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COVID-19 Longitudinal Biomarkers in Lung Injury (COLOBILI)

2021年2月9日 更新者:Dr. Andrew Baker

Profile known and novel biomarkers in blood in COVID19 patients to characterize the host response to SARS-CoV-2 over time and in response to treatment.

The investigators aim to:

  • Better understand the disease. The investigators will achieve this by characterizing the biology of COVID-19 infection and the pathophysiology of the host response using clinical data together with cellular and molecular measurements over the course of the disease. This will allow better insights for the discovery and development of novel therapeutics.
  • Understand why different patients have different phenotypes and disease presentations over time. The investigators will achieve this by analyzing for patient subgroups. This will allow targeted patient stratification and better matching of resources.
  • Understand how patients are responding to the different medications being tested in clinical trials. The investigators will achieve that by co-enrolling with therapeutic trials. This will allow an understanding of the biological effects of these interventions.

Study Design: Observational adaptive study of a translational nature, combining clinical data and basic science investigations in blood samples in the same patients, longitudinally, with serial interim analyses.

Primary outcomes: 90 day ICU mortality. Secondary outcomes: measures of ICU utilization and disease severity, and 90 day in-hospital mortality.

The study ends after 3 months from admission to the ICU, hospital discharge or death.

Location: St. Michael's Hospital (Unity Health Toronto), an academic center in downtown Toronto affiliated with the University of Toronto.

The investigators will collect: A) Detailed clinical data including investigations, mechanical ventilation and cardiovascular parameters. B) Blood samples for state-of-the-art multi-omics biomarker discovery and development: cytokines, anti-COVID19 antibodies, autoimmune serology, metabolomics, transcriptomics, epigenomics, deep immune phenotyping, viral loads. For those patients who die with COVID19 The investigators will perform bedside post-mortem biopsies of lung, heart, kidney and muscle.

Sampling times: From admission to the maximal severity phase through convalescence, in order to capture the evolution and dynamics of the disease and the recovery process: days 0,1, 3, 5, 7, 10, 15 and 22, and then every 2 weeks until the end of the study (3 months from admission to the ICU, hospital discharge or death).

研究概览

研究类型

观察性的

注册 (预期的)

200

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

取样方法

非概率样本

研究人群

Patients admitted to the critical care unit or general medicine ward in a tertiary referral medical center.

描述

  • Primary Cohort: Patients admitted to the ICU with respiratory deterioration suspected or confirmed to be due to SARS-CoV-2. Suspicion will be based on the clinical criteria in place at SMH, with the threshold for inclusion being a suspicion high enough to use PPE until confirmatory testing results are obtained. Only patients found to be COVID19 positive will stay in this cohort. This population will be called "ICU Positive".
  • Secondary Cohort: Patients admitted to the ICU for any reason who are COVID19 positive, regardless of admission date or when they are found to be COVID19 positive. This population will be called "ICU Positive - delayed"
  • Biological controls in the ICU: Any patients from the primary cohort who are found to be COVID19 negative. This population will be called "ICU negative".
  • Biological controls outside the ICU: Patients admitted to the floor with respiratory deterioration suspected or confirmed to be due to SARS-CoV-2, or that develop such respiratory deterioration within 15 days of admission (i.e. become "persons under investigation"). Suspicion will be based on the clinical criteria in place at SMH, with the threshold for inclusion being a suspicion high enough to use PPE until confirmatory testing results are obtained. Only patients found to be COVID19 positive will stay in this cohort. If these patients require ICU admission within 15 days, they will cross-over to the "ICU positive" cohort and count towards that cohort (i.e. number of recruited patients). If they don't require ICU admission within 15 days, they will stay in this cohort and be called "never ICU".
  • Healthy volunteers: The investigators will recruit healthy volunteers among healthcare workers and allied personnel in the hospital. They will provide peripheral blood to serve as: a) independent controls for experimental and laboratory variables, and b) references of healthy baseline state for experiments.
  • A patient previously enrolled as a COVID negative can be re-enrolled in a subsequent hospitalization with a new study ID (i.e. counts as another encounter for the total enrollment). The records will be linked to indicate they represent the same person enrolled again.

Exclusion Criteria

  • Refusal to participate.
  • Inability to record the primary outcome during the first 2 weeks.
  • For the ICU positive and ICU negative cohorts only: failure to obtain the day 0 or 1 blood sample (for example technical problems, or identification of COVID-19 after ICU admission i.e. there was no suspicion on admission).
  • For the ward patients, inability to collect day 1 or 2 blood sample.
  • Known to have had COVID in the past (>4 weeks) in any setting.
  • Healthy volunteers only: COVID19 known or suspected infection, or unprotected exposure to a known acutely ill COVID19 patient in the past 4 weeks; and/or currently unwell or in the course of an acute illness.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 观测模型:队列
  • 时间观点:预期

队列和干预

团体/队列
干预/治疗
COVID positive
Patients admitted to the ICU with respiratory distress found to be COVID19 positive.
no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
COVID negative
Patients admitted to the ICU with respiratory distress found to be COVID19 negative
no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
COVID positive delayed
Patients admitted to the ICU for an indication other than respiratory distress, found to be COVID19 positive.
no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
never-ICU
Patients admitted to the internal medicine ward with respiratory distress found to be COVID19 positive.
no interventions performed. Just collecting data, blood samples and post-mortem biopsies.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Death in ICU
大体时间:within 3 months from admission
Death in ICU
within 3 months from admission

次要结果测量

结果测量
措施说明
大体时间
Days in ICU
大体时间:within 3 months from admission to the ICU
Length of hospitalization
within 3 months from admission to the ICU
Mechanical ventilation days
大体时间:within 3 months from admission to the ICU
Length of mechanical ventilation while in the ICU
within 3 months from admission to the ICU
Days of mechanical ventilation rescue measures
大体时间:within 3 months from admission to the ICU
Number of days on which the patient was treated with one or more of the following rescue meaures: neuromuscular blockade, inhaled NO, proning.
within 3 months from admission to the ICU
APACHE II score on admission
大体时间:On admission to the ICU
Acute Physiology And Chronic Health Evaluation II. Min 0, Max 71. Higher scores impart higher mortality risk.
On admission to the ICU
SOFA score
大体时间:On the same days as blood sampling: days 0,1, 3, 5, 7, 10, 15 and 22, and then every 2 weeks until the end of the study (3 months from admission to the ICU, hospital discharge or death).
Sequential Organ Failure Assessment, calculated daily. Min 6, Max 24. Higher scores impart higher mortality risk.
On the same days as blood sampling: days 0,1, 3, 5, 7, 10, 15 and 22, and then every 2 weeks until the end of the study (3 months from admission to the ICU, hospital discharge or death).
In hospital death
大体时间:within 3 months from admission
In hospital death
within 3 months from admission

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Andrew J Baker, MD、Unity Health Toronto

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2020年3月23日

初级完成 (预期的)

2021年10月1日

研究完成 (预期的)

2021年12月31日

研究注册日期

首次提交

2021年2月3日

首先提交符合 QC 标准的

2021年2月9日

首次发布 (实际的)

2021年2月10日

研究记录更新

最后更新发布 (实际的)

2021年2月10日

上次提交的符合 QC 标准的更新

2021年2月9日

最后验证

2021年2月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

未定

IPD 计划说明

Depends on the type of data requested

药物和器械信息、研究文件

研究美国 FDA 监管的药品

研究美国 FDA 监管的设备产品

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