Combined Administration of Inhaled DNase, Baricitinib and Tocilizumab as Rescue Treatment in Severe COVID-19 Patients
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- In-hospital mortality rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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%
Arms & Interventions
SOC
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
Intervention: Dexamethasone (Drug)
SOC
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
Intervention: Low molecular weight heparin (Drug)
TOCI
Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)
Intervention: Dexamethasone (Drug)
TOCI
Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)
Intervention: Low molecular weight heparin (Drug)
TOCI
Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)
Intervention: Tocilizumab (Drug)
ANA
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)
Intervention: Dexamethasone (Drug)
ANA
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)
Intervention: Low molecular weight heparin (Drug)
ANA
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)
Intervention: Anakinra 100Mg/0.67Ml Inj Syringe (Drug)
COMBI
Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
Intervention: Dexamethasone (Drug)
COMBI
Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
Intervention: Low molecular weight heparin (Drug)
COMBI
Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
Intervention: Tocilizumab (Drug)
COMBI
Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
Intervention: Baricitinib (Drug)
COMBI
Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
Intervention: Dornase Alfa Inhalant Product (Drug)
Outcomes
Primary Outcomes
In-hospital mortality rate
Time Frame: 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 Outcomes
- Days of hospitalization(Through study completion, an average of 1 year)
- Overall mortality rate(Follow-up (max: 52 weeks))
- Intubation rate(Through study completion, an average of 1 year)
Investigators
Konstantinos Ritis
Professor of Internal Medicine, First Department of Internal Medicine
Democritus University of Thrace