Trial NCT04330638
Publication COV-AID, Unpublished, 2021 ( )
Dates: 2020-04-03 to 2020-06-12
Funding: Public/non profit (The Belgian Health Care Knowledge Centre (KCE, Federaal Kenniscentrum
voor de Gezondheidszorg)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Belgium Follow-up duration (days): 90 | |
| Inclusion criteria | Recent ( ≥ 6 days of flu-like symptoms or malaise yet ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19; Confident COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period; In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion; Presence of hypoxia defined as PaO2/FiO2 below 350 while breathing room air in upright position or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation signs of cytokine release syndrome defined as ANY of the following: serum ferritin concentration >1000 mcg/L and rising since last 24h, single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device or mechanical ventilation, lymphopenia defined as <800 lymphocytes/microliter) and two of the following extra criteria, Ferritin > 700 mcg/L and rising since last 24h, increased LDH (above 300 IU/L) and rising last 24h, D-Dimers > 1000 ng/mL and rising since last 24h, CRP above 70mg/L and rising since last 24h and absence of bacterial infection, if three of the above are present at admission, no need to document 24h rise; Chest X-ray or CT scan showing bilateral infiltrates within last 2 days; Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients; Age ≥ 18yrs; Male or Female; Willing and able to provide informed consent or legal representative willing to provide informed consent |
| Exclusion criteria | Patients with known history of serious allergic reactions, including anaphylaxis, to any of the study medications, or any component of the product; mechanical ventilation > 24 h at Randomization; Patient on ECMO at time of screening; clinical frailty scale above 3 (This frailty score is the patient status before first symptoms of COVID-19 episode.); active bacterial or fungal infection; unlikely to survive beyond 48h; neutrophil count below 1500 cells/microliter; platelets below 50.000/microliter; Patients enrolled in another investigational drug study; patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent) for COVID-19 unrelated disorder; patients on immunosuppressant or immunomodulatory drugs; patients on current anti-IL1 or anti-IL6 treatment ;signs of active tuberculosis; serum transaminase levels >5 times upper limit of normal; bowel perforation or diverticulitis; pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening); Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Woùmen of childbearing potential must consistently and correctly use (during the entire treatment period and 3 months after last reatment) 1 highly effective method for contraception. |
| Interventions | |
| Treatment
Tocilizumab 8 mg/kg (max 800mg) IV once-off |
|
| Control
Standard care ( / ) Definition of Standard care: * | |
| Participants | |
| Randomized 153 participants (n1=81 / n2= 72) | |
| Characteristics of participants N=153 Mean age : NR 116 males Severity : Mild: n=* / Moderate: n=*/ Severe: n=* Critical: n=17 | |
| Primary outcome | |
| In the register Time to Clinical Improvement at day 15 | |
| In the report NR | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated
|
| 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 |
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| General comment |