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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04390061
Recruitment Status : Not yet recruiting
First Posted : May 15, 2020
Last Update Posted : May 15, 2020
Sponsor:
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
Information provided by (Responsible Party):
Armando Gabrielli, Università Politecnica delle Marche

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.

Condition or disease Intervention/treatment Phase
Pneumonitis, Interstitial COVID-19 Drug: Tofacitinib Drug: Hydroxychloroquine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter open label randomized controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: tofacitinib+HYQ
Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days
Drug: Tofacitinib
Jak-1/3 inhibitor
Other Name: Xeljanz

Drug: Hydroxychloroquine
Standard Therapy

Active Comparator: Hydroxychloroquine
Hydroxychloroquine 200mg cp three times a day for 14 days
Drug: Hydroxychloroquine
Standard Therapy




Primary Outcome Measures :
  1. Prevention of severe Respiratory Failure requiring mechanical ventilation [ Time Frame: 14 days ]
    Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150


Secondary Outcome Measures :
  1. Prevention of need of ICU admission [ Time Frame: 28 days ]
    Rate of patients needing admission to the intensive care unit

  2. Prevention of COVID-19 related Deaths [ Time Frame: 28 days ]
    Rate of patients who die due to COVID-19 related conditions

  3. Identification of predictors of outcome [ Time Frame: 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 )

  4. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 28 days ]
    Rate of severe drug-related adverse events



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04390061


Contacts
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Contact: Armando Gabrielli, MD 0712206104 a.gabrielli@staff.univpm.it

Sponsors and Collaborators
Università Politecnica delle Marche
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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Responsible Party: Armando Gabrielli, Full Professor Internal Medicine, Università Politecnica delle Marche
ClinicalTrials.gov Identifier: NCT04390061    
Other Study ID Numbers: 2020-002035-30
First Posted: May 15, 2020    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Hydroxychloroquine
Tofacitinib
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Protein Kinase Inhibitors