Mechanism and Repository Study for the Red Cell Storage Duration Study

NCT ID: NCT01541319

Last Updated: 2016-09-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 92 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2016-08-31

Brief Summary

A large multicenter randomized controlled trial of approximately 1700 critically ill patients' status post complex cardiac surgery with sternotomy, called the Red Cell Storage Duration Study (RECESS), is currently ongoing. In the RECESS trial, study groups are randomized to either RBCs of less than or equal to 10 days storage time or to greater than or equal to 21 days. The primary outcome of RECESS is a change in multiple organ dysfunction score. Secondary outcomes in RECESS include all cause 28-day mortality, mechanical ventilation free days, and other clinical outcomes. The RECESS study presents a unique opportunity to investigate mechanisms associated with RBC storage duration in the context of clinical outcomes for well-characterized surgical study groups. The ancillary study described here is called the Mechanism and Repository Study (MARS) for RECESS.

The MARS study will analyze the most commonly reported and hypothesized mechanisms considered to be associated with the RBC storage lesion and adverse outcomes in critically ill patients. Laboratories with expertise in RBC function, nitric oxide mechanisms, the coagulation cascade, microparticle analysis and immunology will each examine hypotheses addressing mechanisms potentially able to relate storage time to clinical outcomes in RBC transfusion recipients. At the conclusion of the study, the results will provide a much better understanding of how RBC storage age affects recipient RBC function, coagulation parameters, microparticle load and immune modulation. Perhaps most importantly, this study will also develop a large sample repository for future analysis.

Detailed Description

MARS will enroll approximately 250 of the subjects participating in the RECESS study, and an additional 50 healthy volunteers. The RECESS subjects participating in MARS will have blood drawn before their cardiac surgery, and again 2 days after their cardiac surgery. If they have received any red blood cell (RBC) transfusions during their surgery or in the 96 hours following the end of their surgery, they will also have blood drawn at approximately 6 days, 28 days, and 180 days after their surgery, and will answer a health questionnaire at the 28-day and 180-day visits. The healthy volunteers participating in MARS will each have a single blood draw.

All MARS subjects will have blood samples sent to a repository for future study. A subset of the RECESS subjects participating in MARS, and all the healthy volunteers participating in MARS, will also have a number of laboratory tests performed as part of the MARS study. These tests will include

1. laboratory measures of vascular signaling, including NO content, NO disposition; oxidative modification to RBC membrane thiols; and the flux in vasoactive S-nitrosothiols (RSNOs).

2. laboratory measures of coagulation, including thrombin generation; prothrombin fragment 1+2, fibrinopeptide A; soluble thrombomodulin, protein C, PAI-1, tissue plasminogen activator, Factor V, Factor VII, Factor VIII, D-Dimer, antithrombin III, soluble endothelial protein C receptor, TFPI, Xia, INR, PT, and PTT (all using standard testing methods); and clot formation measured by rotation thrombo-elastometry.

3. laboratory measures of microparticle counts, including CD3(T cells), CD66b(Granulocytes), CD 14(Monocytes), CD42a(Platelets), CD235a(RBCs), CD41a(Platelets), CD44(Surface glycoprotein), CD35(Complement receptor1), CD108(Semaphorin 7A), Annexin V, CD154(CD40-ligand), CD62p(p-selectin), CD59(Protectin), CD55(complement DAF), CD58(LFA-3).

4. laboratory measures of inflammation and immune function, including regulatory T cells,Th17 cells, MMP-9, MPO, Pi-1 (total), sE-Selectin, sICAM-1, sVCAM-1, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IFN-γ, GM-CSF, and TNF-α.

At one hospital, samples from RBC units transfused to MARS subjects will also be analyzed for nitric oxide parameters.

The primary objective of MARS is to compare post-operative values of these laboratory parameters between RBC-transfused RECESS subjects randomized to receive RBCs stored 10 days or less and RBC-transfused RECESS subjects randomized to receive RBCs stored 21 days or more.

Secondary objectives include

1. Determining whether values of the above laboratory parameters are associated with clinical outcomes among RECESS participants, including change in the multi-organ dysfunction score (MODS) from pre-surgery through death, hospital discharge, or post-operative day 7 (whichever occurs first); change in the MODS from pre-surgery through death, hospital discharge, or post-operative day 28 (whichever occurs first); and all-cause mortality.

2. Determining whether there are correlations between the above laboratory parameters in RECESS subjects at each time point (pre-surgery and post-operative days 2, 6, and 180).

3. Comparing changes in the above laboratory parameters from pre-surgery through Day 2 for randomized RECESS subjects who undergo surgery but do not receive any RBC transfusions versus those in each randomized treatment group who do receive RBC transfusions.

4. Comparing values of the above laboratory parameters in healthy volunteers to pre-surgery values in RECESS subjects scheduled to undergo cardiac surgery.

5. Assessing how nitric oxide parameters in RBC units differ depending on storage duration of the units.

6. Assessing how post-transfusion nitric oxide parameters in transfused subjects differ depending on the pre-transfusion nitric oxide parameters and the parameters in the transfused units.

Conditions

Cardiac Surgery; Erythrocyte Transfusion

Study Design

• Study Time Perspective: PROSPECTIVE

Study Groups

Randomized to <= 10day RBCs & transfused

Subjects in the RECESS study who were randomized to receive red blood cell (RBC) units stored no more than 10 days, and who received at least one RBC transfusion between randomization and 96 hours after the cardiac surgery ends

No interventions assigned to this group

Randomized to >= 21day RBCs & transfused

Subjects in the RECESS study who were randomized to receive red blood cell (RBC) units stored at least 21 days, and who received at least one RBC transfusion between randomization and 96 hours after the cardiac surgery ends

No interventions assigned to this group

Randomized but not transfused

Subjects randomized in the RECESS study who did not receive any red blood cell units between randomization and 96 hours after the end of surgery

No interventions assigned to this group

Healthy volunteers

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Randomized in Red Cell Storage Duration Study (RECESS)

2. Patients ≥ 18 years old

1. At least 18 years old

2. In generally good health

Exclusion Criteria

1. History of red blood cell transfusion within the previous 6 months.

2. History of surgery within the previous 6 months.

3. Currently treated with inhaled nitric oxide, nitroglycerin in any form, or nitroprusside.

4. Currently treated with prednisone, corticosteroids, cyclosporine, chemotherapy, remicade, methotrexate, Enbrel and/or any antibody based therapy to modulate the immune system.

5. Currently treated with heparin or other anticoagulants (for example coumadin, pradaxa, and low molecular weight heparin).

6. Received any non-steroidal anti-inflammatory drug within the previous 24 hours.

7. Received aspirin within the previous 5 days.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Carelon Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip Spinella, MD

Role: STUDY_CHAIR

Washington University School of Medicine

Philip Norris, MD

Role: STUDY_CHAIR

Vitalant Research Institute

Susan Assmann, PhD

Role: PRINCIPAL_INVESTIGATOR

Carelon Research

Locations

Blood Systems Research Institute

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

Indiana/Ohio Heart

Fort Wayne, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

St. Elizabeth's Medical Center

Boston, Massachusetts, United States

University of Minnesota - Fairview

Minneapolis, Minnesota, United States

Robert Wood Johnson Medial School

New Brunswick, New Jersey, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern

Dallas, Texas, United States

Texas Heart Institute

Houston, Texas, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Froedtert Memorial Hospital

Milwaukee, Wisconsin, United States

Aspirus Heart & Vascular Institute

Wausau, Wisconsin, United States

Countries

United States

Other Identifiers

3U01HL072268-09S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

712

Identifier Type: -

Identifier Source: org_study_id