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Microparticles in Stored RBC as Potential Mediators of Transfusion Complications

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Miami
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Wenche Jy, University of Miami
ClinicalTrials.gov Identifier:
NCT01185600
First received: August 17, 2010
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

INTRODUCTION. Cell-derived microparticles (MP) are released in cell activation, apoptosis and other processes. MP derived from red cells (RMP) are known to be released from stored packed red blood cells (PRBC), and their number increases with storage time. This constitutes one aspect of the storage lesion. Adverse transfusion events are known to increase with time of PRBC storage. The explanation for this is not known.

HYPOTHESIS. Based on their findings and those of others, the investigators propose to test the hypothesis that MP in stored PRBC contribute to adverse effects of transfusion. Specifically, MP in stored blood: (1) increase procoagulant activity, expression of pro-inflammatory mediators, immune suppression, and endothelial disturbance; and (2) increase the risk of transfusion and post-operative complications in patients undergoing coronary artery bypass grafting (CABG).

AIMS & PROCEDURES. The aim of this study is to assess the clinical significance of MPs in PRBC-related transfusion complications utilizing washed PRBC. Packed red blood cells (PRBC) will be washed at the blood bank to obtain MP depleted PRBC (PRBC-MP). A total of 500 patients undergoing CABG will be initially randomized to 2 groups: one to receive PRBC-MP, and the other conventional PRBC (PRBC+MP). Using a panel of lab tests/biomarkers selected for high sensitivity the investigators will compare the 2 groups with respect to subclinical physiologic host responses including (i) endothelial disturbances, (ii) inflammatory, and (iii) procoagulant responses. In addition, clinically evident transfusion complications and short term (<=30 days) surgical complications will be assessed and compared. Patients who are randomized but end up not requiring transfusion at surgery will serve as controls. Laboratory and clinical results will also be evaluated to elucidate which tests are significantly associated with clinically adverse effects.

SIGNIFICANCE. This study will shed new light on the biochemical and clinical effects of transfusion of MP. The findings of this investigation could significantly improve transfusion practice and safety.


Condition Intervention
Coronary Artery Bypass Graft Surgery
Biological: Washed RBC
Biological: Unwashed RBC

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Microparticles in Stored Red Blood Cells (RBC) as Potential Mediators of Transfusion Complications (II): Clinical Study

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • cell-derived microparticles [ Time Frame: one hour before surgery ] [ Designated as safety issue: Yes ]

    Cell-derived microparticles are a group of biomarkers used for evaluating the host biochemical physiological responses including (1) endothelial dysfunction, (2)procoagulant/prothrombotic activities, and (3) proinflammatory activities.

    Blood samples will be collected one hour before surgery for the measurement of cell-derived microparticles. The outcome of the measurement will be compared between arm 1 (washed RBC) and arm 2 (unwashed RBC).


  • Cell-derived microparticles [ Time Frame: one hour after surgery ] [ Designated as safety issue: Yes ]
    Blood samples will be collected one hour after surgery for the measurement of cell-derived microparticles. The outcome of the measurement will be compared between arm 1 (washed RBC) and arm 2 (unwashed RBC).

  • cell-derived microparticles [ Time Frame: one day after surgery ] [ Designated as safety issue: Yes ]
    Blood samples will be collected one day after surgery for the measurement of cell-derived microparticles. The outcome of the measurement will be compared between arm 1 (washed RBC) and arm 2 (unwashed RBC).

  • cell-derived microparticles [ Time Frame: 7 days after surgery ] [ Designated as safety issue: Yes ]
    Blood samples will be collected 7 days after surgery for the measurement of cell-derived microparticles. The outcome of the measurement will be compared between arm 1 (washed RBC) and arm 2 (unwashed RBC).


Secondary Outcome Measures:
  • Transfusion-related adverse events [ Time Frame: within one year after surgery ] [ Designated as safety issue: Yes ]
    The major transfusion-related events include (1) allergic reactions, (2) hemolysis, (3) anaphylactic shock, (4)sepsis, (5) transfusion related acute lung injury,(6)death, and (7)miscellaneous: coronary artery diseases, thrombosis, bleeding, CNS dysfunction, stroke, renal failure, bleeding.


Estimated Enrollment: 500
Study Start Date: July 2010
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Transfusion with washed RBC
Subject assigned to this arm will be transfused with washed RBC
Biological: Washed RBC
There is no pre-set dosage, frequency and duration for transfusion with washed RBC. It all depends on the conditions of patients during and after surgery. As circumstances arise, the physician will request needed washed RBC for the subject.
Other Name: Washed packed cells
Active Comparator: Transfusion with unwashed RBC
Subjects assigned to this arm will be transfused with unwashed RBC
Biological: Unwashed RBC
There is no pre-set dosage, frequency and duration for transfusion with unwashed RBC. It all depends on the conditions of patients during and after surgery. As circumstances arise, the physician will request needed unwashed RBC for the subject.
Other Name: Unwashed packed cells

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients requiring coronary artery bypass (CABG) surgery will be enrolled into the study if they: (1) are willing and able to give informed consent and to adhere to study follow up requirements; and (2) do not satisfy any of the exclusion criteria

Exclusion Criteria:

  • Patients will be ineligible for the study if they (1) are unable or unwilling to give informed consent; (2) are unable or unwilling to follow the study protocol; (3) are less than 21 years of age; (4) require emergency procedures; (5) require cardiopulmonary bypass (pump) during the operation; (6) require other surgical procedures in addition to coronary artery bypass; (7) have a proven coagulation or platelet disorder; (8) are unwilling to receive blood transfusions; (9) are pregnant; or (10) have cognitive impairment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185600

Contacts
Contact: John Morgan, MD 305-243-5308 jmorgan1@med.miami.edu
Contact: Orlando Gomez-Marin, PhD 305-243-6863 ogomez@med.miami.edu

Locations
United States, Florida
Jackson Memorial Hospital Recruiting
Miami, Florida, United States, 33136
Contact: Eve Sakran, MS    305-585-7226 ext 1    esakran@jhsmiami.org   
Principal Investigator: Wenche Jy, PhD         
Sub-Investigator: Marco Ricci, MD         
Sub-Investigator: Sherry Shariatmadar, MD         
Sub-Investigator: Yeon S Ahn, MD         
Sub-Investigator: Orlando Gomez-Marin, PhD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Wenche Jy, PhD University of Miami
  More Information

Publications:
Responsible Party: Wenche Jy, Research Associate Professor, University of Miami
ClinicalTrials.gov Identifier: NCT01185600     History of Changes
Other Study ID Numbers: 20090685, R01HL098031
Study First Received: August 17, 2010
Last Updated: March 6, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of Miami:
transfusion complications
washed RBC
microparticles
storage lesion

ClinicalTrials.gov processed this record on November 20, 2014