An Observational Study of the Use of Siltuximab (SYLVANT) in Patients Diagnosed With COVID-19 Infection Who Have Developed Serious Respiratory Complications (SISCO)

This observational study will collect data from patients treated with siltuximab program for treatment of SARS-CoV-2 infection complicated with serious respiratory complications.

This observational study will group the patients into two cohorts receiving siltuximab..

Outcome of patients will be compared to a cohort of patients receiving standard treatment without siltuximab.

The patients will be divided into 2 cohorts. Those contained in Cohort A were treated after the use of continuous positive airways pressure (CPAP) or non-invasive ventilation (NIV). Patients in Cohort B were treated after intubation

Study Overview

• Status: Completed
• Conditions: Severe Acute Respiratory Syndrome (ARDS) Secondary to SARS-COV-2 Infection
• Intervention / Treatment: Other

Detailed Description

This is a single-center observational cohort study that follows the use of treatment with siltuximab in patients with COVID-19 who have developed serious respiratory complications, defined by the need of ventilation (either invasive or non-invasive). Retrospective data collection will be carried out on those patients who have received siltuximab as a treatment for their Covid-19 and patients enrolled in ReCOVID19-2020, a retrospective study enrolling consecutive patients with a confirmed diagnosis of COVID-19 (interstitial pneumonia and positive test for SARS-COV-2) and who received standard treatment and who were hospitalized from 23 February up to 13 March 2020 at Papa Giovanni XXIII hospital.

The control cohort of the cohort study will include all the patients with pneumonia/ARDS in need of non-invasive ventilation (CPAP or NIV) or intubation and not receiving experimental treatments in the ReCOVID-19-2020.Patients that will be included will be divided into 2 cohorts, and per current estimation split in a 3:1 ratio: 75% will be in Cohort A as treated with CPAP/NIV, while 25% will form Cohort B and consists of patients in an ICU setting who are receiving mechanical ventilation.

Procedures outlined in this protocol are based on how the patients were managed as per clinicians' best judgement and best practice. No clinical procedures are required by this observational protocol. Data on the procedures already performed during the routine diagnosis and treatment of COVID-19 patients will be collected. The list of clinical and laboratory parameters is provided to direct data collection for this observational study (as available in the medical records).

During their hospitalization, patients will be monitored as per standard hospital practice or as per national (emergency) guidelines in accordance with extraordinary circumstances relating to the COVID-19 outbreak. After discharge, patients will be asked to provide (from their primary health care providers) relevant laboratory results and safety information for approximately 30 days following the start of COVID-19 treatment via ventilation (either mechanical or non-invasive).

• Study Type: Observational
• Enrollment (Actual): 220

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24127
    • ASST - Papa Giovanni XXIII

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The control cohort of the cohort study will include all the patients with pneumonia/ARDS in need of non-invasive ventilation (CPAP or NIV) or intubation and not receiving experimental treatments in the ReCOVID-19-2020.Patients that will be included into this observational study will be divided into 2 cohorts, and per current estimation split in a 3:1 ratio: 75% will be in Cohort A as treated with CPAP/NIV, while 25% will form Cohort B and consists of patients in an ICU setting who are receiving mechanical ventilation.

Description

Inclusion Criteria:

1. Clinical and radiological diagnosis of pulmonary infection by COVID-19
2. Positive microbiological evidence of SARS-CoV-2 infection
3. Diagnosis of acute respiratory distress syndrome clinical panel in accordance with Berlin 2012 criteria
4. Need of non-invasive ventilation (NIV or CPAP) or invasive ventilation (intubation)

Exclusion Criteria:

1. Active infection of bacterial or viral (non-Covid-19) origin
2. Treatment with other anti-interleukin therapy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
group 1; Patients in Cohort A were treated with siltuximab after the use of continuous positive airways pressure (CPAP) or non-invasive ventilation (NIV). Patients in Cohort B were treated after intubation
Group 2; The control cohort will include all the patients with pneumonia/ARDS in need of non-invasive ventilation (CPAP or NIV) or intubation and not receiving experimental treatments in the ReCOVID-19-2020

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality in siltuximab treated patients	The main objective of this study is to evaluate mortality in siltuximab treated patients and compare the results with the control cohort	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the need of invasive ventilation in siltuximab patients Reduction of the need of time of ventilatory support	Assess the need of invasive ventilation in siltuximab patients treated in cohort A and compare the results with the control cohort	30 days
clinical course of patients treated with siltuximab Percentage of patients that undergo to tracheostomy	Describe the clinical course of patients treated with siltuximab (Cohort A and B) in terms of ventilatory support and compare the results with the control cohort	30 days
Safety Improvement of the lung function assessed by radiologic findings	Safety of siltuximab treatment	30 days
the effect on inflammatory parameters	Evaluate the effect of siltuximab on inflammatory parameters (CRP)	30 days
Correlation of outcomes with IL-6 levels	Correlation of outcomes with IL-6 levels	30 days

Collaborators and Investigators

• Sponsor: A.O. Ospedale Papa Giovanni XXIII
• Investigators: Principal Investigator: Giuseppe GRITTI, MD, ASST Papa Giovanni XXIII

Publications and helpful links

General Publications

• ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
• Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet. 2020 Feb 22;395(10224):e35-e36. doi: 10.1016/S0140-6736(20)30305-6. Epub 2020 Feb 5. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2020
• Primary Completion (Actual): May 8, 2020
• Study Completion (Actual): May 8, 2020

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; ARDS; SARS-COV-2
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Severe Acute Respiratory Syndrome; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: v 2 22nd April 2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No