COVID-19, Pneumonitis, Interstitial
Conditions
Brief summary
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.
Interventions
DRUGTofacitinib
Jak-1/3 inhibitor
DRUGHydroxychloroquine
Standard Therapy
Sponsors
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Ospedale Civile Santo Spirito, Pescara
Università Magna Grecia, Catanzaro
ASST Papa Giovanni XXIII, Bergamo
Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma
ASST Cremona, Cremona
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Ospedale di Circolo e Fondazione Macchi, Varese
Università Politecnica delle Marche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter open label randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevention of severe Respiratory Failure requiring mechanical ventilation | 14 days | Rate of patients needing mechanical ventilation to maintain PaO2/FIO2\>150 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevention of need of ICU admission | 28 days | Rate of patients needing admission to the intensive care unit |
| Prevention of COVID-19 related Deaths | 28 days | Rate of patients who die due to COVID-19 related conditions |
| Identification of predictors of outcome | 14 days | 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 ) |
| Incidence of Treatment-Emergent Adverse Events | 28 days | Rate of severe drug-related adverse events |
Contacts
Primary ContactArmando Gabrielli, MD
Outcome results
None listed