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

Democritus University of Thrace

Status: Unknown

Conditions: COVID-19 Severe Respiratory Failure

Treatments: Drug: Tocilizumab; Drug: Dexamethasone; Drug: Anakinra 100Mg/0.67Ml Inj Syringe; Drug: Low molecular weight heparin; Drug: Dornase Alfa Inhalant Product; Drug: Baricitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT05279391

87/08-04-2020

16210/20-04-2021 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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150 participants in 4 patient groups

SOC

Active Comparator group

Description:

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

Treatment:

Drug: Low molecular weight heparin

Drug: Dexamethasone

TOCI

Active Comparator group

Description:

Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)

Treatment:

Drug: Tocilizumab

Drug: Low molecular weight heparin

Drug: Dexamethasone

ANA

Active Comparator group

Description:

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)

Treatment:

Drug: Anakinra 100Mg/0.67Ml Inj Syringe

Drug: Low molecular weight heparin

Drug: Dexamethasone

COMBI

Active Comparator group

Description:

Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.

Treatment:

Drug: Tocilizumab

Drug: Low molecular weight heparin

Drug: Baricitinib

Drug: Dexamethasone

Drug: Dornase Alfa Inhalant Product