NCT05279391

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
150

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Oct 2020

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 25, 2020

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2021

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

March 11, 2022

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 15, 2022

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed
Last Updated

March 15, 2022

Status Verified

March 1, 2022

Enrollment Period

1.1 years

First QC Date

March 11, 2022

Last Update Submit

March 11, 2022

Conditions

Keywords

COVID-19Respiratory failureInhaled DNaseBaricitinibTocilizumabLow molecular weight heparinDexamethasoneAnakinra

Outcome Measures

Primary Outcomes (1)

  • 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.

    Through study completion, an average of 1 year

Secondary Outcomes (3)

  • Intubation rate

    Through study completion, an average of 1 year

  • Days of hospitalization

    Through study completion, an average of 1 year

  • Overall mortality rate

    Follow-up (max: 52 weeks)

Study Arms (4)

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

Drug: DexamethasoneDrug: Low molecular weight heparin

TOCI

ACTIVE COMPARATOR

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

Drug: DexamethasoneDrug: Low molecular weight heparinDrug: 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)

Drug: DexamethasoneDrug: Low molecular weight heparinDrug: 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.

Drug: DexamethasoneDrug: Low molecular weight heparinDrug: TocilizumabDrug: BaricitinibDrug: Dornase Alfa Inhalant Product

Interventions

Dexamethasone 6-8 mg once daily

ANACOMBISOCTOCI

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

ANACOMBISOCTOCI

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

ANA

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

COMBITOCI

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

COMBI

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

COMBI

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Alexandroupolis

Alexandroupoli, Evros, 68100, Greece

RECRUITING

MeSH Terms

Conditions

COVID-19Respiratory Insufficiency

Interventions

DexamethasoneHeparin, Low-Molecular-WeightInterleukin 1 Receptor Antagonist Proteintocilizumabbaricitinib

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesRespiration Disorders

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedHeparinGlycosaminoglycansPolysaccharidesCarbohydratesCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Central Study Contacts

Konstantinos Ritis, Professor

CONTACT

Panagiotis Skendros, Associate Professor

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Internal Medicine, First Department of Internal Medicine

Study Record Dates

First Submitted

March 11, 2022

First Posted

March 15, 2022

Study Start

October 25, 2020

Primary Completion

November 30, 2021

Study Completion

December 31, 2023

Last Updated

March 15, 2022

Record last verified: 2022-03

Locations