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Baricitinib for coRona Virus pnEumonia (COVID-19): a THerapeutic Trial (BREATH)

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ClinicalTrials.gov Identifier: NCT04399798
Recruitment Status : Not yet recruiting
First Posted : May 22, 2020
Last Update Posted : May 22, 2020
Sponsor:
Information provided by (Responsible Party):
Carlomaurizio Montecucco, IRCCS Policlinico S. Matteo

Brief Summary:

The objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia.

This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.


Condition or disease Intervention/treatment Phase
Corona Virus Infection Drug: Baricitinib Phase 2

Detailed Description:
Baricitinib 4 mg/daily will be prescribed for 7 days to eligible patients showing signs of acute inflammatory response activation. The primary outcome of the study will be the response to treatment. A patient is considered responder in the absence of either moderate to severe oxygenation impairment or death, whichever occurs first, within 8 days from enrolment. The main secondary outcomes will include the responder rate and mortality at 15 days, the quantification of patients experiencing moderate to severe oxygenation impairment, rate of patients admitted to the intensive care unit, length of hospitalization, mortality at 28 days, rate of re-admission, and adverse events. The duration of the study will be 28 days. In the proof of concept phase, 13 patients will be enrolled; if the responders will be at least 4 patients without safety issues, Baricitinib will be considered for further studies.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia
Estimated Study Start Date : May 15, 2020
Estimated Primary Completion Date : September 15, 2020
Estimated Study Completion Date : November 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Baricitinib active treatment
Baricitinib 4 mg/day
Drug: Baricitinib
4 mg/day for 7 days
Other Name: Olumiant




Primary Outcome Measures :
  1. Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria) [ Time Frame: 8 days ]
    A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

  2. Response to treatment: survival [ Time Frame: 8 days ]
    Absence of death within 8 days from enrollment


Secondary Outcome Measures :
  1. To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days [ Time Frame: 8 days ]
    Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

  2. To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days [ Time Frame: 15 days ]
    Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

  3. Mortality [ Time Frame: 8 days and 15 days ]
    To quantify mortality within 8 and 15 days

  4. Peripheral capillary oxygen saturation (SpO2) [ Time Frame: 8 days; 15 days ]
    SpO2 will be assessed with the median and 25th-75th percentiles

  5. Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2) [ Time Frame: 8 days; 15 days ]
    PaO2/FiO2 will be assessed with the median and 25th-75th percentiles

  6. To assess the rate of patients admitted to the intensive care unit [ Time Frame: 8 days; 15 days ]
    Number of patients over the number of patients enrolled

  7. To measure the length of hospital stay [ Time Frame: 8 days; 15 days ]
    Median number of days and 25th-75th percentiles

  8. 28-day mortality [ Time Frame: 28 days ]
    To quantify 28-day mortality

  9. To quantify the rate of re-admission within 28 days [ Time Frame: 28 days ]
    Number of patients readmitted over the number patients enrolled

  10. To quantify the cumulative incidence and severity of adverse events [ Time Frame: 28 days ]
    Number, type, and severity of adverse events

  11. Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels; [ Time Frame: 15 days ]
    Serial serum assessments from baseline up to 15 days

  12. TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels [ Time Frame: 15 days ]
    Serial serum assessments from baseline up to 15 days

  13. Viral load analyses [ Time Frame: 15 days ]
    Serial assessments from baseline up to 15 days for viral load persistence



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to obtain informed patient consent noting the limitations of existing knowledge regarding Baricitinib's efficacy and the labeled warning and precautions as the proposed use is outside the approved indication, as well as the presence of known risk of being treated with Baricitinib while the subject of an active infection
  • informed Consent as documented by signature
  • patients with a confirmed SARS-CoV-2 pneumonia
  • adult patients aged 18-74 years old
  • infiltrates at chest radiography
  • c-reactive protein level greater than 10 mg/dl or ferritin level > 900 ug/L
  • Lymphocyte count less than 1500/mmc
  • > 200 PaO2/FiO2 ≤ 300

Exclusion Criteria:

  • patients aged < 18 years old and ≥ 75 years old
  • concomitant bacterial infection
  • lymphopenia less than 500/mmc
  • hemoglobin < 8 g/dl
  • absolute neutrophil count < 1 x 109 cells/L
  • requiring continuous positive airway pressure (C-PAP) or mechanical ventilation
  • sudden clinical deterioration requiring intensive care unit access
  • known hypersensitivity or allergy to the study drug
  • Creatinine clearance < 30 mL/min; if the creatinine clearance is between 30 and 60 mL/min the dose of Baricitinib should be reduced to 2 mg/daily
  • Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or moderate hepatic impairment)
  • Pregnant or breast-feeding
  • Active tuberculosis
  • Evidence of active hepatitis B (HBV) (HbsAg positive) or with detectable hepatitis C virus (HCV)-RNA, human immunodeficiency virus (HIV)
  • Ongoing, acute diagnosis of deep venous thrombosis/pulmonary embolism (DVT/PE)
  • Previous diagnosis of DVT/PE

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04399798


Contacts
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Contact: Sara Monti, MD 0382501878 sara.saramonti@gmail.com
Contact: Valentina Zuccaro, MD 0382501080 V.Zuccaro@smatteo.pv.it

Sponsors and Collaborators
IRCCS Policlinico S. Matteo
Investigators
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Principal Investigator: Carlomaurizio Montecucco, Prof Rheumatology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy
Study Chair: Raffaele Bruno, Prof Infectious Diseases; IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy
Publications:
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Responsible Party: Carlomaurizio Montecucco, Prof, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT04399798    
Other Study ID Numbers: 2020-001185-11
First Posted: May 22, 2020    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections