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TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With COVID-19 Interstitial Pneumonia (TOFACoV-2)

Primary Purpose

Pneumonitis, Interstitial, COVID-19

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tofacitinib
Hydroxychloroquine
Sponsored by
Università Politecnica delle Marche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonitis, Interstitial

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    tofacitinib+HYQ

    Hydroxychloroquine

    Arm Description

    Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days

    Hydroxychloroquine 200mg cp three times a day for 14 days

    Outcomes

    Primary Outcome Measures

    Prevention of severe Respiratory Failure requiring mechanical ventilation
    Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150

    Secondary Outcome Measures

    Prevention of need of ICU admission
    Rate of patients needing admission to the intensive care unit
    Prevention of COVID-19 related Deaths
    Rate of patients who die due to COVID-19 related conditions
    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 )
    Incidence of Treatment-Emergent Adverse Events
    Rate of severe drug-related adverse events

    Full Information

    First Posted
    May 13, 2020
    Last Updated
    May 14, 2020
    Sponsor
    Università Politecnica delle Marche
    Collaborators
    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 Cà Granda, Ospedale Maggiore Policlinico, Milano, Ospedale di Circolo e Fondazione Macchi, Varese
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04390061
    Brief Title
    TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With COVID-19 Interstitial Pneumonia
    Acronym
    TOFACoV-2
    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

    2. Study Status

    Record Verification Date
    May 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    June 2020 (Anticipated)
    Primary Completion Date
    September 2020 (Anticipated)
    Study Completion Date
    October 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Università Politecnica delle Marche
    Collaborators
    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 Cà Granda, Ospedale Maggiore Policlinico, Milano, Ospedale di Circolo e Fondazione Macchi, Varese

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pneumonitis, Interstitial, COVID-19

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    Multicenter open label randomized controlled trial
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    116 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    tofacitinib+HYQ
    Arm Type
    Experimental
    Arm Description
    Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days
    Arm Title
    Hydroxychloroquine
    Arm Type
    Active Comparator
    Arm Description
    Hydroxychloroquine 200mg cp three times a day for 14 days
    Intervention Type
    Drug
    Intervention Name(s)
    Tofacitinib
    Other Intervention Name(s)
    Xeljanz
    Intervention Description
    Jak-1/3 inhibitor
    Intervention Type
    Drug
    Intervention Name(s)
    Hydroxychloroquine
    Intervention Description
    Standard Therapy
    Primary Outcome Measure Information:
    Title
    Prevention of severe Respiratory Failure requiring mechanical ventilation
    Description
    Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150
    Time Frame
    14 days
    Secondary Outcome Measure Information:
    Title
    Prevention of need of ICU admission
    Description
    Rate of patients needing admission to the intensive care unit
    Time Frame
    28 days
    Title
    Prevention of COVID-19 related Deaths
    Description
    Rate of patients who die due to COVID-19 related conditions
    Time Frame
    28 days
    Title
    Identification of predictors of outcome
    Description
    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 )
    Time Frame
    14 days
    Title
    Incidence of Treatment-Emergent Adverse Events
    Description
    Rate of severe drug-related adverse events
    Time Frame
    28 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    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)
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Armando Gabrielli, MD
    Phone
    0712206104
    Email
    a.gabrielli@staff.univpm.it

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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