TOFAcitinib in SARS-CoV2 Pneumonia

Study Overview
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Brief Summary
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Immune-mediated lung injury plays a pivotal role in severe interstitial pnemumonia related to SARS-CoV2 infection. Tofacitinib, a JAK1/3-Inhibitor, could mitigate alveolar inflammation by blocking IL-6 signal. The aim of this prospective single cohort open study is to test the hypotesis that early administration of tofacitinib in patients with symptomatic pneumonia could reduce pulmonary flogosis, preventing function deterioration and the need of mechanical ventilation and/or admission in intensive care units.

Detailed Description
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Interstitial Pneumonia is the main complication of SARS-CoV2 infection. Immune system hyperactivation, leading to alveolar inflammation, is the main mechanism in determining lung damage. Evidence are accumulating about the pivotal role played by IL-6 in this disease. Preliminary evidence, indeed, point out the efficacy of an IL-6 receptor inhibitor in improving clinical conditions in a proportion of rapidly deteriorating patients. Our hypotesis is that a precocious inhibition of IL-6 signal, by the administration of tofacitinib (JAK 1/3 Inhibitor), could hinder the progression to more severe grades of lung inflammation leading to pulmonary function deterioration. In a prospective single cohort open study, 50 patients admitted in Hospital due to SARS-CoV 2 symptomatic interstitial pneumonia, but not requiring mechanical ventilation, will be enrolled. Tofacitinb will be administered every day for 14 days, starting within 24 h from the admission. The primary outcome is to evaluate the effect of this drug on the rate of patients who will need mechanical ventilation. Safety in this population will also be actively monitored.

Official Title
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TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia

Conditions
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SARS-COv2 Related Interstitial Pneumonia

Intervention / Treatment
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* Drug: Tofacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SARS-CoV2 Infection diagnosed by rt-PCR Rx or CT-scan confirmed interstitial pneumonia Hospital admission from less than 24h Written Informed Consent Exclusion Criteria: Age <18 ys or >65 Patients in mechanical ventilation at time of admission Severe Hearth failure (NYHA 3 or 4) Severe History of Chronic Ischemic Hearth Disease, defined as history of Major Adverse Cardiovascular Event and/or recent (one year) revascularization. History of recurrent Deep Venous Thrombosis and Pulmonary Embolism Active Bacterial or Fungal Infection Hematological cancer Metastatic or intractable cancer Pre-existent neurodegenerative disease Severe Hepatic Impairment Severe Renal Failure (Creatinine Clearance <30ml/h) Active Herpes zoster infection Severe anemia (Hb<9g/dl) Lymphocyte count below 750/mcl Neutrophil count below 1000/mcl Platelet count below 50000/mcl Pregnancy or Lactation Inability to give informed consent (severe transitory or permanent mental impairment, incapacitation)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: prospective cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tofacitinib<br>Tofacitinib cp 5mg: 2pills twice a day for 14 days | Drug: Tofacitinib<br>* Tofacitinib 10mg twice a day will be administered within 24h from hospital admission for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| need of mechanical ventilation | Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150 or, if PaO2 data not available, to maintain SO2>94% with FiO2 0,5. | day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| need of admission in intensive care unit | Rate of patients needing admission to the intensive care unit for oro-tracheal intubation and/or evidence of Multiple Organ Disfunction | day 14 | 
| death | rate of patients dead | day 28 | 
| rate of adverse events | rate and type of adverse events | day 28 |