TOFAcitinib in SARS-CoV2 Pneumonia

Phase 2

• Conditions: SARS-COv2 Related Interstitial Pneumonia
• Interventions: Drug: Tofacitinib

• Registration Number: NCT04332042
• Lead Sponsor: Università Politecnica delle Marche

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-03-28
• Status Verified: 2020-04
• Study First Submitted QC: 2020-04-01
• Last Update Submitted: 2020-04-01
• Study First Posted: 2020-04-02
• Last Update Posted: 2020-04-02
• Study Start: 2020-04-10
• Primary Completion: 2020-06-20
• Study Completion: 2020-07-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
tofacitinib	Tofacitinib	Tofacitinib cp 5mg: 2pills twice a day for 14 days

Primary Outcome Measures

Name	Time	Method
need of mechanical ventilation	day 14	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Ospedali Riuniti di Ancona; 🇮🇹 Ancona, Marche, Italy