Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID-19 Pneumonia

NCT04329650 | Completed Phase 2

• 1 other identifier: SILCOR-COVID-19
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 4

Brief Summary

In our center up to 25% of the hospitalized patients with COVID-19 progress and need an intensive care unit. It is urgent to find measures that can avoid this progression to severe stages of the disease. We hypothesize that the use of anti-inflammatory drugs used at the time they start hyperinflammation episodes could improve symptoms and prognosis of patients and prevent their progression sufficiently to avoid their need for be admitted to an Intensive Care Unit.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Proportion of patients requiring ICU admission at any time within the study period.

  29 days

Secondary Outcomes (25)

• Days of stay in the ICU during the study period.

  29 days

• Days until resolution of fever defined as body temperature (axillary ≤ 36.6 ° C, oral ≤ 37.2 ° C, or rectal or tympanic ≤ 37.8 ° C) for at least 48 hours, without administration of antipyretics or until hospital discharge.

  29 days

• Proportion of patients with a worsening requirement of supplemental oxygen at 29 days. days.

  29 days

• Days with hypoxemia (SpO2 <93% in ambient air or requiring oxygen supplemental or mechanical ventilation support) at 29 days.

  29 days

• Proportion of patients using mechanical ventilation at 29 days.

  29 days

Study Arms (2)

Siltuximab 11mg/Kg

EXPERIMENTAL

Drug: Siltuximab

Dexamethasone 6mg/24h

ACTIVE COMPARATOR

Drug: Dexamethasone

Interventions

Siltuximab DRUG

A single-dose of 11mg/Kg of siltuximab will be administered by intravenous infusion.

Siltuximab 11mg/Kg

Dexamethasone DRUG

A dose of 6mg/24 hours of dexamethasone during 10 days will be administered orally or by intravenous infusion.

Dexamethasone 6mg/24h

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old.
• Hospitalized patient (or documentation of a hospitalization plan if the patient is in an emergency department) with illness of more than 5 days of duration with evidence of pneumonia by chest radiography / tomography computed chest and meets at least one of the following requirements:
• Non-critical patient with pneumonia in radiological progression and / or
• Patient with progressive respiratory failure
• Laboratory confirmed SARS-CoV-2 infection (by PCR) or other commercialized analysis or public health in any sample collected 4 days before the randomization or COVID-19 criteria following the defined diagnostic criteria at that time in the center.
• Be willing and able to comply with the study related procedures / evaluations.
• Women of childbearing potential \* should have a negative serum pregnancy test before enrollment in the study and must commit to using methods highly effective contraceptives (intrauterine device, bilateral tubal occlusion, vasectomized couple and sexual abstinence).
• Written informed consent. In case of inability of the patient to sign the informed consent, a verbal informed consent from the legal representative or family witness (or failing this, an impartial witness outside the investigator team) will be obtained by phone.
• When circumstances so allow, participants should sign the consent form. The confirmation of the verbal informed consent will be documented in a document as evidence that verbal consent has been obtained.

You may not qualify if:

• absolute neutrophil count less than 2000 / mm3;
• AST or ALT\> 5 times the upper limit of normality;
• platelets \<50,000 per mm3.
• Patients with respiratory support greater than or equal to 60%
• In active treatment with immunosuppressants or previous prolonged treatment (more 3 months) of oral corticosteroids for a disease not related to COVID-19 at a dose greater than 10 mg of prednisone or equivalent per day.
• Known active tuberculosis or known history of tuberculosis uncompleted treatment.
• Patients with active systemic bacterial and / or fungal infections.
• Patients who have received previous treatment with IL6 inhibitor (tocilizumab, sarilumab).
• Participants who, at the investigator's discretion, are not eligible to participate, regardless of the reason, including medical or clinical conditions, or participants potentially at risk of not following study procedures.
• Patients who do not have entry criteria in the Intensive Care Unit.
• Pregnancy or lactation.
• Known hypersensitivity to siltuximab or to any of its excipients (histidine, histidine hydrochloride, polysorbate 80 and sucrose).

Sponsors & Collaborators

• Judit Pich Martínez: lead

Study Sites (4)

Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitari Mútua de Terrassa

Terrassa, Spain

Location

MeSH Terms

Conditions

COVID-19

Interventions

siltuximab; Dexamethasone

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Felipe García, MD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Manager

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 1, 2020
• Study Start: April 15, 2020
• Primary Completion: February 26, 2021
• Study Completion: February 26, 2021
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)