Combination of Inhaled DNase, Baricitinib and Tocilizumab in Severe COVID-19

Sponsor
Democritus University of Thrace
Study ID
NCT05279391
Status
Unknown

Conditions

  • COVID-19 Severe Respiratory Failure

Eligibility Criteria

Sex
ALL
Age
18 Years - 100 Years
Healthy Volunteers
Not accepted

Interventions

  • Dexamethasone — DRUG
    Dexamethasone 6-8 mg once daily
  • Low molecular weight heparin — DRUG
    Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
  • Anakinra 100Mg/0.67Ml Inj Syringe — DRUG
    IV administration of Anakinra 200 mg/twice daily for 3-6 days, then 100 mg/twice daily, for up to 10 days in total.
  • Tocilizumab — DRUG
    IV administration of Tocilizumab as a single dose of 8mg/kg
  • Baricitinib — DRUG
    4 mg per os once daily, for up to 14 days (2 mg if GFR: 30 to \<60 ml/min/1.73 m2)
  • Dornase Alfa Inhalant Product — DRUG
    Inh. 2,500 U/twice daily, for up to 14 days.

Study Details

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.

Key Dates

Start date
Oct 25, 2020
Status verified
Mar 2022
Primary completion
Nov 30, 2021
Completion
Dec 31, 2023

Study Design

Enrollment
150 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Active Comparator: 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
  • Active Comparator: TOCI
    Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)
  • Active Comparator: 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)
  • Active Comparator: COMBI
    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 Measure

In-hospital mortality rate [ Time Frame: Through study completion, an average of 1 year ]

Central Contacts