Clinical trial NCT04315480: Tocilizumab for SARS-CoV2 (COVID-19) Severe Pneumonitis
Official title: Tocilizumab (RoActemra) as Early Treatment of Patients Affected by SARS-CoV2 (COVID-19) Infection With Severe Multifocal Interstitial Pneumonia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: SARS Pneumonia
Keywords: Tocilizumab
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera Ospedali Riuniti Marche Nord
First posted: 2020-03-19
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Simon's Two-stages Optimal Design
Primary purpose: TREATMENT

Brief summary: In a Phase 2 Simon's Optimal Two-Stages Design intravenous tocilizumab will be administered as single 8mg/Kg dose in patients affected by severe multifocal interstitial pneumonia correlated to SARS-CoV2 infection. Aim of the study is to test the hypothesis that an anti-IL6 treatment can be effective in calming the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing naso-tracheal intubation and/or death.


Eligibility criteria: Inclusion Criteria:

* SARS-CoV2 Infection diagnosed by rt-PCR
* CT-scan confirmed multifocal interstitial pneumonia
* Need of oxygen therapy to maintain SO2\>93%
* Worsening of lung involvement, defined as (one of the following criteria):

  * Worsening of oxygen saturation \>3 percentage points or decrease in PaO2 \>10%, with stable FiO2 in the last 24h
  * Need of increase FiO2 in order to maintain a stable SO2 or new onset need of mechanical ventilation in the last 24h
  * Increase in number and/or extension of pulmonary areas of consolidation

Exclusion Criteria:

* Age \<18 ys and \>90 ys
* Severe heart failure
* Bacterial Infection
* Haematological neoplasm
* Neutrophil count below 1000/mcl
* Platelet count below 50000/mcl
* ALT\> x5UNL
* Inability to give informed consent

Primary outcomes:
measure: arrest in deterioration of pulmonary function
timeFrame: 7days
measure: improving in pulmonary function
timeFrame: 7 days
Secondary outcomes:
measure: need of oro-tracheal intubation
timeFrame: +7 days
measure: death
timeFrame: 14days
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Università Politecnica delle Marche
state: AN
Study officials:
References:
citation: Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol. 2020 May;15(5):700-704. doi: 10.1016/j.jtho.2020.02.010. Epub 2020 Feb 28.
citation: Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks. Pathogens. 2020 Mar 4;9(3):186. doi: 10.3390/pathogens9030186.
citation: Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2.
citation: Zumla A, Ippolito G, Ntoumi F, Seyfert-Margolies V, Nagu TJ, Cirillo D, Chakaya JM, Marais B, Maeurer M. Host-directed therapies and holistic care for tuberculosis. Lancet Respir Med. 2020 Apr;8(4):337-340. doi: 10.1016/S2213-2600(20)30078-3. Epub 2020 Feb 27. No abstract available.
citation: Sabbatinelli J, Giuliani A, Matacchione G, Latini S, Laprovitera N, Pomponio G, Ferrarini A, Svegliati Baroni S, Pavani M, Moretti M, Gabrielli A, Procopio AD, Ferracin M, Bonafe M, Olivieri F. Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients. Mech Ageing Dev. 2021 Jan;193:111413. doi: 10.1016/j.mad.2020.111413. Epub 2020 Dec 8.