TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With COVID-19 Interstitial Pneumonia

Study Overview
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Brief Summary
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Multifocal interstitial pneumonia represents the most common cause of admission in intensive care units and death in SARS-CoV2 infections. In our Hospital, similarly to what reported in literature, up to 25% of admitted patients with pneumonitis requires mechanical ventilation or oro-tracheal intubation within 5-10 days. No established treatment is available for this condition. Preliminary evidence is accumulating about the efficacy of an aggressive treatment of the corona virus-induced inflammation and, in particular, investigators believe that blocking JAK1 is clinically rewarding in down-regulating IL-6 driven inflammation in patients with corona-virus infection. Thus, investigators designed a randomized controlled trial to test the hypothesis that adding Tofacitinib to the standard treatment in the early phase of COVID related pneumonitis could prevent the development of severe respiratory failure needing mechanical ventilation.

Official Title
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TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial

Conditions
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Pneumonitis, Interstitial, COVID-19

Intervention / Treatment
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* Drug: Tofacitinib
* Drug: Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SARS-CoV2 Infection diagnosed by rt-PCR CT-scan confirmed interstitial pneumonia Hospital admission from less than 24h P/F ratio >150 mmHg 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) QTc > 470 ms or >500 ms in wide QRS patients Severe History of Chronic Ischemic Heart Disease, defined as history of Major Adverse Cardiovascular Event and/or recent (one year) revascularization. History of recurrent Deep Venous Thrombosis and Pulmonary Embolism or established thrombophilic conditions (e.g. history of anti-phospholipid antibodies, …) Active Bacterial or Fungal Infection Hematological cancer Metastatic or intractable cancer Pre-existent neurodegenerative disease Severe Hepatic Impairment, History of acute diverticular disease or intestinal perforation HBsAg positive and/or HBV-DNA positive patients Severe Renal Failure (Creatinine Clearance <30ml/h) Active Herpes zoster infection Patients with active or latent TB Severe anemia (Hb<9g/dl) Lymphocyte count below 750/mcl Neutrophil count below 1000/mcl Platelet count below 50000/mcl Pregnancy or Lactation History of intolerance to the experimental drugs or excipients Degenerative maculopathy or other relevant retinal disease 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter open label randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tofacitinib+HYQ<br>Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days | Drug: Tofacitinib<br>* Jak-1/3 inhibitor<br>* Other names: Xeljanz;Drug: Hydroxychloroquine<br>* Standard Therapy<br>|
| Active Comparator: Hydroxychloroquine<br>Hydroxychloroquine 200mg cp three times a day for 14 days | Drug: Hydroxychloroquine<br>* Standard Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of severe Respiratory Failure requiring mechanical ventilation | Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150 | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of need of ICU admission | Rate of patients needing admission to the intensive care unit | 28 days | 
| Prevention of COVID-19 related Deaths | Rate of patients who die due to COVID-19 related conditions | 28 days | 
| Identification of predictors of outcome | Role of some clinical and laboratory factors in predicting outcome (Age, sex, smoking status, Body Mass Index (BMI), Comorbidities (Diabetes, number of comorbidities), Respiratory Failure at admission defined as PaO2/FiO2<300, Extension of Ct-scan involvement, basal level of serum IL-6, vW-Factor, Thrombomodulin, KL-6, sACE2 and SP-D ) | 14 days | 
| Incidence of Treatment-Emergent Adverse Events | Rate of severe drug-related adverse events | 28 days |