Clinical trial NCT04358614: Baricitinib Therapy in COVID-19
Official title: Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID
Pneumonia
Keywords: COVID-19
BARICITINIB
MODERATE DISEASE
Lead sponsor: Hospital of Prato
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Baricitinib treated patients compared with controls (previously COVID-19 receving standard therapy)
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To assess the safety of baricitinib combined with antiviral (lopinavir-ritonavir) in terms of serious or non-serious adverse events incidence rate.
timeFrame: 2 weeks
Secondary outcomes:
measure: To evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters.
timeFrame: 2 weeks
measure: ICU admission rate
timeFrame: 2 weeks
measure: Discharge rate.
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Prato
country: Italy
facility: Fabrizio Cantini
state: Tuscany
Study officials:
References:
citation: 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. doi: 10.1083/jcb.200108123. Epub 2002 Mar 4.
citation: Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020 Apr 8;369:m1432. doi: 10.1136/bmj.m1432. No abstract available.
citation: Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Rawling M, Savory E, 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. No abstract available.
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. No abstract available.
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. doi: 10.1093/qjmed/94.10.521.