Combination of Inhaled DNase, Baricitinib and Tocilizumab in Severe COVID-19
- Conditions
- COVID-19 Severe Respiratory Failure
- Interventions
- Drug: Low molecular weight heparinDrug: Dornase Alfa Inhalant Product
- Registration Number
- NCT05279391
- Lead Sponsor
- Democritus University of Thrace
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 150
- adult patients ≥18 years old, of any gender
- positive polymerase-chain-reaction (PCR) test for SARS-CoV-2 RNA in nasopharyngeal swab
- pulmonary infiltrates suggestive of COVID-19
- severe respiratory failure (SRF) as defined by PaO2/FiO2<100 mm Hg
- written informed consent from the patients or legal representatives for the current compassionate therapeutic protocol.
- need for intubation/IMV during the first 24 hours after the initiation of treatment
- multi-organ failure,
- systemic co-infection
- SRF due to cardiac failure or fluid overload
- glomerular filtration rate (GFR) <30 ml/min/1.73 m2)
- any stage IV solid tumor or immunosuppression due to hematological disorders
- any immunosuppressive therapy and/or chemotherapy during the last 30 days
- low patient's functional performance as defined by a Palliative Performance Scale (PPS) score ≤30%
- pregnancy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description COMBI Low molecular weight heparin Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment. SOC Low molecular weight heparin Patients included in this arm treated with the standard of care (SOC), including dexamethasone plus heparin, with or without the addition of antibiotics and remdesivir TOCI Low molecular weight heparin Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg) TOCI Tocilizumab Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg) ANA Low molecular weight heparin Patients included in this arm treated with the SOC plus Anakinra (200mg twice daily IV for 3-6 days, then 100 mg/twice daily, for up to 10 days in total) COMBI Tocilizumab Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment. ANA Anakinra 100Mg/0.67Ml Inj Syringe Patients included in this arm treated with the SOC plus Anakinra (200mg twice daily IV for 3-6 days, then 100 mg/twice daily, for up to 10 days in total) COMBI Dornase Alfa Inhalant Product Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment. TOCI Dexamethasone Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg) ANA Dexamethasone Patients included in this arm treated with the SOC plus Anakinra (200mg twice daily IV for 3-6 days, then 100 mg/twice daily, for up to 10 days in total) SOC Dexamethasone Patients included in this arm treated with the standard of care (SOC), including dexamethasone plus heparin, with or without the addition of antibiotics and remdesivir COMBI Baricitinib Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment. COMBI Dexamethasone Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
Trial Locations
- Locations (1)
University Hospital of Alexandroupolis
🇬🇷Alexandroupolis, Evros, Greece