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

NCT ID: NCT05279391

Last Updated: 2022-03-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-25
• Study Completion Date: 2023-12-31

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.

Conditions

COVID-19 Severe Respiratory Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Dexamethasone 6-8 mg once daily

Low molecular weight heparin

Intervention Type: DRUG

Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)

TOCI

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Dexamethasone 6-8 mg once daily

Low molecular weight heparin

Intervention Type: DRUG

Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)

Tocilizumab

Intervention Type: DRUG

IV administration of Tocilizumab as a single dose of 8mg/kg

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)

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Dexamethasone 6-8 mg once daily

Low molecular weight heparin

Intervention Type: DRUG

Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)

Anakinra 100Mg/0.67Ml Inj Syringe

Intervention Type: 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.

COMBI

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Dexamethasone 6-8 mg once daily

Low molecular weight heparin

Intervention Type: DRUG

Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)

Tocilizumab

Intervention Type: DRUG

IV administration of Tocilizumab as a single dose of 8mg/kg

Baricitinib

Intervention Type: 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

Intervention Type: DRUG

Inh. 2,500 U/twice daily, for up to 14 days.

Interventions

Dexamethasone

Dexamethasone 6-8 mg once daily

Intervention Type: DRUG

Low molecular weight heparin

Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)

Intervention Type: DRUG

Anakinra 100Mg/0.67Ml Inj Syringe

IV administration of Anakinra 200 mg/twice daily for 3-6 days, then 100 mg/twice daily, for up to 10 days in total.

Intervention Type: DRUG

Tocilizumab

IV administration of Tocilizumab as a single dose of 8mg/kg

Intervention Type: DRUG

Baricitinib

4 mg per os once daily, for up to 14 days (2 mg if GFR: 30 to \<60 ml/min/1.73 m2)

Intervention Type: DRUG

Dornase Alfa Inhalant Product

Inh. 2,500 U/twice daily, for up to 14 days.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Democritus University of Thrace

OTHER

Sponsor Role: lead

Responsible Party

Konstantinos Ritis

Professor of Internal Medicine, First Department of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital of Alexandroupolis

Alexandroupoli, Evros, Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Konstantinos Ritis, Professor

Role: CONTACT

kritis@med.duth.gr

+302551351103

Panagiotis Skendros, Associate Professor

Role: CONTACT

pskendro@med.duth.gr

+302551351090

Facility Contacts

Konstantinos Ritis, Professor

Role: primary

kritis@med.duth.gr

+302551351103

Panagiotis Skendros, Associate Professor

Role: backup

pskendro@med.duth.gr

+302551351091

Other Identifiers

16210/20-04-2021

Identifier Type: OTHER

Identifier Source: secondary_id

87/08-04-2020

Identifier Type: -

Identifier Source: org_study_id