Trial NCT04346355
Publication Salvarani C, JAMA , 2020 (published paper)
Dates: 2020-03-31 to 2020-06-11
Funding: Mixed (Local resources, the Italian Ministry of Health and Roche)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Italy Follow-up duration (days): 30 | |
| Inclusion criteria | Patients 18 years and older, with an instrumental diagnosis ofCOVID-19 pneumonia confirmed by a positive reverse-transcriptase polymerase chain reaction assay for SARS-CoV-2 in a respiratory tract specimen. Other inclusion criteria were the presence of acute respiratory failure with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FIO2) ratio between 200 and 300 mm/Hg, an inflammatory phenotype defined by a temperature greater than 38 ‘C during the last 2 days, and/or serum C-reactive protein (CRP) levels of 10mg/dL or greater and/or CRP level increased to at least twice the admission measurement. |
| Exclusion criteria | Exclusion criteria included ICU admission, known hypersensitivity to tocilizumab, and any condition preventing future admission to ICU, such as advanced age with multiple comorbidities, as well as the patient’s expressed will to avoid future intubation. |
| Interventions | |
| Treatment
Tocilizumab 8 mg/kg IV, maximum 800 mg, followed by a second dose after 12 hours. |
|
| Control
Standard care Definition of Standard care: Supportive care following the treatment protocols of each center. All drugs were allowed but IL-1 blockers, Jak inhibitors, and tumor necrosis factor inhibitors. Steroids were allowed if already taken before hospitalization. In case of occurrence of documented clinical worsening, patients randomized in both arms could receive any therapy, including steroids, and, for patients randomized in the control arm, tocilizumab. | |
| Participants | |
| Randomized 126 participants (n1=60 / n2= 66) | |
| Characteristics of participants N=126 Mean age : NR 77 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=126 Critical: n=0 | |
| Primary outcome | |
| In the register Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation [ Time Frame: two weeks from participants' allocation to study arm ] Entry into Intensive Care with invasive mechanical ventilation or deat | |
| In the report Clinical worsening within 14 days since randomization, defined by occurrence of 1 of the following events: Admission to ICU with mechanical ventilation; Death ; PaO2/FIO2 ratio >150 mm Hg | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the published article, the trial registries, protocol and supplemental material were used in data extraction and assessment of risk of bias. Data for the outcome Time to clinical improvement were obtained from the Kaplan-Meier curve. The trial was terminated on the decision of the Scientific Committee due to lack of effect and poor enrollment because of the dramatic decrease in the incidence of the disease in Italy at the time. There were some differences between trial registration and published article in inclusion and exclusion criteria. There was no difference in study treatments between trial registration and published article.14 participants in the standard care group crossed over and recieved Tocilizumab after clinical worsening. |