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

March 11, 2022 updated by: Konstantinos Ritis, Democritus University of Thrace

Combined Administration of Inhaled DNase, Baricitinib and Tocilizumab as Rescue Treatment in Severe COVID-19 Patients

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Konstantinos Ritis, Professor
  • Phone Number: +302551351103
  • Email: kritis@med.duth.gr

Study Contact Backup

  • Name: Panagiotis Skendros, Associate Professor
  • Phone Number: +302551351090
  • Email: pskendro@med.duth.gr

Study Locations

  • Greece
    • Evros
      • Alexandroupolis, Evros, Greece, 68100
        • Recruiting
        • University Hospital of Alexandroupolis
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Efstratios Gavriilidis, MD, MSc
        • Sub-Investigator:
          • Christina Antoniadou, MD, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: Dexamethasone
Dexamethasone 6-8 mg once daily
Drug: Low molecular weight heparin
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
Active Comparator: TOCI
Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg)
Drug: Dexamethasone
Dexamethasone 6-8 mg once daily
Drug: Low molecular weight heparin
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
Drug: Tocilizumab
IV administration of Tocilizumab as a single dose of 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)
Drug: Dexamethasone
Dexamethasone 6-8 mg once daily
Drug: Low molecular weight heparin
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
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.
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.
Drug: Dexamethasone
Dexamethasone 6-8 mg once daily
Drug: Low molecular weight heparin
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
Drug: Tocilizumab
IV administration of Tocilizumab as a single dose of 8mg/kg
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)
Drug: Dornase Alfa Inhalant Product
Inh. 2,500 U/twice daily, for up to 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In-hospital mortality rate
Time Frame: Through study completion, an average of 1 year
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.
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intubation rate
Time Frame: Through study completion, an average of 1 year
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.
Through study completion, an average of 1 year
Days of hospitalization
Time Frame: Through study completion, an average of 1 year
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.
Through study completion, an average of 1 year
Overall mortality rate
Time Frame: Follow-up (max: 52 weeks)
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.
Follow-up (max: 52 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Democritus University of Thrace

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2020

Primary Completion (Actual)

November 30, 2021

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

March 11, 2022

First Submitted That Met QC Criteria

March 11, 2022

First Posted (Actual)

March 15, 2022

Study Record Updates

Last Update Posted (Actual)

March 15, 2022

Last Update Submitted That Met QC Criteria

March 11, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 87/08-04-2020
  • 16210/20-04-2021 (Other Identifier: University Hospital of Alexandroupolis, Greece)

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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