TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Enrollment
- 116
- Primary Endpoint
- Prevention of severe Respiratory Failure requiring mechanical ventilation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
tofacitinib+HYQ
Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days
Intervention: Tofacitinib (Drug)
tofacitinib+HYQ
Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days
Intervention: Hydroxychloroquine (Drug)
Hydroxychloroquine
Hydroxychloroquine 200mg cp three times a day for 14 days
Intervention: Hydroxychloroquine (Drug)
Outcomes
Primary Outcomes
Prevention of severe Respiratory Failure requiring mechanical ventilation
Time Frame: 14 days
Rate of patients needing mechanical ventilation to maintain PaO2/FIO2\>150
Secondary Outcomes
- Prevention of need of ICU admission(28 days)
- Prevention of COVID-19 related Deaths(28 days)
- Identification of predictors of outcome(14 days)
- Incidence of Treatment-Emergent Adverse Events(28 days)
Investigators
Armando Gabrielli
Full Professor Internal Medicine
Università Politecnica delle Marche