Baricitinib in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study.

NCT04320277 | Unknown Phase 2

• 1 other identifier: HPrato-3
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. Baricitinib, an anti-Janus kinase inhibitor (anti-JAK) acting against JAK1 and JAK2. The drug was found capable to reduce or interrupt the passage of the virus into target cells, and to inhibit the JAK1- and JAK2-mediated cytokine release. The drug was licensed for the treatment of rheumatoid arthritis at the daily dose of 4 mg/orally, with excellent results in terms of clinical response and a good safety profile. Since baricitinib does not interact with antivirals due to its prevalent renal elimination, it may be used in combination.The evidence on the advantageous action of baricitinib on viral entry and cytokine outbreak constituted the rationale to perform a trial on patients with mild to moderate COVID-19 infection receiving baricitinib combined with antiviral therapy.

Conditions

Pharmacological Action

Keywords

COVID-19; Baricitinib; Moderate disease; Infection

Outcome Measures

Primary Outcomes (1)

• The percentage of patients requiring transfer to ICU as compared with the rate of transfers observed in controls.

  The percentage of ICU admission in patients and controls will be compared for statistical difference

  2 weeks

Secondary Outcomes (1)

• The percentage of patients achieving the remission; CRP, IL-6 and TNFα values at baseline and during the treatment course; the number of AEs.

  2 weeks

Study Arms (2)

Patients

EXPERIMENTAL

All patients received baricitinib combined to antiviral therapy lopinavir/ritonavir for 2 weeks.

Drug: Baricitinib

Controls

ACTIVE COMPARATOR

All consecutive patients with mild to moderate COVID-19 infection, older than 18, a during the previous 2 weeks, who were treated with antiviral and/or hydroxychloroquine.

Drug: Baricitinib

Interventions

Baricitinib DRUG

Baricitinib 4 mg/day/orally combined to antiviral therapy ritonavir for 2 weeks. Baricitinib tablets 4 mg were administered in the morning.

Also known as: Lopinavir/Ritonavir tablets 250 mg/bid

Controls; Patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All consecutive patients with mild to moderate COVID-19 infection
• Age \>18 years,
• Clinical diagnosis of COVID19 infection
• Patients should present fever, cough and myalgia and weakness and radiological findings of pneumonia.
• All patients should be willing and able to provide written informed consent prior to performing study procedures.

You may not qualify if:

• Age less than 18
• History of thrombophlebitis.
• Patient with latent tuberculosis infection (Quantiferon test).
• Pregnancy and lactation.

Sponsors & Collaborators

• Hospital of Prato: lead

Study Sites (1)

Fabrizio Cantini

Prato, Tuscany, 59100, Italy

Location

Related Publications (9)

• Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2.

  PMID: 28466096 BACKGROUND

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

  PMID: 31978945 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 BACKGROUND

• Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

  PMID: 32187464 BACKGROUND

• 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.

  PMID: 32032529 BACKGROUND

• Bechman K, Subesinghe S, Norton S, Atzeni F, Galli M, Cope AP, Winthrop KL, Galloway JB. A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis. Rheumatology (Oxford). 2019 Oct 1;58(10):1755-1766. doi: 10.1093/rheumatology/kez087.

  PMID: 30982883 BACKGROUND

• 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.

  PMID: 32113509 BACKGROUND

• Benucci M, Damiani A, Infantino M, Manfredi M, Quartuccio L. Old and new antirheumatic drugs for the treatment of COVID-19. Joint Bone Spine. 2020 May;87(3):195-197. doi: 10.1016/j.jbspin.2020.03.013. No abstract available.

  PMID: 32321635 DERIVED

MeSH Terms

Conditions

COVID-19; Infections

Interventions

baricitinib; Lopinavir; Ritonavir; BID protein, human

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• Fabrizio Cantini, MD

  Hospital of Prato, Italy

  STUDY DIRECTOR

Central Study Contacts

Fabrizio Cantini, MD

CONTACT

+393408075607; fbrzcantini@gmail.com

Laura Niccoli, MD

CONTACT

+39 3339849690; lniccoli64@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Rheumatology Department, Principal investigator

Model Details: Patients. All consecutive patients with mild to moderate COVID-19 infection, older than 18, Patients should present fever, cough and myalgia and weakness and radiological findings of pneumonia. Controls. All consecutive patients with mild to moderate COVID-19 infection, older than 18, admitted during the previous 2 weeks, who were treated with antiviral and/or hydroxychloroquine.

Study Record Dates

• First Submitted: March 20, 2020
• First Posted: March 24, 2020
• Study Start: May 16, 2020
• Primary Completion: June 30, 2020
• Study Completion: July 30, 2020
• Last Updated: April 22, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)