exclusion Criteria:

• Refusal of blood products

• Planned surgery is minimally invasive

• Known transfusion reaction history

• Requirement for washed products, volume reduced products, or products with additive solution removed

• Expected residual cyanosis with O2 saturation < 90

• Left ventricular assist device (LVAD) or Extracorporeal membrane oxygenation (ECMO) support pre-operatively or planned need post-operatively

• Cardiogenic shock requiring pre-operative placement of an Intra-aortic balloon pump (IABP) (IABP done for unstable angina or prophylactically for low ejection fraction is not excluded)

• Planned Deep Hypothermic Circulatory Arrest (DHCA)

• Renal dysfunction requiring pre-operative renal replacement therapies such as hemodialysis (HD) or continuous venovenous hemofiltration (CVVH)

• Planned use of alternative to heparin, e.g. bivalirudin

• Planned use of autologous or directed donations

• Prior RBC transfusion during hospitalization for the study-qualifying surgery

• Prior randomization into the RECESS study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610
2	Emory University	Atlanta	Georgia	United States	30322
3	St. Joseph Hospital	Fort Wayne	Indiana	United States	46802
4	Indiana/Ohio Heart	Fort Wayne	Indiana	United States	46804
5	University of Iowa	Iowa City	Iowa	United States	52242
6	University of Maryland	Baltimore	Maryland	United States	21201
7	Johns Hopkins University	Baltimore	Maryland	United States	21287
8	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
9	Children's Hospital Boston	Boston	Massachusetts	United States	02115
10	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
11	St. Elizabeth's Medical Center	Boston	Massachusetts	United States	02116
12	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
13	Baystate Medical Center	Springfield	Massachusetts	United States	01199
14	Fairview Southdale Hospital/University of Minnesota Medical Center Fairview	Minneapolis	Minnesota	United States	55455
15	Mayo Clinic	Rochester	Minnesota	United States	55905
16	Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
17	Newark Beth Israel Deaconess Medical Center	Newark	New Jersey	United States	07112
18	Columbia University Health Center	New York	New York	United States	10032
19	Weill Cornell Medical School	New York	New York	United States	10065
20	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
21	Duke University	Durham	North Carolina	United States	27713
22	Sanford Heart Center	Fargo	North Dakota	United States	58122
23	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
24	University of Pittsburgh Presbyterian and Shadyside	Pittsburgh	Pennsylvania	United States	15213
25	UPMC-Mercy Hospital	Pittsburgh	Pennsylvania	United States	15219
26	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37323
27	UT Southwestern	Dallas	Texas	United States	75390
28	Texas Heart Institute	Houston	Texas	United States	77030
29	Veterans Administration Puget Sound	Seattle	Washington	United States	98108
30	Swedish Medical Center	Seattle	Washington	United States	98195
31	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin	United States	53201
32	Aurora St. Lukes Medical Center	Milwaukee	Wisconsin	United States	53215
33	Aspirus Vascular Heart Center	Wausau	Wisconsin	United States	54401

Sponsors and Collaborators

• HealthCore-NERI
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Susan F Assmann, PhD, HealthCore-NERI
• Principal Investigator: Steven Sloan, MD, Boston Children's Hospital
• Principal Investigator: Thomas Ortel, MD, Duke University
• Principal Investigator: Cassandra Josephson, MD, Emory University
• Principal Investigator: Christopher Stowell, MD, Massachusetts General Hospital
• Principal Investigator: Meghan Delaney, DO, University of Washington/Fred Hutchinson Cancer Research Center
• Principal Investigator: Marie Steiner, MD, University of Minnesota Medical Center Fairview
• Principal Investigator: Darrell Triulzi, MD, University of Pittsburgh Presbyterian and Shadyside
• Principal Investigator: Lynne Uhl, MD, Beth Israel Deaconess Medical Center
• Principal Investigator: Richard Kaufman, MD, Brigham and Women's Hospital
• Principal Investigator: James Bussel, MD, Weill Medical College of Cornell University
• Principal Investigator: Paul Ness, MD, Johns Hopkins University
• Principal Investigator: Thomas Raife, MD, University of Iowa
• Principal Investigator: Rhonda Cooke, MD, University of Maryland
• Principal Investigator: Nigel Key, MD, University of North Carolina, Chapel Hill
• Principal Investigator: Jeff Carson, MD, Rutgers, The State University of New Jersey
• Principal Investigator: Vincent Scavo, MD, Indiana/Ohio Heart
• Principal Investigator: Wade Fischer, MD, FACS, Froedtert Hospital
• Principal Investigator: Pampee Young, MD, Vanderbilt University
• Principal Investigator: Kathy Puca, MD, St. Luke's Hospital
• Principal Investigator: James George, MD, University of Oklahoma
• Principal Investigator: Gregory Nuttall, MD, Mayo Clinic
• Principal Investigator: Arthur Bracey, MD, Texas Heart Institute
• Principal Investigator: Richard Engleman, MD, Baystate Medical Center
• Principal Investigator: Philip Greileich, MD, University of Texas
• Principal Investigator: Kent Berg, MD, University of Florida
• Principal Investigator: Robert Hunsaker, MD, St. Elizabeth's Medical Center
• Principal Investigator: Ronald Miles, MD, Aspirus Medical Center
• Principal Investigator: Ravindra Karanam, MD, Barnabas Health, Newark Beth Israel Medical Center
• Principal Investigator: Cornelius Dyke, MD, Sanford Heart Center
• Principal Investigator: Eldad Hod, MD, Columbia University Health Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: HealthCore-NERI
• ClinicalTrials.gov Identifier: NCT00991341
• Other Study ID Numbers: 676; U01HL072268; HL072268; HL072033; HL072291; HL072196; HL072289; HL072248; HL072191; HL072299; HL072305; HL072274; HL072028; HL072359; HL072072; HL072355; HL072283; HL072346; HL072331; HL072290
• First Posted: Oct 8, 2009
• Last Update Posted: Jun 9, 2015
• Last Verified: May 1, 2014

• Keywords provided by HealthCore-NERI: Cardiac surgery; Red blood cell; Transfusion

Study Results

Participant Flow

Recruitment Details	RECESS recruitment took place at 33 US hospitals, beginning in January 2010 and ending in January 2014.
Pre-assignment Detail	Randomization was stratified by age (≥18 yrs or <18 yrs) and by whether or not the subject was in the ICU prior to surgery. A subject could not be randomized unless prior to surgery but no earlier than one calendar day prior to surgery, the transfusion service had enough suitable units of both storage durations to satisfy the cross-match request.

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Period Title: Overall Study
STARTED	742	739
COMPLETED	538	560
NOT COMPLETED	204	179

Baseline Characteristics

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units	Total
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Total of all reporting groups
Overall Participants	538	560	1098
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	73	72	72
Age, Customized (participants) [Number]
<18 years	2 0.4%	2 0.4%	4 0.4%
>= 18 years	536 99.6%	558 99.6%	1094 99.6%
Sex: Female, Male (Count of Participants)
Female	310 57.6%	313 55.9%	623 56.7%
Male	228 42.4%	247 44.1%	475 43.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 2.4%	19 3.4%	32 2.9%
Not Hispanic or Latino	506 94.1%	513 91.6%	1019 92.8%
Unknown or Not Reported	19 3.5%	28 5%	47 4.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%	1 0.2%	2 0.2%
Asian	11 2%	8 1.4%	19 1.7%
Native Hawaiian or Other Pacific Islander	3 0.6%	1 0.2%	4 0.4%
Black or African American	32 5.9%	39 7%	71 6.5%
White	485 90.1%	493 88%	978 89.1%
More than one race	2 0.4%	3 0.5%	5 0.5%
Unknown or Not Reported	4 0.7%	15 2.7%	19 1.7%
Region of Enrollment (participants) [Number]
United States	538 100%	560 100%	1098 100%
Weight (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	75	74	75
Height (cm) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm]	165	165	165
Minimum TRUST Score (participants) [Number]
0	1 0.2%	0 0%	1 0.1%
3	166 30.9%	222 39.6%	388 35.3%
4	210 39%	196 35%	406 37%
5	132 24.5%	113 20.2%	245 22.3%
6	26 4.8%	27 4.8%	53 4.8%
7	3 0.6%	2 0.4%	5 0.5%
ICU Status at Randomization (participants) [Number]
In ICU Before Surgery	34 6.3%	33 5.9%	67 6.1%
Not in ICU Before Surgery	504 93.7%	527 94.1%	1031 93.9%
Baseline Multiple Organ Dysfunction Score (participants) [Number]
0	252 46.8%	293 52.3%	545 49.6%
1	223 41.4%	194 34.6%	417 38%
2	48 8.9%	57 10.2%	105 9.6%
3	10 1.9%	11 2%	21 1.9%
4	4 0.7%	4 0.7%	8 0.7%
5	1 0.2%	1 0.2%	2 0.2%
ABO Blood Group (participants) [Number]
O	209 38.8%	235 42%	444 40.4%
A	240 44.6%	241 43%	481 43.8%
B	64 11.9%	63 11.3%	127 11.6%
AB	25 4.6%	21 3.8%	46 4.2%
Hemoglobin (g/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [g/L]	11.7	12.0	11.9

Outcome Measures

1. Primary Outcome

Title	The Change in the Composite Multiple Organ Dysfunction Score (MODS) From the Pre-operative Baseline. The Worst Post-operative Values of Each Component of MODS Will be Used to Calculate the Change in MODS.
Description	The follow-up MODS used to calculate 7-day ΔMODS from pre-op baseline was based on the worst value of each component of MODS observed through post-op day 7, hospital discharge, or death, whichever occurred first, even if a subject's worst values for different components occurred on different dates. Subjects who died during this time period were assigned the worst possible follow-up MODS score, 24 points, and each component of MODS was set at 4, which is the worst score. If a subject did not die during this time period but had at least one day where the Glasgow Coma Score couldn't be scored [subject sedated; neurologic function not normal by pre-op history (prior stroke, tumor or trauma sequelae, cognitively challenged, behavioral disorder, etc.) or intra-op history, but currently unable to assess because of sedation], then a post-op MODS score was set to missing and a 7-day ΔMODS was not computed. The total MODS score ranges from 0 (best possible) to 24 points (worst possible).
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	534	553
Mean (Standard Deviation) [MOD score points]	8.49 (3.62)	8.66 (3.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	ANCOVA
	Comments	The treatment groups were compared with respect to the change in MODS, adjusting for baseline MODS.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage red blood cell units arm is the reference category. After adjusting for baseline MODS, the difference in the means was -0.17, positive values are in favor of longer storage duration.

2. Secondary Outcome

Title	All-cause Mortality
Description	Subjects were randomized for RECESS no earlier than one calendar day before the planned date of surgery, and were followed for all-cause mortality until post-operative Day 28, death, or study withdrawal, whichever occurred first. In some cases the surgery was postponed after randomization had already occurred. If surgery did not occur within 30 days after randomization, the subject ended the study and was not considered evaluable. If surgery did occur within 30 days after randomization, and the subject received at least one RBC transfusion between randomization and 96 hours after the end of surgery, the subject was considered evaluable. Therefore, in a few evaluable subjects, post-operative Day 28 could be nearly two months after the date of randomization. The times in the time-to-event analysis started at randomization.
Time Frame	28 days post-surgery

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	538	560
Number [participants with event]	23 4.3%	29 5.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Regression, Cox
	Comments	The treatment groups were compared with respect to all-cause mortality, adjusting for baseline MODS.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage duration arm is the reference category.

3. Secondary Outcome

Title	Change in Multiple Organ Dysfunction Score From Pre-operative Baseline.
Description	The follow-up MODS used to calculate 28-day ΔMODS from pre-op baseline was based on the worst value of each component of MODS observed through post-op day 28, hospital discharge, or death, whichever occurred first, even if a subject's worst values for different components occurred on different dates. Subjects who died during this time period were assigned the worst possible follow-up MODS score, 24 points, and each component of MODS was set at 4, which is the worst score. If a subject did not die during this time period but had at least one day where the Glasgow Coma Score couldn't be scored[subject sedated; neurologic function not normal by pre-op history (prior stroke, tumor or trauma sequelae, cognitively challenged, behavioral disorder, etc.) or intra-op history, but currently unable to assess because of sedation], then a post-op MODS score was set to missing and a 28-day ΔMODS was not computed. The total MODS score ranges from 0 (best possible) to 24 points (worst possible).
Time Frame	Through 28 days post-surgery, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	531	555
Mean (Standard Deviation) [MOD score points]	8.74 (4.04)	9.07 (4.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	ANCOVA
	Comments	The treatment groups were compared with respect to 28-day change in MODS, adjusting for baseline MODS.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.82 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage red blood cell units arm is the reference category. After adjusting for baseline MODS, the difference in the means was -0.32; positive values are in favor of longer storage duration.

4. Secondary Outcome

Title	Composite of Major In-hospital Post-operative Complications (Death, Stroke, Myocardial Infarction, Renal Failure, Culture-proven Sepsis/Septic Shock)
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	448	470
Number [participants with event]	91 16.9%	87 15.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.018
	Confidence Interval	(2-Sided) 95%; -0.033 to 0.069
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in proportions between the two treatment arms was computed as the proportion of subjects with the event in the shorter storage duration arm minus the proportion of subjects with the event in the longer storage duration arm.

5. Secondary Outcome

Title	Composite of Major Cardiac Events (Death, Myocardial Infarction, Low Cardiac Output, Ventricular Tachycardia, Ventricular Fibrillation)
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	472	496
Number [participants with event]	206 38.3%	230 41.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.027
	Confidence Interval	(2-Sided) 95%; -0.090 to 0.035
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in proportions between the two treatment arms was computed as the proportion of subjects with the event in the shorter storage duration arm minus the proportion of subjects with the event in the longer storage duration arm.

6. Secondary Outcome

Title	Composite of Major Pulmonary Events (Any Mechanical Ventilation From 48 Hours Post-operation to Day 7, Hospital Discharge or Death, Whichever Comes First, or Pulmonary Embolism)
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	508	537
Number [participants with event]	62 11.5%	75 13.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.018
	Confidence Interval	(2-Sided) 95%; -0.059 to 0.023
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in proportions between the two treatment arms was computed as the proportion of subjects with the event in the shorter storage duration arm minus the proportion of subjects with the event in the longer storage duration arm.

7. Secondary Outcome

Title	Ventilation Duration
Description	Because some subjects may experience multiple periods of ventilator use, the total duration that they were on a ventilator was compared between the two groups.
Time Frame	Through post-operative day 28, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	514	540
Mean (Standard Deviation) [days]	2.7 (3.9)	2.8 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Kruskal-Wallis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.62 to 0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in Serum Creatinine From Pre-operative Value to Worst Post-operative Value
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	532	558
Mean (Standard Deviation) [mg/dL]	0.35 (0.58)	0.35 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	ANCOVA
	Comments	The treatment arms were compared with respect to the change in creatinine, adjusting for the baseline creatinine value.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage red blood cell units arm is the reference category. After adjusting for baseline creatinine, the difference in the means was -0.02, positive values are in favor of longer storage duration.

9. Secondary Outcome

Title	Change in Troponin-I From Pre-operative Value to Worst Post-operative Value
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	443	470
Mean (Standard Deviation) [ng/mL]	15.82 (37.64)	14.06 (23.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments	Troponin-I values recorded as 'too low to detect' were recoded as 0 since the median value of the minimum quantitative troponin-I value obtained among all participating sites was 0.01.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments	The treatment arms were compared with respect to the change in troponin-I, adjusting for the baseline troponin-I value.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.93
	Confidence Interval	(2-Sided) 95%; -2.11 to 5.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage red blood cell units arm is the reference category. After adjusting for baseline troponin-I, the change in troponin-I values was 1.9 ng/mL higher in the shorter storage red blood cell units arm.

10. Secondary Outcome

Title	Change in Lactate From Pre-operative Value to Worst Post-operative Value
Description	The arterial lactate levels were adjusted to make them comparable to venous lactate levels.
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	410	437
Mean (Standard Deviation) [mmol/L]	2.30 (3.33)	2.92 (5.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Kruskal-Wallis
	Comments

11. Secondary Outcome

Title	Change in Bilirubin From Pre-operative Value to Worst Post-operative Value
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	513	543
Mean (Standard Deviation) [mg/dL]	0.85 (1.24)	1.49 (2.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -0.89 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage red blood cell units arm is the reference category. After adjusting for baseline bilirubin, the change in bilirubin values was 0.65 mg/dL lower in the shorter storage red blood cell units arm.

12. Secondary Outcome

Title	Change in ALT From Pre-operative Value to Worst Post-operative Value (for Pediatric Subjects Only)
Time Frame	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Only 4 pediatric subjects were enrolled. One treatment arm had only one subject with available data for analyzing the change in ALT. Therefore, to protect patient confidentiality, results were not entered.

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	0	0

13. Secondary Outcome

Title	Days to First Bowel Movement
Description	Subjects were randomized for RECESS no earlier than one calendar day before the planned date of surgery, and were followed until post-operative Day 28, death, or study withdrawal, whichever occurred first. In some cases the surgery was postponed after randomization had already occurred. If surgery did not occur within 30 days after randomization, the subject ended the study and was not considered evaluable. If surgery did occur within 30 days after randomization, and the subject received at least one RBC transfusion between randomization and 96 hours after the end of surgery, the subject was considered evaluable. Therefore, in a few evaluable subjects, post-operative Day 28 could be nearly two months after the date of randomization. The times in the time-to-event analyses are from randomization to first post-operative bowel movement.
Time Frame	Through post-operative day 28, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96). The mean time to an event is estimated by the area under the survival function.

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	538	560
Mean (Standard Error) [days]	5.89 (0.17)	6.62 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments	The treatment groups were compared with respect to days to first post-operative bowel movement, adjusting for baseline MODS.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage duration arm is reference category.

14. Secondary Outcome

Title	Days to First Solid Food
Description	Subjects were randomized for RECESS no earlier than one calendar day before the planned date of surgery, and were followed until post-operative Day 28, death, or study withdrawal, whichever occurred first. In some cases the surgery was postponed after randomization had already occurred. If surgery did not occur within 30 days after randomization, the subject ended the study and was not considered evaluable. If surgery did occur within 30 days after randomization, and the subject received at least one RBC transfusion between randomization and 96 hours after the end of surgery, the subject was considered evaluable. Therefore, in a few evaluable subjects, post-operative Day 28 could be nearly two months after the date of randomization. The times in the time-to-event analyses are from randomization to first post-operative solid food.
Time Frame	Through post-operative day 28, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96). The mean time to an event is estimated by the area under the survival function.

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	538	560
Mean (Standard Error) [days]	5.73 (0.37)	6.18 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Regression, Cox
	Comments	The treatment groups were compared with respect to days to first post-operative solid food, adjusting for baseline MODS.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage duration arm is reference category.

15. Secondary Outcome

Title	Days Alive and Ventilator Free Through Post-op Day 28
Time Frame	Through post-op day 28

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	511	539
Mean (Standard Deviation) [days]	25.38 (6.40)	25.17 (6.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Kruskal-Wallis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.59 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	The longer storage duration arm is reference category.

16. Secondary Outcome

Title	Any Mechanical Ventilation More Than 48 Hours Post-operation
Time Frame	48 hours post-operation through day 28, hospital discharge, or death, whichever occurs first

Outcome Measure Data

Analysis Population Description

Analysis is restricted to evaluable subjects (defined as randomized subjects who underwent cardiac surgery within 30 days after randomization and received at least one RBC transfusion between randomization and post-operative hour 96).

Arm/Group Title	Shorter-storage Red Blood Cell Units	Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.	Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
Measure Participants	508	537
Number [participants with event]	68 12.6%	80 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Shorter-storage Red Blood Cell Units, Longer-storage Red Blood Cell Units
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.015
	Confidence Interval	(2-Sided) 95%; -0.057 to 0.027
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in proportions between the two treatment arms was computed as the proportion of subjects with the event in the shorter storage duration arm minus the proportion of subjects with the event in the longer storage duration arm.

Adverse Events

Time Frame	Reported Adverse Events (AEs) include any untoward medical occurrence which occurred after a subject gave informed consent and no later than post-operative day 28, hospital discharge, or death, whichever came first.
Adverse Event Reporting Description	Data were collected on all serious adverse events (SAEs) and on pre-specified types of non-serious adverse events. If a subject experiences more than one occurrence of a specific adverse event, the subject was counted only once for that adverse event.
Arm/Group Title	Shorter-storage Red Blood Cell Units		Longer-storage Red Blood Cell Units
Arm/Group Description	Red blood cell units stored <= 10 days Red blood cell units stored <= 10 days: Pre-storage leukoreduced red blood cell units stored <=10 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.		Red blood cell units stored >= 21 days Red blood cell units stored >= 21 days: Pre-storage leukoreduced red blood cell units stored >=21 days at time of transfusion. Can be AS1, AS3, or AS5. Frozen, deglycerolized, washed, and volume-reduced products are protocol violations.
All Cause Mortality
	Shorter-storage Red Blood Cell Units		Longer-storage Red Blood Cell Units
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Shorter-storage Red Blood Cell Units		Longer-storage Red Blood Cell Units
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	283/538 (52.6%)		288/560 (51.4%)
Blood and lymphatic system disorders
Anaemia	0/538 (0%)	0	2/560 (0.4%)	2
Autoimmune thrombocytopenia	1/538 (0.2%)	1	1/560 (0.2%)	1
Coagulopathy	2/538 (0.4%)	2	2/560 (0.4%)	2
Disseminated intravascular coagulation	0/538 (0%)	0	1/560 (0.2%)	1
Haemolytic anaemia	1/538 (0.2%)	1	0/560 (0%)	0
Heparin-induced thrombocytopenia	5/538 (0.9%)	5	3/560 (0.5%)	3
Leukocytosis	7/538 (1.3%)	7	4/560 (0.7%)	5
Thrombocytopenia	1/538 (0.2%)	1	4/560 (0.7%)	4
Cardiac disorders
Accelerated idioventricular rhythm	3/538 (0.6%)	4	0/560 (0%)	0
Acute coronary syndrome	1/538 (0.2%)	1	0/560 (0%)	0
Acute myocardial infarction	9/538 (1.7%)	9	9/560 (1.6%)	9
Acute right ventricular failure	2/538 (0.4%)	2	1/560 (0.2%)	1
Angina pectoris	2/538 (0.4%)	2	0/560 (0%)	0
Angina unstable	0/538 (0%)	0	1/560 (0.2%)	1
Arrhythmia	1/538 (0.2%)	1	2/560 (0.4%)	2
Arrhythmia supraventricular	0/538 (0%)	0	1/560 (0.2%)	1
Atrial fibrillation	31/538 (5.8%)	33	25/560 (4.5%)	28
Atrial flutter	3/538 (0.6%)	3	1/560 (0.2%)	1
Atrial tachycardia	3/538 (0.6%)	3	3/560 (0.5%)	3
Atrioventricular block	1/538 (0.2%)	1	1/560 (0.2%)	1
Atrioventricular block complete	3/538 (0.6%)	3	3/560 (0.5%)	3
Atrioventricular block first degree	1/538 (0.2%)	1	0/560 (0%)	0
Bradycardia	7/538 (1.3%)	9	10/560 (1.8%)	10
Cardiac arrest	3/538 (0.6%)	4	4/560 (0.7%)	4
Cardiac disorder	1/538 (0.2%)	1	0/560 (0%)	0
Cardiac failure congestive	2/538 (0.4%)	2	3/560 (0.5%)	3
Cardiac tamponade	6/538 (1.1%)	6	5/560 (0.9%)	6
Cardio-respiratory arrest	1/538 (0.2%)	1	0/560 (0%)	0
Cardiogenic shock	9/538 (1.7%)	9	13/560 (2.3%)	13
Cardiomyopathy acute	0/538 (0%)	0	1/560 (0.2%)	1
Conduction disorder	0/538 (0%)	0	1/560 (0.2%)	1
Intracardiac thrombus	0/538 (0%)	0	1/560 (0.2%)	1
Myocardial infarction	1/538 (0.2%)	1	1/560 (0.2%)	1
Negative cardiac inotropic effect	0/538 (0%)	0	1/560 (0.2%)	1
Nodal arrhythmia	1/538 (0.2%)	1	0/560 (0%)	0
Pericardial effusion	3/538 (0.6%)	3	0/560 (0%)	0
Sick sinus syndrome	0/538 (0%)	0	2/560 (0.4%)	2
Sinus bradycardia	20/538 (3.7%)	20	24/560 (4.3%)	24
Sinus tachycardia	16/538 (3%)	17	26/560 (4.6%)	28
Supraventricular tachyarrhythmia	3/538 (0.6%)	3	2/560 (0.4%)	2
Supraventricular tachycardia	0/538 (0%)	0	3/560 (0.5%)	3
Tachycardia	0/538 (0%)	0	5/560 (0.9%)	6
Ventricular arrhythmia	1/538 (0.2%)	1	1/560 (0.2%)	1
Ventricular asystole	2/538 (0.4%)	2	2/560 (0.4%)	2
Ventricular extrasystoles	1/538 (0.2%)	1	2/560 (0.4%)	2
Ventricular fibrillation	4/538 (0.7%)	4	6/560 (1.1%)	6
Ventricular tachyarrhythmia	3/538 (0.6%)	4	4/560 (0.7%)	4
Ventricular tachycardia	6/538 (1.1%)	9	7/560 (1.3%)	8
Congenital, familial and genetic disorders
Familial hypocalciuric hypercalcaemia	1/538 (0.2%)	1	0/560 (0%)	0
Heart block congenital	1/538 (0.2%)	1	2/560 (0.4%)	2
Ear and labyrinth disorders
Vertigo	0/538 (0%)	0	1/560 (0.2%)	1
Endocrine disorders
Antidiuretic hormone abnormality	1/538 (0.2%)	1	0/560 (0%)	0
Eye disorders
Visual acuity reduced transiently	0/538 (0%)	0	1/560 (0.2%)	1
Visual impairment	1/538 (0.2%)	1	0/560 (0%)	0
Gastrointestinal disorders
Abdominal compartment syndrome	0/538 (0%)	0	1/560 (0.2%)	1
Abdominal distension	1/538 (0.2%)	1	1/560 (0.2%)	1
Ascites	0/538 (0%)	0	1/560 (0.2%)	1
Colitis	1/538 (0.2%)	1	0/560 (0%)	0
Colonic obstruction	1/538 (0.2%)	1	0/560 (0%)	0
Dysphagia	3/538 (0.6%)	3	1/560 (0.2%)	1
Gastric haemorrhage	1/538 (0.2%)	1	2/560 (0.4%)	2
Gastric perforation	0/538 (0%)	0	1/560 (0.2%)	1
Gastrointestinal haemorrhage	1/538 (0.2%)	1	2/560 (0.4%)	2
Ileus	1/538 (0.2%)	1	0/560 (0%)	0
Ileus paralytic	1/538 (0.2%)	1	0/560 (0%)	0
Internal hernia	1/538 (0.2%)	1	0/560 (0%)	0
Lower gastrointestinal haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
Megacolon	1/538 (0.2%)	1	0/560 (0%)	0
Mesenteric occlusion	0/538 (0%)	0	1/560 (0.2%)	1
Oesophageal perforation	1/538 (0.2%)	1	0/560 (0%)	0
Peritoneal haemorrhage	1/538 (0.2%)	1	0/560 (0%)	0
Pneumoperitoneum	1/538 (0.2%)	1	0/560 (0%)	0
Retroperitoneal haematoma	1/538 (0.2%)	1	0/560 (0%)	0
Retroperitoneal haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
Upper gastrointestinal haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
General disorders
Adverse drug reaction	0/538 (0%)	0	1/560 (0.2%)	1
Application site bleeding	13/538 (2.4%)	13	11/560 (2%)	11
Cardiac death	0/538 (0%)	0	1/560 (0.2%)	1
Chest discomfort	2/538 (0.4%)	2	0/560 (0%)	0
Chest pain	1/538 (0.2%)	1	0/560 (0%)	0
Infusion related reaction	1/538 (0.2%)	1	0/560 (0%)	0
Infusion site dermatitis	0/538 (0%)	0	1/560 (0.2%)	1
Multi-organ disorder	1/538 (0.2%)	1	0/560 (0%)	0
Multi-organ failure	3/538 (0.6%)	3	3/560 (0.5%)	3
Pyrexia	1/538 (0.2%)	1	0/560 (0%)	0
Hepatobiliary disorders
Hepatic cirrhosis	0/538 (0%)	0	1/560 (0.2%)	1
Hepatic ischaemia	1/538 (0.2%)	1	0/560 (0%)	0
Hyperbilirubinaemia	26/538 (4.8%)	28	51/560 (9.1%)	58
Liver injury	1/538 (0.2%)	1	0/560 (0%)	0
Pneumobilia	1/538 (0.2%)	1	0/560 (0%)	0
Immune system disorders
Anaphylactoid shock	1/538 (0.2%)	1	0/560 (0%)	0
Infections and infestations
Abdominal infection	1/538 (0.2%)	2	2/560 (0.4%)	2
Abdominal sepsis	0/538 (0%)	0	2/560 (0.4%)	2
Acute endocarditis	0/538 (0%)	0	1/560 (0.2%)	1
Adenoviral upper respiratory infection	2/538 (0.4%)	2	0/560 (0%)	0
Bacterial diarrhoea	1/538 (0.2%)	1	0/560 (0%)	0
Bacterial infection	0/538 (0%)	0	1/560 (0.2%)	1
Bacterial sepsis	3/538 (0.6%)	3	6/560 (1.1%)	6
Bronchitis	0/538 (0%)	0	1/560 (0.2%)	1
Bronchitis pneumococcal	1/538 (0.2%)	1	0/560 (0%)	0
Bronchopneumonia	11/538 (2%)	12	9/560 (1.6%)	9
Candida pneumonia	0/538 (0%)	0	1/560 (0.2%)	1
Cellulitis	3/538 (0.6%)	3	0/560 (0%)	0
Clostridium colitis	1/538 (0.2%)	1	0/560 (0%)	0
Clostridium difficile colitis	3/538 (0.6%)	3	3/560 (0.5%)	3
Cystitis	0/538 (0%)	0	1/560 (0.2%)	1
Cystitis klebsiella	0/538 (0%)	0	1/560 (0.2%)	1
Endocarditis	1/538 (0.2%)	1	0/560 (0%)	0
Enterobacter infection	0/538 (0%)	0	1/560 (0.2%)	1
Enterobacter pneumonia	0/538 (0%)	0	2/560 (0.4%)	2
Enterococcal infection	1/538 (0.2%)	1	0/560 (0%)	0
Escherichia urinary tract infection	1/538 (0.2%)	1	1/560 (0.2%)	1
Febrile infection	1/538 (0.2%)	1	3/560 (0.5%)	3
Genitourinary tract infection	8/538 (1.5%)	9	6/560 (1.1%)	6
Incision site infection	1/538 (0.2%)	1	1/560 (0.2%)	1
Infection	0/538 (0%)	0	1/560 (0.2%)	1
Lung infection	0/538 (0%)	0	1/560 (0.2%)	1
Osteomyelitis	0/538 (0%)	0	1/560 (0.2%)	1
Pneumonia klebsiella	1/538 (0.2%)	1	0/560 (0%)	0
Post procedural infection	1/538 (0.2%)	1	0/560 (0%)	0
Postoperative wound infection	0/538 (0%)	0	2/560 (0.4%)	2
Pseudomonal bacteraemia	0/538 (0%)	0	1/560 (0.2%)	1
Pseudomonas infection	0/538 (0%)	0	1/560 (0.2%)	1
Sepsis syndrome	1/538 (0.2%)	1	0/560 (0%)	0
Septic shock	1/538 (0.2%)	1	1/560 (0.2%)	1
Serratia infection	0/538 (0%)	0	1/560 (0.2%)	1
Upper respiratory tract infection	0/538 (0%)	0	1/560 (0.2%)	1
Urinary tract infection	2/538 (0.4%)	2	1/560 (0.2%)	1
Injury, poisoning and procedural complications
Airway complication of anaesthesia	1/538 (0.2%)	1	0/560 (0%)	0
Allergic transfusion reaction	0/538 (0%)	0	1/560 (0.2%)	1
Anaphylactic transfusion reaction	0/538 (0%)	0	1/560 (0.2%)	1
Cardiac function disturbance postoperative	0/538 (0%)	0	1/560 (0.2%)	1
Cardiac valve replacement complication	1/538 (0.2%)	1	0/560 (0%)	0
Confusion postoperative	1/538 (0.2%)	1	0/560 (0%)	0
Deep vein thrombosis postoperative	1/538 (0.2%)	1	4/560 (0.7%)	4
Endotracheal intubation complication	0/538 (0%)	0	1/560 (0.2%)	1
Fall	1/538 (0.2%)	1	0/560 (0%)	0
Iatrogenic injury	1/538 (0.2%)	1	0/560 (0%)	0
Mental status changes postoperative	0/538 (0%)	0	2/560 (0.4%)	2
Operative haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
Pneumothorax traumatic	1/538 (0.2%)	1	0/560 (0%)	0
Post procedural complication	1/538 (0.2%)	1	1/560 (0.2%)	1
Post procedural haemorrhage	1/538 (0.2%)	1	6/560 (1.1%)	6
Post procedural myocardial infarction	1/538 (0.2%)	1	1/560 (0.2%)	1
Postoperative ileus	1/538 (0.2%)	1	1/560 (0.2%)	1
Postoperative renal failure	3/538 (0.6%)	3	3/560 (0.5%)	3
Procedural hypotension	3/538 (0.6%)	3	9/560 (1.6%)	9
Renal injury	2/538 (0.4%)	2	2/560 (0.4%)	2
Subdural haematoma	0/538 (0%)	0	1/560 (0.2%)	1
Urinary retention postoperative	10/538 (1.9%)	10	10/560 (1.8%)	10
Weaning failure	1/538 (0.2%)	1	0/560 (0%)	0
Wound dehiscence	2/538 (0.4%)	2	1/560 (0.2%)	1
Wound necrosis	0/538 (0%)	0	1/560 (0.2%)	1
Investigations
Activated partial thromboplastin time	0/538 (0%)	0	1/560 (0.2%)	1
Anticoagulation drug level below therapeutic	1/538 (0.2%)	1	0/560 (0%)	0
Aspiration pleural cavity	1/538 (0.2%)	1	1/560 (0.2%)	1
Bacteria blood identified	1/538 (0.2%)	1	0/560 (0%)	0
Bacteria sputum identified	0/538 (0%)	0	1/560 (0.2%)	1
Blood gases abnormal	0/538 (0%)	0	1/560 (0.2%)	1
Blood pressure abnormal	0/538 (0%)	0	1/560 (0.2%)	1
Blood pressure decreased	6/538 (1.1%)	6	5/560 (0.9%)	5
Blood pressure systolic decreased	1/538 (0.2%)	1	0/560 (0%)	0
Blood urea nitrogen/creatinine ratio increased	1/538 (0.2%)	1	0/560 (0%)	0
Blood urine present	1/538 (0.2%)	1	1/560 (0.2%)	1
Body temperature decreased	2/538 (0.4%)	2	0/560 (0%)	0
Body temperature increased	2/538 (0.4%)	2	3/560 (0.5%)	3
Bronchoalveolar lavage abnormal	0/538 (0%)	0	1/560 (0.2%)	1
Cardiac enzymes increased	2/538 (0.4%)	2	2/560 (0.4%)	2
Cardiac output decreased	1/538 (0.2%)	1	0/560 (0%)	0
Clostridium difficile toxin test positive	0/538 (0%)	0	1/560 (0.2%)	1
ECG signs of myocardial ischaemia	4/538 (0.7%)	4	2/560 (0.4%)	2
Ejection fraction decreased	0/538 (0%)	0	1/560 (0.2%)	1
Fungus culture positive	1/538 (0.2%)	1	0/560 (0%)	0
Heart rate decreased	0/538 (0%)	0	2/560 (0.4%)	2
Heart rate increased	0/538 (0%)	0	1/560 (0.2%)	1
International normalised ratio abnormal	1/538 (0.2%)	1	0/560 (0%)	0
Kidney injury molecule-1	1/538 (0.2%)	1	1/560 (0.2%)	1
Methicillin-resistant staphylococcal aureus test positive	0/538 (0%)	0	1/560 (0.2%)	1
NIH stroke scale	1/538 (0.2%)	1	0/560 (0%)	0
NIH stroke scale score increased	0/538 (0%)	0	1/560 (0.2%)	1
Occult blood positive	0/538 (0%)	0	1/560 (0.2%)	2
Oxygen saturation	1/538 (0.2%)	1	0/560 (0%)	0
Oxygen saturation decreased	2/538 (0.4%)	2	1/560 (0.2%)	1
Pathology test	0/538 (0%)	0	1/560 (0.2%)	1
Radial pulse abnormal	0/538 (0%)	0	1/560 (0.2%)	1
Red blood cells urine positive	1/538 (0.2%)	1	0/560 (0%)	0
Sputum culture positive	1/538 (0.2%)	1	1/560 (0.2%)	1
Transaminases increased	1/538 (0.2%)	1	1/560 (0.2%)	1
Troponin I increased	2/538 (0.4%)	2	0/560 (0%)	0
Urine output decreased	15/538 (2.8%)	15	18/560 (3.2%)	18
White blood cell count increased	1/538 (0.2%)	1	1/560 (0.2%)	1
Metabolism and nutrition disorders
Acidosis	1/538 (0.2%)	1	0/560 (0%)	0
Feeding disorder	0/538 (0%)	0	1/560 (0.2%)	1
Fluid overload	1/538 (0.2%)	1	2/560 (0.4%)	2
Fluid retention	0/538 (0%)	0	1/560 (0.2%)	1
Hypercalcaemia	2/538 (0.4%)	2	7/560 (1.3%)	8
Hyperkalaemia	15/538 (2.8%)	15	15/560 (2.7%)	16
Hypernatraemia	0/538 (0%)	0	1/560 (0.2%)	1
Hyperphosphataemia	5/538 (0.9%)	5	6/560 (1.1%)	6
Hyperphosphatasaemia	1/538 (0.2%)	1	0/560 (0%)	0
Hypervolaemia	1/538 (0.2%)	1	1/560 (0.2%)	1
Hypocalcaemia	55/538 (10.2%)	56	46/560 (8.2%)	52
Hypoglycaemia	0/538 (0%)	0	1/560 (0.2%)	1
Hypokalaemia	0/538 (0%)	0	1/560 (0.2%)	1
Hyponatraemia	1/538 (0.2%)	1	1/560 (0.2%)	1
Hypophosphataemia	1/538 (0.2%)	1	0/560 (0%)	0
Hypovolaemia	1/538 (0.2%)	1	0/560 (0%)	0
Malnutrition	1/538 (0.2%)	1	0/560 (0%)	0
Metabolic acidosis	0/538 (0%)	0	1/560 (0.2%)	1
Metabolic alkalosis	0/538 (0%)	0	1/560 (0.2%)	1
Musculoskeletal and connective tissue disorders
Compartment syndrome	0/538 (0%)	0	1/560 (0.2%)	1
Hypercreatinaemia	1/538 (0.2%)	1	0/560 (0%)	0
Nervous system disorders
Altered state of consciousness	1/538 (0.2%)	1	0/560 (0%)	0
Anoxic encephalopathy	0/538 (0%)	0	2/560 (0.4%)	2
Aphasia	1/538 (0.2%)	1	0/560 (0%)	0
Atonic seizures	0/538 (0%)	0	1/560 (0.2%)	1
Brain stem stroke	0/538 (0%)	0	1/560 (0.2%)	1
Cerebellar infarction	1/538 (0.2%)	1	0/560 (0%)	0
Cerebral artery embolism	2/538 (0.4%)	2	0/560 (0%)	0
Cerebral infarction	0/538 (0%)	0	1/560 (0.2%)	1
Cerebral venous thrombosis	0/538 (0%)	0	1/560 (0.2%)	1
Cerebrovascular accident	1/538 (0.2%)	1	1/560 (0.2%)	1
Depressed level of consciousness	0/538 (0%)	0	1/560 (0.2%)	1
Embolic stroke	5/538 (0.9%)	5	3/560 (0.5%)	3
Encephalopathy	1/538 (0.2%)	1	1/560 (0.2%)	1
Essential tremor	1/538 (0.2%)	1	0/560 (0%)	0
Grand mal convulsion	0/538 (0%)	0	1/560 (0.2%)	1
Hemiparesis	0/538 (0%)	0	2/560 (0.4%)	2
Ischaemic stroke	5/538 (0.9%)	5	2/560 (0.4%)	2
Partial seizures	0/538 (0%)	0	1/560 (0.2%)	1
Seizure anoxic	0/538 (0%)	0	1/560 (0.2%)	1
Serotonin syndrome	1/538 (0.2%)	1	0/560 (0%)	0
Simple partial seizures	1/538 (0.2%)	1	0/560 (0%)	0
Stroke in evolution	0/538 (0%)	0	1/560 (0.2%)	1
Subarachnoid haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
Transient ischaemic attack	0/538 (0%)	0	1/560 (0.2%)	1
Psychiatric disorders
Adjustment disorder with depressed mood	0/538 (0%)	0	1/560 (0.2%)	1
Confusional state	1/538 (0.2%)	1	0/560 (0%)	0
Paranoia	0/538 (0%)	0	1/560 (0.2%)	1
Renal and urinary disorders
Acute prerenal failure	15/538 (2.8%)	16	14/560 (2.5%)	14
Anuria	1/538 (0.2%)	1	0/560 (0%)	0
Azotaemia	0/538 (0%)	0	1/560 (0.2%)	1
Haematuria	0/538 (0%)	0	1/560 (0.2%)	1
Haemoglobinuria	2/538 (0.4%)	2	2/560 (0.4%)	2
Oliguria	5/538 (0.9%)	5	3/560 (0.5%)	3
Renal disorder	1/538 (0.2%)	1	0/560 (0%)	0
Renal failure	2/538 (0.4%)	2	5/560 (0.9%)	5
Renal failure acute	8/538 (1.5%)	8	2/560 (0.4%)	2
Renal impairment	2/538 (0.4%)	2	3/560 (0.5%)	3
Renal mass	1/538 (0.2%)	1	0/560 (0%)	0
Renal tubular necrosis	0/538 (0%)	0	1/560 (0.2%)	1
Urinary bladder haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
Urinary retention	3/538 (0.6%)	3	5/560 (0.9%)	5
Reproductive system and breast disorders
Bleeding anovulatory	0/538 (0%)	0	1/560 (0.2%)	1
Scrotal swelling	0/538 (0%)	0	1/560 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute interstitial pneumonitis	3/538 (0.6%)	3	1/560 (0.2%)	1
Acute lung injury	1/538 (0.2%)	1	0/560 (0%)	0
Acute pulmonary oedema	1/538 (0.2%)	1	1/560 (0.2%)	1
Acute respiratory distress syndrome	4/538 (0.7%)	4	5/560 (0.9%)	5
Acute respiratory failure	9/538 (1.7%)	10	11/560 (2%)	11
Anaemic hypoxia	3/538 (0.6%)	3	6/560 (1.1%)	6
Apnoeic attack	0/538 (0%)	0	1/560 (0.2%)	1
Aspiration	2/538 (0.4%)	2	0/560 (0%)	0
Atelectasis	1/538 (0.2%)	1	0/560 (0%)	0
Clotted haemothorax	0/538 (0%)	0	1/560 (0.2%)	1
Cough	3/538 (0.6%)	3	5/560 (0.9%)	5
Dyspnoea	27/538 (5%)	28	24/560 (4.3%)	25
Dyspnoea at rest	8/538 (1.5%)	9	12/560 (2.1%)	12
Dyspnoea exertional	6/538 (1.1%)	6	6/560 (1.1%)	6
Epistaxis	0/538 (0%)	0	1/560 (0.2%)	1
Haemothorax	0/538 (0%)	0	1/560 (0.2%)	1
Hypercapnia	1/538 (0.2%)	1	0/560 (0%)	0
Hypoxia	33/538 (6.1%)	36	39/560 (7%)	39
Idiopathic pneumonia syndrome	1/538 (0.2%)	1	0/560 (0%)	0
Lung consolidation	0/538 (0%)	0	1/560 (0.2%)	1
Mediastinal disorder	0/538 (0%)	0	1/560 (0.2%)	1
Mediastinal haematoma	1/538 (0.2%)	1	0/560 (0%)	0
Mediastinal haemorrhage	6/538 (1.1%)	6	6/560 (1.1%)	6
Pleural effusion	11/538 (2%)	13	9/560 (1.6%)	9
Pneumothorax	3/538 (0.6%)	3	0/560 (0%)	0
Pneumothorax spontaneous tension	0/538 (0%)	0	1/560 (0.2%)	1
Pulmonary embolism	1/538 (0.2%)	1	1/560 (0.2%)	1
Respiratory acidosis	1/538 (0.2%)	1	0/560 (0%)	0
Respiratory distress	1/538 (0.2%)	1	0/560 (0%)	0
Respiratory failure	2/538 (0.4%)	3	1/560 (0.2%)	1
Stridor	0/538 (0%)	0	1/560 (0.2%)	1
Tachypnoea	1/538 (0.2%)	1	2/560 (0.4%)	2
Thoracic haemorrhage	1/538 (0.2%)	1	0/560 (0%)	0
Vocal cord disorder	1/538 (0.2%)	1	0/560 (0%)	0
Wheezing	6/538 (1.1%)	7	12/560 (2.1%)	12
Skin and subcutaneous tissue disorders
Angioedema	1/538 (0.2%)	1	0/560 (0%)	0
Itching scar	1/538 (0.2%)	1	0/560 (0%)	0
Pruritus allergic	0/538 (0%)	0	1/560 (0.2%)	1
Skin ulcer	0/538 (0%)	0	1/560 (0.2%)	1
Surgical and medical procedures
Abdominal exploration	1/538 (0.2%)	1	0/560 (0%)	0
Allergy prophylaxis	0/538 (0%)	0	1/560 (0.2%)	1
Aneurysm repair	1/538 (0.2%)	1	0/560 (0%)	0
Cardiac pacemaker insertion	1/538 (0.2%)	1	1/560 (0.2%)	1
Dialysis	0/538 (0%)	0	1/560 (0.2%)	1
Extracorporeal membrane oxygenation	0/538 (0%)	0	1/560 (0.2%)	1
Hypotensive anaesthesia procedure	3/538 (0.6%)	3	2/560 (0.4%)	2
Incisional drainage	2/538 (0.4%)	2	2/560 (0.4%)	2
Intracerebral haematoma evacuation	0/538 (0%)	0	1/560 (0.2%)	1
Pericardial drainage	1/538 (0.2%)	1	0/560 (0%)	0
Removal of foreign body	1/538 (0.2%)	1	0/560 (0%)	0
Tracheostomy	0/538 (0%)	0	1/560 (0.2%)	2
Vascular disorders
Accelerated hypertension	2/538 (0.4%)	2	1/560 (0.2%)	1
Aortic intramural haematoma	0/538 (0%)	0	1/560 (0.2%)	1
Arterial thrombosis	0/538 (0%)	0	1/560 (0.2%)	1
Arteriovenous fistula	1/538 (0.2%)	1	0/560 (0%)	0
Deep vein thrombosis	0/538 (0%)	0	1/560 (0.2%)	1
Diastolic hypertension	0/538 (0%)	0	2/560 (0.4%)	2
Diastolic hypotension	14/538 (2.6%)	14	14/560 (2.5%)	14
Essential hypertension	5/538 (0.9%)	5	3/560 (0.5%)	3
Haematoma	1/538 (0.2%)	1	0/560 (0%)	0
Haemodynamic instability	1/538 (0.2%)	1	0/560 (0%)	0
Haemorrhage	0/538 (0%)	0	1/560 (0.2%)	1
Hypertension	13/538 (2.4%)	14	13/560 (2.3%)	13
Hypotension	97/538 (18%)	106	87/560 (15.5%)	96
Hypovolaemic shock	0/538 (0%)	0	2/560 (0.4%)	2
Ischaemic limb pain	0/538 (0%)	0	1/560 (0.2%)	1
Labile hypertension	1/538 (0.2%)	1	1/560 (0.2%)	1
Orthostatic hypotension	2/538 (0.4%)	2	0/560 (0%)	0
Peripheral vascular disorder	0/538 (0%)	0	1/560 (0.2%)	1
Poor peripheral circulation	1/538 (0.2%)	1	0/560 (0%)	0
Venous thrombosis limb	1/538 (0.2%)	1	0/560 (0%)	0
Other (Not Including Serious) Adverse Events
	Shorter-storage Red Blood Cell Units		Longer-storage Red Blood Cell Units
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	324/538 (60.2%)		334/560 (59.6%)
Blood and lymphatic system disorders
Haemolysis	2/538 (0.4%)	2	0/560 (0%)	0
Leukocytosis	7/538 (1.3%)	7	4/560 (0.7%)	4
Cardiac disorders
Accessory cardiac pathway	0/538 (0%)	0	1/560 (0.2%)	1
Acute myocardial infarction	3/538 (0.6%)	3	2/560 (0.4%)	2
Arrhythmia	1/538 (0.2%)	1	1/560 (0.2%)	1
Atrial fibrillation	1/538 (0.2%)	1	0/560 (0%)	0
Atrial tachycardia	1/538 (0.2%)	1	0/560 (0%)	0
Bradyarrhythmia	1/538 (0.2%)	1	1/560 (0.2%)	1
Bradycardia	4/538 (0.7%)	4	10/560 (1.8%)	10
Cardiac failure congestive	1/538 (0.2%)	1	0/560 (0%)	0
Myocardial infarction	2/538 (0.4%)	2	1/560 (0.2%)	1
Myocardial ischaemia	2/538 (0.4%)	2	2/560 (0.4%)	2
Sinus bradycardia	12/538 (2.2%)	12	11/560 (2%)	12
Sinus tachycardia	25/538 (4.6%)	27	28/560 (5%)	28
Supraventricular tachyarrhythmia	0/538 (0%)	0	1/560 (0.2%)	1
Supraventricular tachycardia	0/538 (0%)	0	1/560 (0.2%)	1
Tachycardia	1/538 (0.2%)	1	1/560 (0.2%)	1
Ventricular tachyarrhythmia	3/538 (0.6%)	3	0/560 (0%)	0
Ventricular tachycardia	7/538 (1.3%)	7	3/560 (0.5%)	3
Congenital, familial and genetic disorders
Familial hypocalciuric hypercalcaemia	4/538 (0.7%)	4	2/560 (0.4%)	2
General disorders
Adverse reaction	0/538 (0%)	0	1/560 (0.2%)	1
Catheter site phlebitis	0/538 (0%)	0	1/560 (0.2%)	1
Chest pain	0/538 (0%)	0	1/560 (0.2%)	1
Chills	1/538 (0.2%)	1	0/560 (0%)	0
Hyperthermia	1/538 (0.2%)	1	0/560 (0%)	0
Oedema peripheral	1/538 (0.2%)	1	0/560 (0%)	0
Pyrexia	1/538 (0.2%)	1	0/560 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	78/538 (14.5%)	89	98/560 (17.5%)	107
Hyperbilirubinaemia neonatal	0/538 (0%)	0	1/560 (0.2%)	1
Immune system disorders
Alloimmunisation	1/538 (0.2%)	1	0/560 (0%)	0
Hypersensitivity	1/538 (0.2%)	1	0/560 (0%)	0
Infections and infestations
Acinetobacter infection	0/538 (0%)	0	1/560 (0.2%)	1
Actinomycotic pulmonary infection	1/538 (0.2%)	1	0/560 (0%)	0
Acute sinusitis	0/538 (0%)	0	1/560 (0.2%)	1
Adenoviral upper respiratory infection	1/538 (0.2%)	1	1/560 (0.2%)	1
Application site cellulitis	2/538 (0.4%)	2	0/560 (0%)	0
Arteriovenous graft site infection	0/538 (0%)	0	1/560 (0.2%)	1
Aspergillosis oral	1/538 (0.2%)	1	0/560 (0%)	0
Asymptomatic bacteriuria	1/538 (0.2%)	1	0/560 (0%)	0
Bacteriuria	1/538 (0.2%)	1	0/560 (0%)	0
Bronchopneumonia	2/538 (0.4%)	2	2/560 (0.4%)	2
Catheter site cellulitis	0/538 (0%)	0	1/560 (0.2%)	1
Clostridium difficile colitis	0/538 (0%)	0	1/560 (0.2%)	1
Cytomegalovirus urinary tract infection	1/538 (0.2%)	1	0/560 (0%)	0
Enterobacter tracheobronchitis	0/538 (0%)	0	1/560 (0.2%)	1
Escherichia urinary tract infection	1/538 (0.2%)	1	3/560 (0.5%)	3
Genitourinary tract infection	10/538 (1.9%)	10	9/560 (1.6%)	10
Incision site infection	0/538 (0%)	0	1/560 (0.2%)	1
Influenza	0/538 (0%)	0	1/560 (0.2%)	1
Klebsiella bacteraemia	1/538 (0.2%)	1	0/560 (0%)	0
Parotitis	1/538 (0.2%)	1	0/560 (0%)	0
Upper respiratory fungal infection	0/538 (0%)	0	1/560 (0.2%)	1
Urinary tract infection	2/538 (0.4%)	2	0/560 (0%)	0
Urinary tract infection bacterial	1/538 (0.2%)	1	2/560 (0.4%)	2
Wound infection	1/538 (0.2%)	1	0/560 (0%)	0
Injury, poisoning and procedural complications
Allergic transfusion reaction	0/538 (0%)	0	2/560 (0.4%)	2
Iatrogenic injury	2/538 (0.4%)	2	2/560 (0.4%)	2
Post procedural haematuria	0/538 (0%)	0	2/560 (0.4%)	2
Postoperative renal failure	1/538 (0.2%)	1	0/560 (0%)	0
Procedural hypotension	3/538 (0.6%)	3	2/560 (0.4%)	2
Urethral stricture traumatic	0/538 (0%)	0	1/560 (0.2%)	1
Urinary retention postoperative	7/538 (1.3%)	7	10/560 (1.8%)	10
Investigations
Bacteria blood identified	0/538 (0%)	0	1/560 (0.2%)	1
Bacteria sputum identified	2/538 (0.4%)	2	1/560 (0.2%)	1
Bacteria urine	1/538 (0.2%)	1	0/560 (0%)	0
Bilirubin conjugated abnormal	1/538 (0.2%)	1	0/560 (0%)	0
Bilirubin conjugated increased	0/538 (0%)	0	2/560 (0.4%)	2
Blood pressure abnormal	0/538 (0%)	0	1/560 (0.2%)	1
Blood pressure decreased	5/538 (0.9%)	5	3/560 (0.5%)	3
Blood pressure orthostatic decreased	1/538 (0.2%)	1	0/560 (0%)	0
Blood urine	0/538 (0%)	0	1/560 (0.2%)	1
Body temperature increased	8/538 (1.5%)	8	3/560 (0.5%)	3
Cardiac enzymes increased	7/538 (1.3%)	7	9/560 (1.6%)	9
Differential white blood cell count normal	0/538 (0%)	0	1/560 (0.2%)	1
ECG signs of myocardial ischaemia	7/538 (1.3%)	7	8/560 (1.4%)	8
Heart rate decreased	1/538 (0.2%)	1	0/560 (0%)	0
Methicillin-resistant staphylococcal aureus test positive	1/538 (0.2%)	1	0/560 (0%)	0
Oxygen saturation decreased	1/538 (0.2%)	1	0/560 (0%)	0
Sputum culture	1/538 (0.2%)	1	0/560 (0%)	0
Sputum culture positive	2/538 (0.4%)	3	0/560 (0%)	0
Troponin	1/538 (0.2%)	1	0/560 (0%)	0
Urine output decreased	3/538 (0.6%)	3	1/560 (0.2%)	1
Metabolism and nutrition disorders
Fluid overload	1/538 (0.2%)	1	0/560 (0%)	0
Fluid retention	0/538 (0%)	0	1/560 (0.2%)	1
Hypercalcaemia	2/538 (0.4%)	2	2/560 (0.4%)	2
Hyperkalaemia	18/538 (3.3%)	18	18/560 (3.2%)	18
Hyperphosphataemia	25/538 (4.6%)	30	11/560 (2%)	13
Hyperphosphatasaemia	1/538 (0.2%)	1	3/560 (0.5%)	3
Hypocalcaemia	187/538 (34.8%)	230	191/560 (34.1%)	228
Hyponatraemia	0/538 (0%)	0	1/560 (0.2%)	1
Hypophosphataemia	0/538 (0%)	0	2/560 (0.4%)	2
Nervous system disorders
Aphasia	0/538 (0%)	0	1/560 (0.2%)	1
Embolic stroke	0/538 (0%)	0	1/560 (0.2%)	1
Haemorrhagic stroke	0/538 (0%)	0	1/560 (0.2%)	1
Renal and urinary disorders
Acute prerenal failure	8/538 (1.5%)	8	5/560 (0.9%)	7
Haematuria	1/538 (0.2%)	1	1/560 (0.2%)	1
Haemoglobinuria	2/538 (0.4%)	2	1/560 (0.2%)	1
Hypocalciuria	3/538 (0.6%)	4	0/560 (0%)	0
Oliguria	2/538 (0.4%)	2	4/560 (0.7%)	4
Renal failure	0/538 (0%)	0	2/560 (0.4%)	2
Renal failure acute	2/538 (0.4%)	2	1/560 (0.2%)	1
Renal impairment	2/538 (0.4%)	2	2/560 (0.4%)	3
Renal tubular necrosis	0/538 (0%)	0	1/560 (0.2%)	1
Urinary incontinence	2/538 (0.4%)	2	2/560 (0.4%)	2
Urinary retention	5/538 (0.9%)	5	3/560 (0.5%)	3
Urine flow decreased	1/538 (0.2%)	1	0/560 (0%)	0
Reproductive system and breast disorders
Scrotal oedema	1/538 (0.2%)	1	0/560 (0%)	0
Respiratory, thoracic and mediastinal disorders
Anaemic hypoxia	1/538 (0.2%)	1	2/560 (0.4%)	2
Bradypnoea	1/538 (0.2%)	1	0/560 (0%)	0
Cough	3/538 (0.6%)	3	2/560 (0.4%)	2
Dyspnoea	10/538 (1.9%)	11	11/560 (2%)	11
Dyspnoea at rest	3/538 (0.6%)	3	4/560 (0.7%)	4
Dyspnoea exertional	15/538 (2.8%)	16	20/560 (3.6%)	20
Hypoxia	8/538 (1.5%)	8	14/560 (2.5%)	14
Pleural effusion	1/538 (0.2%)	1	0/560 (0%)	0
Productive cough	3/538 (0.6%)	3	3/560 (0.5%)	3
Pulmonary embolism	1/538 (0.2%)	1	0/560 (0%)	0
Tachypnoea	1/538 (0.2%)	1	0/560 (0%)	0
Wheezing	16/538 (3%)	17	12/560 (2.1%)	12
Skin and subcutaneous tissue disorders
Erythema	2/538 (0.4%)	2	1/560 (0.2%)	1
Surgical and medical procedures
Haemophilus influenzae type b immunisation	0/538 (0%)	0	1/560 (0.2%)	1
Hypotensive anaesthesia procedure	1/538 (0.2%)	1	1/560 (0.2%)	1
Vascular disorders
Accelerated hypertension	4/538 (0.7%)	4	5/560 (0.9%)	5
Diastolic hypertension	2/538 (0.4%)	3	1/560 (0.2%)	1
Diastolic hypotension	6/538 (1.1%)	6	4/560 (0.7%)	4
Essential hypertension	1/538 (0.2%)	1	2/560 (0.4%)	2
Hypertension	20/538 (3.7%)	20	21/560 (3.8%)	23
Hypertensive crisis	1/538 (0.2%)	1	0/560 (0%)	0
Hypotension	71/538 (13.2%)	76	73/560 (13%)	76
Orthostatic hypotension	0/538 (0%)	0	1/560 (0.2%)	1
Thrombophlebitis	1/538 (0.2%)	1	0/560 (0%)	0

Limitations/Caveats

Only 4 pediatric subjects were enrolled. One treatment arm had only one subject with available data for analyzing the change in ALT outcome. Therefore, to protect patient confidentiality, results were not entered for this outcome.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.