Microparticles in Stored Red Blood Cells (RBC) as Potential Mediators of Transfusion Complications (II): Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 177
- 试验地点
- 2
- 主要终点
- In Hospital Mortality
研究概览
简要总结
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.
详细描述
- Study Design.
1.1. Patient population. More than 500 coronary artery bypass surgeries (CABG) are performed annually at Jackson Memorial Hospital (JMH), the main teaching hospital of the U of M School of Medicine. The study coordinator works in close collaboration with Dr. Ricci, Co-Investigator. Dr. Ricci, working with other cardiac surgeons in his division, will screen all patients scheduled for CABG, and those who satisfy the eligibility criteria listed below will be invited to participate. Over a period of 37 months (between study months 4 and 41) 500 patients will be recruited and initially randomized to 2 groups: one (n=250) to receive conventional PRBC (unwashed PRBC) and the other (n=250) PRBC depleted of MP (washed PRBC). Approximately 50% of CABG will require PRBC transfusion during surgery and approximately 25% after surgery.
The patient population can be further classified into the following subgroups: subgroup 1 (n=100), surgery transfusion with PRBC; subgroup 2 (n =100), surgery transfusion with washed PRBC; subgroup 3 (n =200), without any transfusion; subgroup 1a (n =25), surgery and post-surgery transfusion with PRBC ; subgroup 1b (n =25), no transfusion during surgery but post-surgery transfusion with PRBC; subgroup 2a (n =25), surgery and post surgery transfusion with washed PRBC; group 2b (n =25), no transfusion during surgery but post-surgery transfusion with washed PRBC.
The comparison of major interest for this study is that of Subgroup 1 vs. 2, with approximately 100 patients each. -- Those not requiring transfusion (Subgroups 3, n ≈ 200) will serve as a "pure comparison" group. The remaining patients are those who require post surgery transfusion(s). The characteristics of patients in groups 1a, 1b, 2a, and 2b and their outcomes will be ascertained and they will be included in ancillary analyses. It is anticipated that only a small proportion of patients will require more than one post-surgery transfusion. Data pertaining to 2nd, 3rd, etc post-surgical transfusions will be collected and used for descriptive purposes and ancillary statistical analyses.
1.2. Protocol on Transfusion Algorithm for the Washed PRBC Group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
In Hospital Mortality
时间窗: Within 30 days after CABG surgery
The number of participants who expired during hospital stay after CABG surgery
Difference in Levels of Circulating CD62E+ Endothelial Microparticles 1 Hour Post-surgery
时间窗: Interval between pre-surgery and 1 hour post-surgery
Difference in levels of circulating CD62E+ endothelial microparticles between 1 hour post-surgery and at pre-surgery, i.e. level at 1 hour post-surgery - level at pre-surgery
Occurrence of at Least One Serious Adverse Event (SAE)
时间窗: within 30 days after CABG surgery
Comparison of the two groups with respect to occurrence or not of at least one SAE including sepsis, respiratory failure, multi-organ failure, anaphylactic shock, transfusion-related acute lung injury, MI, stroke, cardiac arrest.
Difference in Levels of Circulating CD41+ Platelet-derived Microparticles 1 Hour Post-surgery
时间窗: interval between presurgery and 1 hour post-surgery
Difference in levels of circulating CD41+ platelet microparticles between at pre-surgery and at 1hour post-surgery, i.e. level at 1hour post-surgery - level at pre-surgery
Difference in Levels of Circulating Annexin V+ Microparticles 1 Hour Post- Surgery
时间窗: Interval between pre-surgery and 1 hour post-surgery
Difference in levels of circulating Annexin V+ microparticles between at pre-surgery and 1 hour post-surgery, i.e. level of Annexin V+ microparticles at 1 hour post-surgery - level of Annexin V+ microparticles at pre-surgery
Difference in Levels of Circulating CD235a+ Red Cell Microparticles 1 Hour Post-surgery
时间窗: Interval between pre-surgery and 1 hour post-surgery
Difference in levels of circulating CD235a+ red cell microparticles between at 1 hour post-surgery and at pre-surgery, i.e. levels at 1 hour post-surgery - level at pre-surgery
One-year Mortality
时间窗: Within one year after CABG surgery
Number participants who expired within one year after CABG surgery
次要结局
- Each Participant's Number of Non-serious Adverse Events(Within 30 days after CABG surgery)
研究者
Wenche Jy
Research Associate Professor
University of Miami