Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 6
- 主要终点
- Plasma Viscosity
研究概览
简要总结
Many patients with Coronavirus Disease 2019 (COVID-19) have atypical blood clots. These blood clots can occur in either veins or arteries and be large, like in stroke or heart attack, or very tiny, called microthrombi. Some patients with COVID-19 even have blood clots despite being on anti-clotting medications. Blood with increased viscosity does not flow through the body normally, in the same way that syrup, a highly viscous liquid, and water, a minimally viscous liquid, flow differently. The researchers believe that hyperviscosity may contribute to blood clots and organ damage seen in patients with severe COVID-19. Plasma exchange removes a patient's plasma, which contains the large sticky factors that the researchers believe are increasing viscosity, and replaces it with plasma from healthy donors. In addition to providing important information about plasma exchange as a treatment in COVID-19 for patients, this study will provide data to justify resource and staffing decisions.
This study will enroll 20 participants who are critically ill from COVID-19. Participants will be randomized to receive therapeutic plasma exchange (TPE) or standard of care (SOC).
详细描述
Critically ill COVID-19 patients have high rates of complications, including respiratory failure, renal impairment, and a coagulopathic state that may exacerbate these conditions and contribute to additional end organ injury. Consistent with a fundamentally distinct nature of COVID-19-associated disease, our preliminary studies demonstrate that patients with COVID-19 exhibit an increase in plasma viscosity. Furthermore, the researchers have found that plasma viscosity strongly correlates with sequential organ failure assessment (SOFA) scores, a mortality prediction score used in the intensive care unit (ICU), in COVID-19 infected patients. These results strongly suggest that altered blood flow secondary to hyperviscosity may contribute to end organ injury and therefore morbidity and mortality in the most critically ill COVID-19 patients. More detailed analysis of the potential etiology of COVID-19-associated plasma hyperviscosity has demonstrated that these patients also have significantly elevated levels of the plasma protein fibrinogen. Increased fibrinogen levels, which may be either entirely responsible for or at least contribute to hyperviscosity in these patients, may be the primary mediator of refractory hypercoagulability in this patient population. Thus, hyperviscosity induced by hyperfibrinogenemia may be a critical driver of morbidity and mortality in patients with COVID-19.
Therapeutic plasma exchange (TPE) is the only procedure known to directly and rapidly decrease plasma viscosity, suggesting that TPE may improve patient outcomes in critically ill patients with COVID-19 by decreasing plasma viscosity and thereby enhancing blood flow. However, as a procedure, extensive implementation of TPE would require significant devotion of hospital resources, including apheresis machines and the staff needed to successfully conduct these procedures. The procedures alone require staff to have prolonged interactions with critically ill COVID-19 patients, placing them at a potentially increased risk for contracting COVID-19. It is therefore essential that clear and unequivocal data be generated in order to accurately assess the risk and benefits of this procedure for both patients and staff. Such data will also aid in determining the necessary resources that may be needed to successfully conduct TPE for this patient population.
Participants will be randomized in a 1:1 ratio to receive TPE or SOC. Participants in the TPE study arm will receive two treatments of TPE with frozen plasma on sequential days. Plasma viscosity will be measured before TPE (Day 1) and following the second TPE treatment (Day 3 or 4). Participants in the SOC study arm will also have their plasma viscosity assessed on Days 1 and 3. Participants will be followed for the duration of their hospital stay.
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
- None
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
- •Age ≥ 18 years
- •Patients admitted to the ICU at Emory University Hospital, Emory University Hospital Midtown, or Emory Saint Joseph's Hospital
- •Evidence of COVID-19 infection documented by a laboratory test either by one of the following:
- •A diagnostic test (e.g., nasopharyngeal swab, tracheal aspirate, other)
- •Positive serological test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies
- •Medical records from outside institution
- •Plasma viscosity >2.3 and <3.5 centipoise (cp) or Fibrinogen >800 mg/dL
排除标准
- •Patients with plasma viscosity > 3.5 cp
- •Moribund patients that the ICU clinical team expects to die within 24 hours
- •Patients with any condition that, in the opinion of the clinical team or investigator, could increase the subject's risk by participating in the study or confound the outcome of the study
- •Patients participating in another clinical trial that prohibits the use of TPE
- •Pregnant women
- •Prisoners
结局指标
主要结局
Plasma Viscosity
时间窗: Day 1 (within 24 hours prior to TPE), Day 4 (within 24 hours of last TPE)
Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.
Cumulative Incidence of Adverse Events
时间窗: Up to Day 28
The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.
次要结局
- Cumulative All Cause Mortality(Up to Day 28)
- Cumulative Count of Bleeding and Thromboembolic Complications(Up to Day 28)
- Duration of Hospital Stay(Up to Day 48)
- Clinical Status Score(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- Diastolic Blood Pressure(Days 7, 14, 21, and 28)
- Time to Treatment Failure(Up to Day 28)
- Systolic Blood Pressure(Days 7, 14, 21, and 28)
- Interleukin 6 (IL-6)(Days 7, 14, 21, and 28)
- Prothrombin Time (PT)(Days 7, 14, 21, and 28)
- Duration of ICU Stay(Up to Day 48)
- Discharge Disposition(Up to Day 48)
- Ventilator Days(Up to Day 28)
- Platelet Count(Days 7, 14, 21, and 28)
- Total Protein(Days 7, 14, 21, and 28)
- Body Temperature(Days 7, 14, 21, and 28)
- Heart Rate(Days 7, 14, 21, and 28)
- Respiratory Rate(Days 7, 14, 21, and 28)
- Need for Treatment From a Registered Respiratory Therapist (RRT)(Days 7, 14, 21, and 28)
- Ventilatory Ratio(Days 7, 14, 21, and 28)
- White Blood Count (WBC)(Days 7, 14, 21, and 28)
- Blood Urea Nitrogen (BUN)(Days 7, 14, 21, and 28)
- Creatinine(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- Vasopressor Requirements(Days 7, 14, 21, and 28)
- Sequential Organ Failure Assessment (SOFA) Score(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- International Normalized Ratio (INR)(Days 7, 14, 21, and 28)
- D-dimer(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- Ventilator Oxygen Percent (FiO2)(Days 7, 14, 21, and 28)
- Positive End-Expiratory Pressure (PEEP)(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- Hemoglobin (Hb)(Days 7, 14, 21, and 28)
- Anti-factor Xa (Anti-Xa)(Days 7, 14, 21, and 28)
- Hematocrit (Hct)(Days 7, 14, 21, and 28)
- Mean Platelet Volume (MVP)(Days 7, 14, 21, and 28)
- Bilirubin(Days 7, 14, 21, and 28)
- Albumin(Days 7, 14, 21, and 28)
- C-reactive Protein (CRP)(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
- Activated Partial Thromboplastin Time (aPTT)(Days 7, 14, 21, and 28)
- Fibrinogen(Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28)
研究者
Cheryl Maier
Assistant Professor
Emory University