This is a single arm, prospective, observational, single center study to assess the role of interleukin-6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) as predictors of efficacy and safety outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab. At least 30 patients will be enrolled who are diagnosed with severe COVID-19 pneumonia and meet the entry criteria.
Patients must be at least 18 years of age with severe COVID-19 pneumonia (and/or ARDS)
confirmed per World Health Organization (WHO) criteria, and evidence of pulmonary
infiltration (by chest X-ray and/or CT scan), including a virological confirmation of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive polymerase chain
reaction (PCR) of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid.
At the time of enrollment, patients have to fulfill criteria of the local recommendations for
the treatment with tocilizumab (TCZ): hypoxemia (defined as arterial oxygen partial
pressure/fraction of inspired oxygen (PaO2/FiO2) ratio ≤300 mmHg and/or peripheral capillary
oxygen saturation (SpO2) ≤93%) regardless of the oxygenation method including low-flow oxygen
administration on nasal cannula or mask with oxygen flow rate of > 12 liters per minute,
high-flow oxygen through nasal cannula, noninvasive ventilation (NIV) whatever the modalities
of ventilation, invasive ventilation through tracheal intubation or tracheostomy, and
extracorporeal oxygenation, despite being on standard of care (SOC), which may include
anti-viral treatment, low dose steroids, antimalarials and supportive treatment and care.
Patients in whom, in the opinion of the treating physician, progression to death is imminent
and inevitable within the next 24 hours, will be excluded from the study. Patients with
active tuberculosis (TB) or suspected active bacterial, fungal, viral, or other infection
(besides COVID-19) will be excluded from the study.
Patients will receive one infusion of TCZ 8 mg/kg i.v., with a maximum dose of 800 mg, and
SOC treatment according to local guidelines (hydroxychloroquine or/and lopinavir/ritonavir
or/and remdesivir).
If the clinical signs or symptoms worsen or do not improve (reflected by sustained fever or
at least a one-category worsening on the 7-category ordinal scale of clinical status), one
additional infusion of blinded treatment of TCZ or placebo may be given, after more than 12
hours per local protocol.
The study assessments to be conducted include the following: physical examination, vital
signs, oxygen saturation, assessment of consciousness, presence and absence of respiratory
support, adverse events, concomitant therapies, clinical laboratory tests, and nasopharyngeal
swabs.
Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]
1 - 8 mg per kg of body weight once, maximal 800 mg per dose (can be repeated once more after 12 hours, per clinician's assessment)
Other Name: RoActemra, Anatomical Therapeutic Chemical (ATC) Code L04AC07
Inclusion Criteria:
- Signed Informed Consent Form by any patient capable of giving consent, or, when the
patient is not capable of giving consent, by his or her legal/authorized
representative
- Age ≥18years at time of signing Informed Consent Form
- Ability to comply with the study protocol, in the investigator's judgment
- Hospitalized due to severe COVID-19 pneumonia (and/or ARDS) confirmed per World Health
Organization criteria, and evidence of pulmonary infiltration (by chest X-ray and/or
CT scan), including a virological confirmation of SARS-CoV-2 infection by positive PCR
of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid
- Hypoxemia (defined as a PaO2/FiO2 ratio ≤300 mmHg and/or SpO2≤93%) regardless of their
oxygenation device (including low-flow oxygen administration on nasal cannula or mask
with oxygen flow rate of > 12 liters per minute), high-flow oxygen through nasal
cannula, noninvasive ventilation (NIV) whatever the modalities of ventilation,
invasive ventilation through tracheal intubation or tracheostomy, and extracorporeal
oxygenation, despite being on SOC, which may include anti-viral treatment, low dose
steroids, and supportive care
Exclusion Criteria:
- Known severe allergic reactions to TCZ or other monoclonal antibodies
- Active TB infection
- Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
- In the opinion of the investigator, progression to death is imminent and inevitable
within the next 24 hours, irrespective of the provision of treatments
- Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the
past 6 months
- alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >10 times the upper
limit of the normality detected within 24 hours at screening or at baseline
- absolute neutrophil count (ANC) <1000/µL at screening and baseline
- Platelet count <50,000/µL at screening and baseline
- Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
- Any serious medical condition or abnormality of clinical laboratory tests that, in the
investigator's judgment, precludes the patient's safe participation in the study
University Hospital for Infectious Diseases "Dr Fran Mihaljevic"
Zagreb, Croatia
Investigator: Rok Civljak, MD, PhD
Contact: ++385914012547
rcivljak@bfm.hr
Investigator:
Rok Civljak, MD, PhD
++385914012547
rcivljak@bfm.hr
Arijana Pavelic, BA
++385914012584
apavelic@bfm.hr
Rok Civljak, MD, PhD, Principal Investigator
University Hospital for Infectious Diseases "Dr Fran Mihaljevic"