Phase 2 N=32 Treatment

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

COVID-19

Bottom Line

View on ClinicalTrials.gov: NCT04331795 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jun 2022

Primary outcome: Primary: Number of Participants With Clinical Response in Maximum Temperature (Tmax) — 8; 16 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Tocilizumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Chicago
Primary completion: Jun 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Clinical Response in Maximum Temperature (Tmax)	8; 16	—
PRIMARY Number of Participants With Biochemical Response as Determined by CRP Response	10; 15	—
SECONDARY Overall Survival	10; 17	—
SECONDARY Survival to Hospital Discharge	1; 2	—
SECONDARY Progression of COVID-19 Pneumonitis	—	—
SECONDARY Rate of Non-elective Mechanical Ventilation	2; 4	—
SECONDARY Duration of Mechanical Ventilation	2.5; 3.5	—
SECONDARY Time to Mechanical Ventilation	2; 3.5	—
SECONDARY Rate of Vasopressor/Inotrope Utilization	—	—
SECONDARY Duration of Vasopressor/Inotrope Utilization	—	—
SECONDARY Time to Vasopressor or Inotropic Utilization	—	—
SECONDARY Number of ICU Days	—	—
SECONDARY Duration of Increased Supplemental Oxygen Requirement From Baseline	—	—

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.

Eligibility Criteria

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 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04331795). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.