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

Primary Purpose

COVID-19 Severe Respiratory Failure

Status
Recruiting
Phase
Not Applicable
Locations
Greece
Study Type
Interventional
Intervention
Dexamethasone
Low molecular weight heparin
Anakinra 100Mg/0.67Ml Inj Syringe
Tocilizumab
Baricitinib
Dornase Alfa Inhalant Product
Sponsored by
Democritus University of Thrace
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Severe Respiratory Failure focused on measuring COVID-19, Respiratory failure, Inhaled DNase, Baricitinib, Tocilizumab, Low molecular weight heparin, Dexamethasone, Anakinra

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University Hospital of AlexandroupolisRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

SOC

TOCI

ANA

COMBI

Arm 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

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

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)

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

Outcomes

Primary Outcome Measures

In-hospital mortality rate
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 Outcome Measures

Intubation rate
To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the intubation rate in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments.
Days of hospitalization
To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the days of hospitalization in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments.
Overall mortality rate
To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, affects overall survival in a follow up of a maximum 52 weeks in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments.

Full Information

First Posted
March 11, 2022
Last Updated
March 11, 2022
Sponsor
Democritus University of Thrace
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1. Study Identification

Unique Protocol Identification Number
NCT05279391
Brief Title
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

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 25, 2020 (Actual)
Primary Completion Date
November 30, 2021 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Democritus University of Thrace

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Severe Respiratory Failure
Keywords
COVID-19, Respiratory failure, Inhaled DNase, Baricitinib, Tocilizumab, Low molecular weight heparin, Dexamethasone, Anakinra

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SOC
Arm Type
Active Comparator
Arm 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
Arm Title
TOCI
Arm Type
Active Comparator
Arm Description
Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)
Arm Title
ANA
Arm Type
Active Comparator
Arm 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)
Arm Title
COMBI
Arm Type
Active Comparator
Arm Description
Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 6-8 mg once daily
Intervention Type
Drug
Intervention Name(s)
Low molecular weight heparin
Intervention Description
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
Intervention Type
Drug
Intervention Name(s)
Anakinra 100Mg/0.67Ml Inj Syringe
Intervention Description
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
Intervention Name(s)
Tocilizumab
Intervention Description
IV administration of Tocilizumab as a single dose of 8mg/kg
Intervention Type
Drug
Intervention Name(s)
Baricitinib
Intervention Description
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
Intervention Name(s)
Dornase Alfa Inhalant Product
Intervention Description
Inh. 2,500 U/twice daily, for up to 14 days.
Primary Outcome Measure Information:
Title
In-hospital mortality rate
Description
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.
Time Frame
Through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
Intubation rate
Description
To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the intubation rate in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments.
Time Frame
Through study completion, an average of 1 year
Title
Days of hospitalization
Description
To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, reduces the days of hospitalization in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments.
Time Frame
Through study completion, an average of 1 year
Title
Overall mortality rate
Description
To investigate whether the combined administration of inhaled DNase, Baricitinib and Tocilizumab, as a rescue treatment, affects overall survival in a follow up of a maximum 52 weeks in COVID-19 patients with severe respiratory failure compared to standard of care and other immunomodulatory treatments.
Time Frame
Follow-up (max: 52 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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% pregnancy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Konstantinos Ritis, Professor
Phone
+302551351103
Email
kritis@med.duth.gr
First Name & Middle Initial & Last Name or Official Title & Degree
Panagiotis Skendros, Associate Professor
Phone
+302551351090
Email
pskendro@med.duth.gr
Facility Information:
Facility Name
University Hospital of Alexandroupolis
City
Alexandroupolis
State/Province
Evros
ZIP/Postal Code
68100
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Konstantinos Ritis, Professor
Phone
+302551351103
Email
kritis@med.duth.gr
First Name & Middle Initial & Last Name & Degree
Panagiotis Skendros, Associate Professor
Phone
+302551351091
Email
pskendro@med.duth.gr
First Name & Middle Initial & Last Name & Degree
Efstratios Gavriilidis, MD, MSc
First Name & Middle Initial & Last Name & Degree
Christina Antoniadou, MD, MSc

12. IPD Sharing Statement

Learn more about this trial

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

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