COVID-19 Severe Respiratory FailureNCT05279391
Combination of Inhaled DNase, Baricitinib and Tocilizumab in Severe COVID-19
A study testing Dexamethasone, Low molecular weight heparin and Anakinra 100Mg/0.67Ml Inj Syringe in people with COVID-19 Severe Respiratory Failure, run by Democritus University of Thrace at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- COVID-19 Severe Respiratory Failure
- What is being tested?
- Dexamethasone, Low molecular weight heparin and Anakinra 100Mg/0.67Ml Inj Syringe
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteGreece
- Study dates
- 25 Oct 2020to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
University Hospital of Alexandroupolis
Alexandroupoli, Evros, 68100
Konstantinos Ritis, Professor, +302551351103, kritis@med.duth.gr
Panagiotis Skendros, Associate Professor, +302551351091, pskendro@med.duth.gr
About this study
Official title: 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.
- Conditions
- COVID-19 Severe Respiratory Failure
- Being tested
- Dexamethasone, Low molecular weight heparin, Anakinra 100Mg/0.67Ml Inj Syringe, Tocilizumab, Baricitinib
- Keywords
- COVID-19, Respiratory failure, Inhaled DNase, Baricitinib, Tocilizumab, Low molecular weight heparin, Dexamethasone, Anakinra
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Dexamethasone 6-8 mg once daily
Low molecular weight heparinDrug
Therapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg)
Anakinra 100Mg/0.67Ml Inj SyringeDrug
IV administration of Anakinra 200 mg/twice daily for 3-6 days, then 100 mg/twice daily, for up to 10 days in total.
TocilizumabDrug
IV administration of Tocilizumab as a single dose of 8mg/kg
BaricitinibDrug
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 ProductDrug
Inh. 2,500 U/twice daily, for up to 14 days.
| Study group | Role | What they receive |
|---|---|---|
| SOC | Active comparator | 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 Receives: Drug: Dexamethasone; Drug: Low molecular weight heparin |
| TOCI | Active comparator | Patients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg) Receives: Drug: Dexamethasone; Drug: Low molecular weight heparin; Drug: Tocilizumab |
| ANA | Active comparator | 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) Receives: Drug: Dexamethasone; Drug: Low molecular weight heparin; Drug: Anakinra 100Mg/0.67Ml Inj Syringe |
| COMBI | Active comparator | Patients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment. Receives: Drug: Dexamethasone; Drug: Low molecular weight heparin; Drug: Tocilizumab; Drug: Baricitinib; Drug: Dornase Alfa Inhalant Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 1 year
Secondary outcomes (3)
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.
Measured: Through study completion, an average of 1 year
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.
Measured: Through study completion, an average of 1 year
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.
Measured: Follow-up (max: 52 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start25 Oct 2020
- Primary completion30 Nov 2021
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19 Severe Respiratory FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Democritus University of Thrace
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Konstantinos Ritis, Democritus University of Thrace
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05279391
- Sponsor's protocol ID
- 87/08-04-2020
- Other IDs
- 16210/20-04-2021
- Status last verified
- Mar 2022
- First submitted
- 11 Mar 2022
- Last updated
- 15 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Administration of Inhaled DNase, Baricitinib and Tocilizumab as Rescue Treatment in Severe COVID-19 Patients
- ClinicalTrials.gov ID
- NCT05279391
- Acronym / sponsor ID
- 87/08-04-2020
- Conditions
- COVID-19 Severe Respiratory Failure
- Keywords
- COVID-19, Respiratory failure, Inhaled DNase, Baricitinib, Tocilizumab, Low molecular weight heparin, Dexamethasone, Anakinra
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Democritus University of ThraceUniversity, hospital or other
- Study start
- 25 Oct 2020 (actual)
- Primary completion
- 30 Nov 2021 (actual)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SOC | Active comparator | Drug: Dexamethasone, Drug: Low molecular weight heparinPatients included in this arm treated with the standard of care (SOC), including dexamethasone plus heparin, with or without the addition of antibiotics and remdesivir |
| TOCI | Active comparator | Drug: Dexamethasone, Drug: Low molecular weight heparin, Drug: TocilizumabPatients included in this arm treated with the SOC plus Tocilizumab (single IV dose: 8mg/kg) |
| ANA | Active comparator | Drug: Dexamethasone, Drug: Low molecular weight heparin, Drug: Anakinra 100Mg/0.67Ml Inj SyringePatients 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) |
| COMBI | Active comparator | Drug: Dexamethasone, Drug: Low molecular weight heparin, Drug: Tocilizumab, Drug: Baricitinib, Drug: Dornase Alfa Inhalant ProductPatients included in this arm treated with the SOC plus the combination of Tocilizumab, Baricitinib and inhaled DNase (COMBI) as a rescue treatment. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneDexamethasone 6-8 mg once daily | Drug | ANA, COMBI, SOC, TOCI |
| Low molecular weight heparinTherapeutic doses of LMWH (e.g. Tinzaparin 175IU/kg) | Drug | ANA, COMBI, SOC, TOCI |
| Anakinra 100Mg/0.67Ml Inj SyringeIV administration of Anakinra 200 mg/twice daily for 3-6 days, then 100 mg/twice daily, for up to 10 days in total. | Drug | ANA |
| TocilizumabIV administration of Tocilizumab as a single dose of 8mg/kg | Drug | COMBI, TOCI |
| Baricitinib4 mg per os once daily, for up to 14 days (2 mg if GFR: 30 to <60 ml/min/1.73 m2) | Drug | COMBI |
| Dornase Alfa Inhalant ProductInh. 2,500 U/twice daily, for up to 14 days. | Drug | COMBI |
Primary outcome
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.
3 secondary outcomes
Intubation rate
Time frame: Through study completion, an average of 1 year
Days of hospitalization
Time frame: Through study completion, an average of 1 year
Overall mortality rate
Time frame: Follow-up (max: 52 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexamethasone, Low molecular weight heparin and Anakinra 100Mg/0.67Ml Inj Syringe in people with COVID-19 Severe Respiratory Failure, run by Democritus University of Thrace at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Konstantinos Ritis, Professor (+302551351103, kritis@med.duth.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In-hospital mortality rate (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.