COVID-19 Severe Respiratory Failure
Conditions
Keywords
COVID-19, Respiratory failure, Inhaled DNase, Baricitinib, Tocilizumab, Low molecular weight heparin, Dexamethasone, Anakinra
Brief summary
In patients with COVID-19, severe hypoxemic respiratory failure (SRF) leading to invasive mechanical ventilation (IMV), raises the mortality rate substantially. Thus, the management of patients with SRF to avoid intubation and intensive care admission is a challenging and crucial issue. This study describes, as rescue/compassionate treatment, a therapeutic protocol based on the multi-mechanistic nature of severe COVID-19, using the combination of inhaled DNase, Baricitinib and Tocilizumab on top of standard of care (SOC) consisting of heparin and dexamethasone. COVID-19 patients with SRF who were treated with SOC, SOC plus Anakinra (ANA), and SOC plus Tocilizumab (TOCI) will be studied as comparators. Primary endpoint will be the reduction of the in-hospital mortality rate, whereas secondary endpoints concern intubation rate, days of hospitalization and overall survival as derived from the last follow-up visit, either in-office or remote. This is a non-randomized, open-label, study, conducted in the First Department of Internal Medicine, University Hospital of Alexandroupolis, Greece.
Interventions
DRUGDexamethasone
Dexamethasone 6-8 mg once daily
DRUGLow molecular weight heparin
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
IV administration of Anakinra 200 mg/twice daily for 3-6 days, then 100 mg/twice daily, for up to 10 days in total.
DRUGTocilizumab
IV administration of Tocilizumab as a single dose of 8mg/kg
DRUGBaricitinib
4 mg per os once daily, for up to 14 days (2 mg if GFR: 30 to \<60 ml/min/1.73 m2)
DRUGDornase Alfa Inhalant Product
Inh. 2,500 U/twice daily, for up to 14 days.
Sponsors
Democritus University of Thrace
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. adult patients ≥18 years old, of any gender 2. positive polymerase-chain-reaction (PCR) test for SARS-CoV-2 RNA in nasopharyngeal swab 3. pulmonary infiltrates suggestive of COVID-19 4. severe respiratory failure (SRF) as defined by PaO2/FiO2\<100 mm Hg 5. written informed consent from the patients or legal representatives for the current compassionate therapeutic protocol.
Exclusion criteria
1. need for intubation/IMV during the first 24 hours after the initiation of treatment 2. multi-organ failure, 3. systemic co-infection 4. SRF due to cardiac failure or fluid overload 5. glomerular filtration rate (GFR) \<30 ml/min/1.73 m2) 6. any stage IV solid tumor or immunosuppression due to hematological disorders 7. any immunosuppressive therapy and/or chemotherapy during the last 30 days 8. low patient's functional performance as defined by a Palliative Performance Scale (PPS) score ≤30% 9. pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital mortality rate | Through study completion, an average of 1 year | To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the in-hospital mortality rate in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intubation rate | Through study completion, an average of 1 year | To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the intubation rate in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments. |
| Days of hospitalization | Through study completion, an average of 1 year | To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the days of hospitalization in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments. |
| Overall mortality rate | Follow-up (max: 52 weeks) | To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, affects overall survival in a follow up of a maximum 52 weeks in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments. |
Countries
Greece
Contacts
Primary ContactKonstantinos Ritis, Professor
Backup ContactPanagiotis Skendros, Associate Professor
Outcome results
None listed