Red Cell Storage Duration Study (RECESS)

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Erythrocyte Transfusion
• Intervention / Treatment: Biological: Red blood cell units stored <= 10 days; Biological: Red blood cell units stored >= 21 days

• Study Type: Interventional
• Enrollment (Actual): 1481
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Fort Wayne, Indiana, United States, 46802
      • St. Joseph Hospital
    • Fort Wayne, Indiana, United States, 46804
      • Indiana/Ohio Heart
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women'S Hospital
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02116
      • St. Elizabeth's Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Fairview Southdale Hospital/University of Minnesota Medical Center Fairview
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson Medical School
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Deaconess Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Health Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical School
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
    • Durham, North Carolina, United States, 27713
      • Duke University
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Heart Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15219
      • UPMC-Mercy Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Presbyterian and Shadyside
  • Tennessee
    • Nashville, Tennessee, United States, 37323
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Houston, Texas, United States, 77030
      • Texas Heart Institute
  • Washington
    • Seattle, Washington, United States, 98108
      • Veterans Administration Puget Sound
    • Seattle, Washington, United States, 98195
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
      • Froedtert Memorial Lutheran Hospital
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Lukes Medical Center
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Vascular Heart Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	Through post-operative day 7, hospital discharge, or death, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality	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.	28 days post-surgery
Change in Multiple Organ Dysfunction Score From Pre-operative Baseline.	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).	Through 28 days post-surgery, hospital discharge, or death, whichever occurs first
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
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
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
Ventilation Duration	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.	Through post-operative day 28, hospital discharge, or death, whichever occurs first
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
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
Change in Lactate From Pre-operative Value to Worst Post-operative Value	The arterial lactate levels were adjusted to make them comparable to venous lactate levels.	Through post-operative day 7, hospital discharge, or death, whichever occurs first
Change in Bilirubin From Pre-operative Value to Worst Post-operative Value		Through post-operative day 7, hospital discharge, or death, whichever occurs first
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
Days to First Bowel Movement	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.	Through post-operative day 28, hospital discharge, or death, whichever occurs first
Days to First Solid Food	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.	Through post-operative day 28, hospital discharge, or death, whichever occurs first
Days Alive and Ventilator Free Through Post-op Day 28		Through post-op day 28
Any Mechanical Ventilation More Than 48 Hours Post-operation		48 hours post-operation through day 28, hospital discharge, or death, whichever occurs first

Collaborators and Investigators

• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Thomas Ortel, MD, Duke University; Principal Investigator: Paul Ness, MD, Johns Hopkins University; Principal Investigator: James George, MD, University of Oklahoma; Principal Investigator: James Bussel, MD, Weill Medical College of Cornell University; Principal Investigator: Richard Kaufman, MD, Brigham and Women's Hospital; Principal Investigator: Steven Sloan, MD, Boston Children's Hospital; 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: Rhonda Cooke, MD, University of Maryland; 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: 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

Publications and helpful links

General Publications

• Kekre N, Mallick R, Allan D, Tinmouth A, Tay J. The impact of prolonged storage of red blood cells on cancer survival. PLoS One. 2013 Jul 16;8(7):e68820. doi: 10.1371/journal.pone.0068820. Print 2013.
• Delaney M, Stark PC, Suh M, Triulzi DJ, Hess JR, Steiner ME, Stowell CP, Sloan SR. Massive Transfusion in Cardiac Surgery: The Impact of Blood Component Ratios on Clinical Outcomes and Survival. Anesth Analg. 2017 Jun;124(6):1777-1782. doi: 10.1213/ANE.0000000000001926.
• Steiner ME, Ness PM, Assmann SF, Triulzi DJ, Sloan SR, Delaney M, Granger S, Bennett-Guerrero E, Blajchman MA, Scavo V, Carson JL, Levy JH, Whitman G, D'Andrea P, Pulkrabek S, Ortel TL, Bornikova L, Raife T, Puca KE, Kaufman RM, Nuttall GA, Young PP, Youssef S, Engelman R, Greilich PE, Miles R, Josephson CD, Bracey A, Cooke R, McCullough J, Hunsaker R, Uhl L, McFarland JG, Park Y, Cushing MM, Klodell CT, Karanam R, Roberts PR, Dyke C, Hod EA, Stowell CP. Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med. 2015 Apr 9;372(15):1419-29. doi: 10.1056/NEJMoa1414219.
• Berra L, Coppadoro A, Yu B, Lei C, Spagnolli E, Steinbicker AU, Bloch KD, Lin T, Sammy FY, Warren HS, Fernandez BO, Feelisch M, Dzik WH, Stowell CP, Zapol WM. Transfusion of stored autologous blood does not alter reactive hyperemia index in healthy volunteers. Anesthesiology. 2012 Jul;117(1):56-63. doi: 10.1097/ALN.0b013e31825575e6.
• Steiner ME, Assmann SF, Levy JH, Marshall J, Pulkrabek S, Sloan SR, Triulzi D, Stowell CP. Addressing the question of the effect of RBC storage on clinical outcomes: the Red Cell Storage Duration Study (RECESS) (Section 7). Transfus Apher Sci. 2010 Aug;43(1):107-16. doi: 10.1016/j.transci.2010.05.014. Epub 2010 Jul 23.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: October 7, 2009
• First Submitted That Met QC Criteria: October 7, 2009
• First Posted (Estimate): October 8, 2009

Study Record Updates

• Last Update Posted (Estimate): June 9, 2015
• Last Update Submitted That Met QC Criteria: May 22, 2015
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Cardiac surgery; Transfusion; Red blood cell
• Other Study ID Numbers: 676; U01HL072268 (U.S. NIH Grant/Contract); HL072268; HL072033; HL072291; HL072196; HL072289; HL072248; HL072191; HL072299; HL072305; HL072274; HL072028; HL072359; HL072072; HL072355; HL072283; HL072346; HL072331; HL072290