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
About this trial
This is an interventional treatment trial for Pneumonitis, Interstitial
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)
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
NCT ID
NCT04390061
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
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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