Baricitinib Therapy in COVID-19

Pneumonia Clinical Trial

Official title:

Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04358614
• Other study ID #: HPrato-4
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 16, 2020
• Est. completion date: April 7, 2020

Study information

• Verified date: April 2020
• Source: Hospital of Prato
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Retrospective study on the efficacy of baricitinib in 12 COVID-19 patients with moderate pneumonia.

Description:

Baricitinib, an anti-Janus kinase inhibitor (anti-JAK) acting against JAK1 and JAK2 that inhibits JAK1- and JAK2-mediated cytokine release, was recently described using BenevolentAI's proprietary artificial intelligence-derived knowledge graph, as an agent that reduces the endocytosis into target cells, and to inhibit the entry. Based on its potential action on inhibition of SARS-CoV-2 entry, and on its known effects on reduction of cytokine release, baricitinib therapy was proposed in patients with moderate pneumonia to explore: the safety of this drug combined with antiviral (lopinavir-ritonavir) in COVID-19; as second outcome, to evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters, and reduction of ICU admission.

Baricitinib was combined with antivirals because it does not interact with them due to its prevalent renal elimination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 7, 2020
• Est. primary completion date: April 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• SARS-Co-V2 positivitity to the nasal-swab by reverse-transcriptase-polymerase chain- reaction (RT-PCR) assay tested by the local diagnostic laboratory

• Age >18 and <85 years

• Presence of at least 3 of the following symptoms as present fever, cough, myalgia, fatigue.

• Presence of radiological findings of pneumonia assessed by chest radiograph, computed tomography, or pulmonary ultrasound.

• Peripheral capillary oxygen saturation (SpO2) > 92% on room air at screening

• PaO2/FiO2 >100-300 mmHg at arterial blood gas analysis.

Exclusion Criteria:

• Age < 18 and >85

• History of thrombophlebitis

• Latent tuberculosis infection (based on the positivity to QuantiFERON Plus positivity, Qiagen, Germany)

• Pregnancy and lactation

• History of malignancies over the previous 5 years, current diagnosis of malignancy

• Inability or unwillingness to sign a written consent.

• Transaminases values 4-fold higher than the upper normal limit.

• HBV and HCV positivity.

• Current Herpes zoster infection.

• Evidence of concomitant bacterial infections.

Related Conditions & MeSH terms

• COVID
• Pneumonia

Intervention

Drug:
• Baricitinib 4 MG Oral Tablet
Baricitinib+antiviral therapy administration for 2 weeks

Locations

Country	Name	City	State
Italy	Fabrizio Cantini	Prato	Tuscany

Sponsors (1)

Lead Sponsor	Collaborator
Fabrizio Cantini

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Conner SD, Schmid SL. Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. J Cell Biol. 2002 Mar 4;156(5):921-9. Epub 2002 Mar 4. — View Citation

Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020 Apr 8;369:m1432. doi: 10.1136/bmj.m1432. — View Citation

Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020 Feb 15;395(10223):e30-e31. doi: 10.1016/S0140-6736(20)30304-4. Epub 2020 Feb 4. — View Citation

Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020 Apr;20(4):400-402. doi: 10.1016/S1473-3099(20)30132-8. Epub 2020 Feb 27. — View Citation

Subbe CP, Kruger M, Rutherford P, Gemmel L. Validation of a modified Early Warning Score in medical admissions. QJM. 2001 Oct;94(10):521-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the safety of baricitinib combined with antiviral (lopinavir-ritonavir) in terms of serious or non-serious adverse events incidence rate.	All adverse event recording	2 weeks
Secondary	To evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters.	The percentage of patients improving the clinical and respiratory parameters compared with controls.	2 weeks
Secondary	ICU admission rate	The percentage of ICU admission in baricitinib group as compared with controls.	2 weeks
Secondary	Discharge rate.	The percentage of discharged in baricitinib group as compared with controls.	2 weeks