COVIDOSE: Tocilizumab to Prevent Clinical Decompensation in Hospitalized, Non-critically Ill Patients With COVID-19 Pneumonitis

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT04331795
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 2
• Patients Per Site Per Month: 15.7

Study Details

Study Description

Brief Summary

Coronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose.

Hypotheses:

1. Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death.

2. Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death.

Objectives:

1. To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.

2. To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Tocilizumab; Drug: Tocilizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Institution of Tocilizumab Titration in Non-Critical Hospitalized COVID-19 Pneumonitis
• Actual Study Start Date: Apr 4, 2020
• Actual Primary Completion Date: Jun 5, 2020
• Actual Study Completion Date: Jun 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation	Drug: Tocilizumab; Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Experimental: Group B Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation	Drug: Tocilizumab; Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Response in Maximum Temperature (Tmax) [Assessed for the 24 hour period after tocilizumab administration]

   Number of Participants with Clinical Response in Maximum Temperature (Tmax)

2. Number of Participants With Biochemical Response as Determined by CRP Response [Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administration]

   Number of Participants with Biochemical Response as determined by CRP Response. Defined as at least 25% decrease in CRP from baseline at least 16 hours after administration of drug.

Secondary Outcome Measures

1. Overall Survival [28 days]

   28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.

2. Survival to Hospital Discharge [Hospitalization, up to 4 weeks after tocilizumab administration]

   This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.

3. Progression of COVID-19 Pneumonitis [Hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).

4. Rate of Non-elective Mechanical Ventilation [Hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.

5. Duration of Mechanical Ventilation [Hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).

6. Time to Mechanical Ventilation [Assessed over hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.

7. Rate of Vasopressor/Inotrope Utilization [Hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.

8. Duration of Vasopressor/Inotrope Utilization [Hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).

9. Time to Vasopressor or Inotropic Utilization [Assessed over hospitalization, up to 4 weeks after tocilizumab administration]

   This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.

10. Number of ICU Days [Hospitalization, up to 4 weeks after tocilizumab administration]

    Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.

11. Duration of Increased Supplemental Oxygen Requirement From Baseline [Assessed over hospitalization, up to 4 weeks after tocilizumab administration]

    Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults ≥ 18 years of age

• Approval from the patient's primary service

• Admitted as an inpatient to University of Chicago Medicine

• Fever, documented in electronic medical record and defined as: T ≥ 38*C by any conventional clinical method (forehead, tympanic, oral, axillary, rectal)

• Positive test for active SARS-CoV-2 infection

• Radiographic evidence of infiltrates on chest radiograph (CXR) or computed tomography (CT)

• Ability to provide written informed consent on the part of the subject or, in the absence of decisional capacity of the subject, an appropriate surrogate (e.g. a legally authorized representative).

Exclusion Criteria:

• Concurrent use of invasive mechanical ventilation (patients receiving non-invasive mechanical ventilation [CPAP, BiPap, HHFNC] are eligible)

• Concurrent use of vasopressor or inotropic medications

• Previous receipt of tocilizumab or another anti-IL6R or IL-6 inhibitor.

• Known history of hypersensitivity to tocilizumab.

• Patients who are actively being considered for a study of an antiviral agent that would potentially exclude concurrent enrollment on this study.

• Patients actively receiving an investigational antiviral agent in the context of a clinical research study.

• Diagnosis of end-stage liver disease or listed for liver transplant.

• Elevation of AST or ALT in excess of 5 times the upper limit of normal.

• Neutropenia (Absolute neutrophil count < 500/uL).

• Thrombocytopenia (Platelets < 50,000/uL).

• On active therapy with a biologic immunosuppressive agent, which include the following biologics and any biosimilar versions thereof:

• Alemtuzumab

• Blinatumomab

• Brentuximab

• Daratumumab

• Elotuzumab

• Ibritumomab

• Obinutuzumab

• Ofatumumab

• Ocrelizumab

• Rituximab

• Inotuzumab

• Gemtuzumab

• Tositumumab

• Moxetumomab

• Polatuzumab

• Abatacept

• Adalimumab

• Belimumab

• Certolizumab

• Eculizumab

• Etanercept

• Golimumab

• Infliximab

• Ixekizumab

• Rituximab

• Sarilumab

• Secukinumab

• Tocilizumab

• Ustekinumab

• On active therapy with a JAK2-targeted agent, which include the following:

• Tofacitinib

• Baricitinib

• Upadacitinib

• Ruxolitinib

• History of bone marrow transplantation or solid organ transplant.

• Known history of Hepatitis B or Hepatitis C.

• Known history of mycobacterium tuberculosis infection at risk for reactivation.

• Known history of gastrointestinal perforation or active diverticulitis.

• Multi-organ failure as determined by primary treating team

• Any other documented serious, active infection besides COVID-19.

• Pregnant patients

• Patients who are unable to discontinue scheduled antipyretic medications, either as monotherapy (e.g., acetaminophen or ibuprofen [aspirin is acceptable]) or as part of combination therapy (e.g., hydrocodone/acetaminophen, aspirin/acetaminophen/caffeine [Excedrin®])

• CRP < 40 mg/L (or ug/mL)

Patients will be assigned to Group A if:

● C-reactive protein (CRP) ≥ 75 ug/mL

AND

Any one of the following criteria are met:

• Previous ICU admission

• Previous non-elective intubation

• Admission for heart failure exacerbation within the past 12 months

• History of percutaneous coronary intervention (PCI)

• History of coronary artery bypass graft (CABG) surgery

• Diagnosis of pulmonary hypertension

• Baseline requirement for supplemental O2

• Diagnosis of interstitial lung disease (ILD)

• Admission for chronic obstructive pulmonary disease (COPD) exacerbation within the past 12 months

• Asthma with use of daily inhaled corticosteroid

• History of pneumonectomy or lobectomy

• History of radiation therapy to the lung

• History of HIV

• Cancer of any stage and receiving active treatment (excluding hormonal therapy)

• Any history of diagnosed immunodeficiency

• End-stage renal disease (ESRD) requiring peritoneal or hemodialysis

• History of cerebrovascular accident with residual, patient-reported neurologic deficit

• BMI >30 kg/m2

• Supplemental O2 requirement > 6L in the 24 hours prior to enrollment and tocilizumab administration

All other eligible patients assigned to Group B

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Medicine	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Pankti Reid, MD, MPH, University of Chicago, Department of Medicine, Section of Rheumatology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 20, 2020

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT04331795
• Other Study ID Numbers: IRB20-0515
• First Posted: Apr 2, 2020
• Last Update Posted: Jun 9, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: COVID-19; Pneumonia

Study Results

Participant Flow

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Period Title: Overall Study
STARTED	12	20
COMPLETED	12	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Total of all reporting groups
Overall Participants	12	20	32
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	70	66	69
Sex: Female, Male (Count of Participants)
Female	5 41.7%	11 55%	16 50%
Male	7 58.3%	9 45%	16 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 75%	16 80%	25 78.1%
White	1 8.3%	0 0%	1 3.1%
More than one race	0 0%	3 15%	3 9.4%
Unknown or Not Reported	2 16.7%	1 5%	3 9.4%
Region of Enrollment (participants) [Number]
United States	12 100%	20 100%	32 100%
C-Reactive protein (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	175 (83.1)	138 (76.0)	152 (79.2)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Response in Maximum Temperature (Tmax)
Description	Number of Participants with Clinical Response in Maximum Temperature (Tmax)
Time Frame	Assessed for the 24 hour period after tocilizumab administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	12	20
Count of Participants [Participants]	8 66.7%	16 80%

2. Primary Outcome

Title	Number of Participants With Biochemical Response as Determined by CRP Response
Description	Number of Participants with Biochemical Response as determined by CRP Response. Defined as at least 25% decrease in CRP from baseline at least 16 hours after administration of drug.
Time Frame	Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

One patient in Group A and 2 patients in Group B were deceased before measure of CRP.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	11	18
Count of Participants [Participants]	10 83.3%	15 75%

3. Secondary Outcome

Title	Overall Survival
Description	28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	12	20
Count of Participants [Participants]	10 83.3%	17 85%

4. Secondary Outcome

Title	Survival to Hospital Discharge
Description	This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	12	20
Count of Participants [Participants]	1 8.3%	2 10%

5. Secondary Outcome

Title	Progression of COVID-19 Pneumonitis
Description	This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

No data were collected on this outcome. Given the volumes of patients being cared for and demand for radiology services, it proved impractical during the conduct of the trial to re-examine radiographs of every enrolled patient in the absence of a clinical reason.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	0	0

6. Secondary Outcome

Title	Rate of Non-elective Mechanical Ventilation
Description	This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	12	20
Count of Participants [Participants]	2 16.7%	4 20%

7. Secondary Outcome

Title	Duration of Mechanical Ventilation
Description	This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	12	20
Median (Full Range) [days]	2.5	3.5

8. Secondary Outcome

Title	Time to Mechanical Ventilation
Description	This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Time Frame	Assessed over hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	12	20
Median (Full Range) [days]	2	3.5

9. Secondary Outcome

Title	Rate of Vasopressor/Inotrope Utilization
Description	This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

In reviewing inotropic medication utilization, there was a disconnect between orders being placed and medication administration, precluding high-throughput data extraction from electronic health record.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	0	0

10. Secondary Outcome

Title	Duration of Vasopressor/Inotrope Utilization
Description	This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

In reviewing inotropic medication utilization, there was a disconnect between orders being placed and medication administration, precluding high-throughput data extraction from electronic health record.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	0	0

11. Secondary Outcome

Title	Time to Vasopressor or Inotropic Utilization
Description	This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.
Time Frame	Assessed over hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

In reviewing inotropic medication utilization, there was a disconnect between orders being placed and medication administration, precluding high-throughput data extraction from electronic health record.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	0	0

12. Secondary Outcome

Title	Number of ICU Days
Description	Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.
Time Frame	Hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

Median number of ICU days could not be calculated from our records due to lag in timing of ICU admission order placement, ICU arrival, ICU transfer order, and general ward admission order placement. Therefore, no data was collected for this outcome.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	0	0

13. Secondary Outcome

Title	Duration of Increased Supplemental Oxygen Requirement From Baseline
Description	Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.
Time Frame	Assessed over hospitalization, up to 4 weeks after tocilizumab administration

Outcome Measure Data

Analysis Population Description

0 patients analyzed due to heterogeneity in the recording of supplemental oxygen requirement in the electronic health record, complicating data extraction and analysis. There were no patient data collected for this outcome.

Arm/Group Title	Group A	Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L	Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
Measure Participants	0	0

Adverse Events

Time Frame	28 days
Arm/Group Title	Group A		Group B
Arm/Group Description	Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation Tocilizumab: Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L		Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation Tocilizumab: Group B: Low-dose tocilizumab (beginning dose 80mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND CRP decrease is < 25% at 24 hours following tocilizumab administration and CRP > 40mg/L
All Cause Mortality
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		3/20 (15%)
Serious Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/12 (75%)		17/20 (85%)
Blood and lymphatic system disorders
Anemia	1/12 (8.3%)	1	1/20 (5%)	1
Cardiac disorders
QTC prolangulation	0/12 (0%)	0	1/20 (5%)	1
Type II NSTEMO	1/12 (8.3%)	1	0/20 (0%)	0
Atrial Flutter	0/12 (0%)	0	1/20 (5%)	1
Chest pain	1/12 (8.3%)	1	1/20 (5%)	1
Tachycardia	1/12 (8.3%)	1	2/20 (10%)	2
Ear and labyrinth disorders
Blurred vision	1/12 (8.3%)	1	0/20 (0%)	0
Endocrine disorders
Hypokalemia	0/12 (0%)	0	2/20 (10%)	2
Starvation ketosis	1/12 (8.3%)	1	0/20 (0%)	0
Hyperglycemia	0/12 (0%)	0	3/20 (15%)	3
Hyperkalemia	1/12 (8.3%)	1	1/20 (5%)	1
Hypernatremia	0/12 (0%)	0	1/20 (5%)	1
Hypocalcemia	0/12 (0%)	0	1/20 (5%)	1
Hypoglycemia	0/12 (0%)	0	2/20 (10%)	2
Hypophosphatemia	1/12 (8.3%)	1	1/20 (5%)	1
Transaminitis	1/12 (8.3%)	1	1/20 (5%)	1
Gastrointestinal disorders
Nausea	1/12 (8.3%)	1	1/20 (5%)	1
Constipation	2/12 (16.7%)	2	0/20 (0%)	0
Diarrhea	0/12 (0%)	0	1/20 (5%)	1
Dysphagia	0/12 (0%)	0	2/20 (10%)	2
Emisis	1/12 (8.3%)	1	2/20 (10%)	2
Hematoschezia	1/12 (8.3%)	1	0/20 (0%)	0
Thick secretions	1/12 (8.3%)	1	0/20 (0%)	0
General disorders
Fatigue	1/12 (8.3%)	1	1/20 (5%)	1
Fever	1/12 (8.3%)	1	1/20 (5%)	1
Poor appetite	1/12 (8.3%)	1	1/20 (5%)	1
Infections and infestations
H. Pylori infection	0/12 (0%)	0	1/20 (5%)	1
Acinetobacter PNA	1/12 (8.3%)	1	0/20 (0%)	0
Urinary tract infection	1/12 (8.3%)	1	2/20 (10%)	2
BUN elevation	1/12 (8.3%)	1	0/20 (0%)	0
Bilirubin elevation	0/12 (0%)	0	1/20 (5%)	1
Investigations
ALT elevation	0/12 (0%)	0	1/20 (5%)	1
AST elevation	0/12 (0%)	0	1/20 (5%)	1
Creatinine elevation	0/12 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/12 (0%)	0	1/20 (5%)	1
Right arm contracture	1/12 (8.3%)	1	0/20 (0%)	0
Bone mineral disease	1/12 (8.3%)	1	0/20 (0%)	0
Nervous system disorders
Multifocal subacute stroke	1/12 (8.3%)	1	0/20 (0%)	0
Headache	0/12 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Delirium	0/12 (0%)	0	1/20 (5%)	1
Worsening altered mental status	0/12 (0%)	0	1/20 (5%)	1
Renal and urinary disorders
Acute kidney injury	0/12 (0%)	0	3/20 (15%)	3
Chronic kidney disease	0/12 (0%)	0	1/20 (5%)	1
Hematuria	0/12 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)	0	2/20 (10%)	2
Dyspnea	0/12 (0%)	0	2/20 (10%)	2
healthcare-associated pneumonia	0/12 (0%)	0	1/20 (5%)	1
Aspiration event pneumonitis	1/12 (8.3%)	1	0/20 (0%)	0
Pneumothorax	0/12 (0%)	0	1/20 (5%)	1
Pulmonary embolism	0/12 (0%)	0	1/20 (5%)	1
Vascular disorders
Right soleal deep vein thrombosis	0/12 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.