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

COVID-19 Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04390061
• Other study ID #: 2020-002035-30
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2020
• Est. completion date: October 2020

Study information

• Verified date: May 2020
• Source: Università Politecnica delle Marche
• Contact: Armando Gabrielli, MD
• Phone: 0712206104
• Email: a.gabrielli[@]staff.univpm.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 116
• Est. completion date: October 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• Lung Diseases, Interstitial
• Pneumonia
• Pneumonitis, Interstitial

Intervention

Drug:
• Tofacitinib
Jak-1/3 inhibitor
• Hydroxychloroquine
Standard Therapy

Locations

Country	Name	City	State
n/a

Sponsors (9)

Lead Sponsor	Collaborator
Università Politecnica delle Marche	ASST Cremona, Cremona, ASST Papa Giovanni XXIII, Bergamo, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Ospedale Civile Santo Spirito, Pescara, Ospedale di Circolo e Fondazione Macchi, Varese, Università Magna Grecia, Catanzaro

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevention of severe Respiratory Failure requiring mechanical ventilation	Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150	14 days
Secondary	Prevention of need of ICU admission	Rate of patients needing admission to the intensive care unit	28 days
Secondary	Prevention of COVID-19 related Deaths	Rate of patients who die due to COVID-19 related conditions	28 days
Secondary	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 )	14 days
Secondary	Incidence of Treatment-Emergent Adverse Events	Rate of severe drug-related adverse events	28 days