Clinical trial NCT05279391: Combination of Inhaled DNase, Baricitinib and Tocilizumab in Severe COVID-19
Official title: Combined Administration of Inhaled DNase, Baricitinib and Tocilizumab as Rescue Treatment in Severe COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: COVID-19 Severe Respiratory Failure
Keywords: COVID-19
Respiratory failure
Inhaled DNase
Baricitinib
Tocilizumab
Low molecular weight heparin
Dexamethasone
Anakinra
Lead sponsor: Democritus University of Thrace
Sponsor class: OTHER
First posted: 2022-03-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: In-hospital mortality rate
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Intubation rate
timeFrame: Through study completion, an average of 1 year
measure: Days of hospitalization
timeFrame: Through study completion, an average of 1 year
measure: Overall mortality rate
timeFrame: Follow-up (max: 52 weeks)
Other outcomes:
Locations:
city: Alexandroupolis
country: Greece
facility: University Hospital of Alexandroupolis
state: Evros
Study officials:
References: