Low-dose Tocilizumab Versus Standard of Care in Hospitalized Patients With COVID-19 (COVIDOSE-2)

March 10, 2026 updated by: University of Chicago

COVIDOSE-2: A Multi-center, Randomized, Controlled Phase 2 Trial Comparing Early Administration of Low-dose Tocilizumab to Standard of Care in Hospitalized Patients With COVID-19 Pneumonitis Not Requiring Invasive Ventilation

Tocilizumab is an effective treatment for severe coronavirus disease 2019 (Covid-19) pneumonia and related inflammation. Given limited global supplies, clarification of the optimal tocilizumab dose is critical. We conducted an open-label, randomized, controlled trial evaluating two different dose levels of tocilizumab in Covid-19 (40mg and 120mg). Randomization was stratified on remdesivir and corticosteroid at enrollment. The primary outcome was the time to recovery. The key secondary outcome was 28-day mortality.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

COVID-19's high mortality may be driven by hyperinflammation. Interleukin-6 (IL-6) axis therapies may reduce COVID-19 mortality. Retrospective analyses of tocilizumab in severe to critical COVID-19 patients have demonstrated survival advantage and lower likelihood of requiring invasive ventilation following tocilizumab administration. The majority of patients have 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.

The investigators hypothesized that a dose of tocilizumab significantly lower than the EMA- and FDA-labeled dose (8mg/kg) as well as the emerging standard of care dose (400mg) may be effective in patients with COVID-19 pneumonitis and hyperinflammation. Advantages to the lower dose of tocilizumab may include lower likelihood of secondary bacterial infections as well as extension of this drug's limited supply. The investigators conducted an adaptive single-arm phase 2 trial (NCT04331795) evaluating clinical and biochemical response to low-dose tocilizumab in patients with COVID-19 pneumonitis and hyperinflammation.

This multi-center, prospective, randomized controlled phase 2 trial -- designed as two sub-studies to allow for the possible emergence of data demonstrating the clinical efficacy of tocilizumab 8mg/kg or 400mg -- formally tests the clinical efficacy of low-dose tocilizumab in COVID-19 pneumonia.

Sub-Study A Primary Objective A: To establish whether low-dose tocilizumab reduces the time to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation, when compared to a tocilizumab-free standard of care.

Hypothesis A: The investigators hypothesize that low-dose tocilizumab, when compared to a tocilizumab-free standard of care, decreases the time to recovery in hospitalized, non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation by three days or more.

Sub-Study B Primary Objective B: To establish whether low-dose tocilizumab is near-equivalent to high-dose tocilizumab (400mg or 8 mg/kg) in reducing the time to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation.

Hypothesis B: The investigators hypothesize that low-dose tocilizumab is near-equivalent to high-dose tocilizumab in reducing the time to clinical recovery in hospitalized, non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
85

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults ≥ 18 years of age
  • Approval from the patient's primary inpatient service
  • Hospitalized
  • Fever, documented in electronic medical record and defined as: T ≥ 38 degrees 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
  • Concurrent use of vasopressor or inotropic medications
  • Previous receipt of tocilizumab or another anti-IL6R or IL-6 inhibitor in the year prior.
  • Known history of hypersensitivity to tocilizumab.
  • Diagnosis of end-stage liver disease or listed for liver transplant.
  • Elevation of AST or ALT in excess of 10 times the upper limit of normal.
  • Neutropenia (Absolute neutrophil count < 500/uL).
  • Thrombocytopenia (Platelets < 50,000/uL).
  • On active therapy with a Bruton's tyrosine kinase-targeted agent, which include the following:
  • Acalabrutinib
  • Ibrutinib
  • Zanubrutinib
  • On active therapy with a JAK2-targeted agent, which include the following:
  • Tofacitinib
  • Baricitinib
  • Upadacitinib
  • Ruxolitinib
  • Any of the following biologic immunosuppressive agent (and any biosimilar versions thereof) administered in the past 6 months or less::
  • Abatacept
  • Adalimumab
  • Alemtuzumab
  • Atezolizumab
  • Belimumab
  • Blinatumomab
  • Brentuximab
  • Certolizumab
  • Daratumumab
  • Durvalumab
  • Eculizumab
  • Elotuzumab
  • Etanercept
  • Gemtuzumab
  • Golimumab
  • Ibritumomab
  • Infliximab
  • Inotuzumab
  • Ipilimumab
  • Ixekizumab
  • Moxetumomab
  • Nivolumab
  • Obinutuzumab
  • Ocrelizumab
  • Ofatumumab
  • Pembrolizumab
  • Polatuzumab
  • Rituximab
  • Rituximab
  • Sarilumab
  • Secukinumab
  • Tocilizumab
  • Tositumumab
  • Tremelimumab
  • Urelumab
  • Ustekinumab
  • History of bone marrow transplantation (including chimeric antigen receptor T-cell) or solid organ transplant
  • Known history of Hepatitis B or Hepatitis C (patients who have completed curative-intent anti-HCV treatments are not excluded from trial)
  • Positive result on hepatitis B or C screening
  • Known history of mycobacterium tuberculosis infection at risk for reactivation
  • Known history of gastrointestinal perforation
  • Active diverticulitis
  • Multi-organ failure as determined by primary treating physicians
  • Any other documented serious, active infection besides COVID-19 - including but not limited to: lobar pneumonia consistent with bacterial infection, bacteremia, culture-negative endocarditis, or current mycobacterial infection - at the discretion of primary treating physicians
  • Pregnant patients or nursing mothers
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Sub-study A, Tocilizumab-Free Standard of Care
Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive no tocilizumab.
Other: Standard of Care
Tocilizumab-Free Standard of Care
Other: Standard of Care
Tocilizumab 400mg or 8mg/kg
Experimental: Sub-study A, Tocilizumab 40mg
Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive tocilizumab 40mg.
Drug: Tocilizumab
Tocilizumab 40mg
Other Names:
  • Tocilizumab 40mg
Drug: Tocilizumab
Tocilizumab 120mg
Other Names:
  • Tocilizumab 120mg
Experimental: Sub-study A, Tocilizumab 120mg
Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive tocilizumab 120mg.
Drug: Tocilizumab
Tocilizumab 40mg
Other Names:
  • Tocilizumab 40mg
Drug: Tocilizumab
Tocilizumab 120mg
Other Names:
  • Tocilizumab 120mg
Active Comparator: Sub-study B, Tocilizumab 400mg or 8mg/kg Standard of Care
Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab dose (400mg or 8mgkg).
Other: Standard of Care
Tocilizumab-Free Standard of Care
Other: Standard of Care
Tocilizumab 400mg or 8mg/kg
Experimental: Sub-study B, Tocilizumab 40mg
Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab 40mg.
Drug: Tocilizumab
Tocilizumab 40mg
Other Names:
  • Tocilizumab 40mg
Drug: Tocilizumab
Tocilizumab 120mg
Other Names:
  • Tocilizumab 120mg
Experimental: Sub-study B, Tocilizumab 120mg
Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab 120mg.
Drug: Tocilizumab
Tocilizumab 40mg
Other Names:
  • Tocilizumab 40mg
Drug: Tocilizumab
Tocilizumab 120mg
Other Names:
  • Tocilizumab 120mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to Recovery
Time Frame: 28 days
Day of recovery is defined as the first day on which the patient achieves one of the following two categories from the seven-point ordinal scale: 6) Hospitalized, not requiring supplemental oxygen or ongoing medical care or 7) Not hospitalized. Time to recovery is the number of days from randomization to achievement of this status. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Achievement of Recovery
Time Frame: 7 days
This will be defined as the percentage of patients in a given arm of the study achieving one of the above two categories on the ordinal scale on day 7. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.
7 days
Overall Survival
Time Frame: 28 days
This will be defined as the percentage of patients in a given arm of the study who are alive thirty days following randomization. Patients who are discharged to hospice will be counted as deceased on the day of discharge. Patients who are transitioned to inpatient hospice or inpatient comfort measures only will be counted as deceased on the day of transition.
28 days
Hospital Length of Stay
Time Frame: Up to 1 year
This will be defined as the number of days that pass between the day of a patient's randomization and his or her discharge from the hospital.
Up to 1 year
Clinical Response: Maximum Temperature (Tmax) Response
Time Frame: 24 hours
Maximum temperature within 24-hour periods of time immediately prior to, immediately following, and then every 24 hours thereafter randomization. The primary endpoint is a measured Tmax in the 24-hour period immediately following randomization that is lower than the measured Tmax in the 24-hour period immediately preceding randomization.
24 hours
Clinical Response: Rate of Non-Elective Invasive Mechanical Ventilation
Time Frame: Up to 28 days
This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of invasive mechanical ventilation during the course of the patient's COVID-19 infection.
Up to 28 days
Clinical Response: Duration of Non-Elective Invasive Mechanical Ventilation
Time Frame: Up to 28 days
This will be a continuous outcome defined by the amount of time between initiation and cessation of non-elective invasive mechanical ventilation.
Up to 28 days
Clinical Response: Time to Non-Elective Invasive Mechanical Ventilation
Time Frame: Up to 28 days
This will be a continuous outcome defined by the amount of time between randomization and the initiation of non-elective invasive mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Up to 28 days
Clinical Response: Rate of Vasopressor/Inotrope Utilization
Time Frame: Up to 28 days
This will be a binary outcome defined as utilization of any vasopressor or inotropic medication.
Up to 28 days
Clinical Response: Duration of Vasopressor/Inotrope Utilization
Time Frame: Up to 28 days
This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor medications.
Up to 28 days
Clinical Response: Time to Vasopressor/Inotrope Utilization
Time Frame: Up to 28 days
This will be a continuous outcome defined by the amount of time between randomization and the initiation of any vasopressor or inotropic medication. This will be treated as a time-to-event with possible censoring.
Up to 28 days
Biochemical Response: C-reactive Protein Response Rate
Time Frame: 24 hours
This will be a binary outcome defined as the presence or absence of a decline in CRP of ≥ 25% from baseline CRP in the 27 +/- 3 hours after tocilizumab administration, as compared to pre-treatment baseline.
24 hours
Safety: Rate of Secondary Infection
Time Frame: 28 days
This will be defined as the percentage of patients in a study arm who develop serious non-COVID-19 viral, bacterial, or fungal infections (e.g., bloodstream infection, hospital-acquired pneumonia, ventilator-associated pneumonia, opportunistic infection) following randomization and up to the 28-day assessment of overall survival.
28 days
Clinical Response: Duration of Increased Supplemental Oxygen From Baseline
Time Frame: 28 days
This will be an ordinal outcome defined by the number of days counted from randomization over which the participant requires supplemental oxygen in excess over 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.
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Chicago

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Pankti D Reid, MD, MPH, University of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 10, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 10, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB20-1179

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results of this article, after de-identification. Sharing period will be 1 month after data are published and available indefinitely thereafter. Researchers who provide methodologically sound proposals for the purposes of achieving stated aims in their proposal will be eligible for data-sharing.

IPD Sharing Time Frame

From 1 month following publication of data. Available indefinitely thereafter.

IPD Sharing Access Criteria

Proposals will need to be sent to study principal investigators. Requestors will need to sign a data access request form. Link to be determined.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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