Modulation of Hyperinflammation in COVID-19
关键词
抽象
描述
The coronavirus disease 2019 (COVID-19) is a novel virus that was first reported in December 2019 from Wuhan, China. So far, over 8,000,000 cases have been reported around the globe with >400,000 reported deaths overwhelming hospitals and constraining resources. Death is mainly due to severe acute respiratory syndrome (SARS), requiring mechanical ventilation; however, many hospitals do not have sufficient equipment (i.e. ventilators) to meet the requirements. It had been suggested that severe SARS-related injury may have be related to an excessive reaction of the host's immune system, and a dysregulation of pro-inflammatory cytokines called cytokine storm syndrome. This is characterized by a hyper-inflammatory state leading to fulminant multi-organ failure and elevated cytokine levels. There is a critical and imminent need to identify effective treatments to reduce mortality.
The study team proposes to use slow low-efficiency daily dialysis (SLEDD) to provide an extracorporeal circuit to target this cytokine storm using immunomodulation of neutrophils with a novel leukocyte modulatory device (L-MOD) to generate an anti-inflammatory phenotype, without depletion of circulating factors.
This is a single centre, prospective, randomized controlled pilot study in the Critical Care Trauma Centre at Victoria Hospital and Critical Care at University Hospital London, Ontario. Critical Care at University Hospital is comprised of two units, the Medical-Surgical ICU and the Cardiac Surgical Recovery Unit. The study team will randomize patients with evidence of acute respiratory distress syndrome into one of two groups; either to standard of care for severe COVID-19 infection or to SLEDD with a L-MOD. Slow low-efficiency daily dialysis will be performed twice for approximately 12 hours, 2 days in a row. Blood work will be collected each of these two days before dialysis initiation, at the end of the session, and then after day 4 and no later than day 7 in the ICU. Patients receiving standard of care will have blood work done on day 1, day 2, and after day 4 and no later than day 7of admission. We will also collect a urine sample for all participants before the first dialysis session only and then again after day 4 and no later than day 7 in the ICU.
日期
| 最后验证: | 05/31/2020 |
| 首次提交: | 04/06/2020 |
| 提交的预估入学人数: | 04/15/2020 |
| 首次发布: | 04/19/2020 |
| 上次提交的更新: | 06/14/2020 |
| 最近更新发布: | 06/16/2020 |
| 实际学习开始日期: | 04/27/2020 |
| 预计主要完成日期: | 07/27/2020 |
| 预计完成日期: | 12/31/2020 |
状况或疾病
干预/治疗
Device: Control
Device: SLEDD with a L-MOD
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Sham Comparator: Control Patients diagnosed with severe COVID-19: Those admitted to the intensive care unit with evidence of severe respiratory distress syndrome will undergo standard of care | Device: Control Patients randomized into this group will receive standard of care for COVID-19 infection |
| Active Comparator: SLEDD with a L-MOD Patients diagnosed with severe COVID-19: Those admitted to the intensive care unit with evidence of severe respiratory distress syndrome will undergo slow low efficiency daily dialysis for approximately 12 hours, 2 days in a row with a leukocyte modulatory device. | Device: SLEDD with a L-MOD Patients randomized to this group will undergo slow low efficiency daily dialysis for approximately 12 hours, 2 days in a row with a leukocyte modulatory device. |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Age greater than or equal to 18 years - High clinical suspicion of COVID-19 from the opinion of both infectious disease specialist (s) and the ICU team - Evidence of acute respiratory distress syndrome requiring admission to the Critical Care Trauma Centre Medical Surgical ICU, or the Cardiac Surgical Recovery Unit - Vasopressor support Exclusion Criteria: - Pregnant - Unconfirmed COVID-19 - Chronic immune depression - Contra-indications to regional citrate anticoagulation |
结果
主要结果指标
1. Efficacy of a L-MOD against controls receiving supportive care in ICU. [Through dialysis, on average of 12 hours, two days in a row]
次要成果指标
1. Mortality [From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 months]
2. Hospital Discharge [From date of randomization until the date of hospital discharge or death from any cause, whichever came first, assessed up to 2 months]
3. Leukocyte Monitoring [Through dialysis, on average of 12 hours, two days in a row and again on day 5 in the ICU]
4. Sequential Organ Failure Assessment (SOFA) Score [From date of randomization until the date of ICU discharge or death from any cause, whichever came first, assessed up to 1 months]
5. Intubation length [From date of randomization until the date of ICU discharge up to 2 months]
6. Markers of Inflammation [Through dialysis, on average of 12 hours, two days in a row and again after day 4 and no later than day 7 in the ICU]
7. Leukocytes and Macrophages [Through dialysis, on average of 12 hours, two days in a row and again after day 4 and no later than day 7 in the ICU]
8. Myocardial damage [From date of randomization until the date of ICU discharge up to 2 months]
9. Renal recovery [From date of randomization until the date of ICU discharge up to 2 months]
