COVID-19 Longitudinal Biomarkers in Lung Injury

Covid19 Clinical Trial

— COLOBILI  

Official title:

COVID-19 Longitudinal Biomarkers in Lung Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04747782
• Other study ID #: COLOBILI v4.2
• Status: Recruiting
• Start date: March 23, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2021
• Source: Unity Health Toronto
• Contact: Marlene Santos
• Phone: 416-360-4000
• Email: Marlene.Santos[@]unityhealth.to
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Covid19
• Critical Illness
• Lung Injury
• Respiration Disorders
• Respiratory Disease
• Respiratory Tract Diseases

Intervention

Other:
• no interventions performed. Just collecting data, blood samples and post-mortem biopsies.
no interventions performed. Just collecting data, blood samples and post-mortem biopsies.

Locations

Country	Name	City	State
Canada	St Michael's Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Andrew Baker

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death in ICU	Death in ICU	within 3 months from admission
Secondary	Days in ICU	Length of hospitalization	within 3 months from admission to the ICU
Secondary	Mechanical ventilation days	Length of mechanical ventilation while in the ICU	within 3 months from admission to the ICU
Secondary	Days of mechanical ventilation rescue measures	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
Secondary	APACHE II score on admission	Acute Physiology And Chronic Health Evaluation II. Min 0, Max 71. Higher scores impart higher mortality risk.	On admission to the ICU
Secondary	SOFA score	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).
Secondary	In hospital death	In hospital death	within 3 months from admission