Clinical trial NCT04390061: TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With COVID-19 Interstitial Pneumonia
Official title: TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pneumonitis, Interstitial
COVID-19
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera Ospedali Riuniti Marche Nord
name: Ospedale Civile Santo Spirito, Pescara
name: Università Magna Grecia, Catanzaro
name: ASST Papa Giovanni XXIII, Bergamo
name: Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma
name: ASST Cremona, Cremona
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Ospedale di Circolo e Fondazione Macchi, Varese
First posted: 2020-05-15
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter open label randomized controlled trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Prevention of severe Respiratory Failure requiring mechanical ventilation
timeFrame: 14 days
Secondary outcomes:
measure: Prevention of need of ICU admission
timeFrame: 28 days
measure: Prevention of COVID-19 related Deaths
timeFrame: 28 days
measure: Identification of predictors of outcome
timeFrame: 14 days
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 28 days
Other outcomes:
Locations:
Study officials:
References: