Covid-19
Conditions
Keywords
COVID, SARS-CoV-2, coronavirus infections, sarilumab, IL-6 receptor inhibitors
Brief summary
The global health emergency created by the rapid spread of the SARS-CoV-2 coronavirus has pushed healthcare services to face unprecedent challenges to properly manage COVID-19 severe and critical manifestations affecting a wide population in a short period of time. Clinicians are committed to do their best with a great uncertainty in this evolving crisis. Off label use of plenty of drugs has arisen the need for clinical trials to demonstrate their true role in the therapy. Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations are available yet. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptors to inhibit IL-6 signalling, licensed in a subcutaneous route administration.
Detailed description
SARCOVID is an investigator-initiated monocentric randomised proof of concept study that aims to evaluate the efficacy and safety of a single dose of sarilumab, in subcutaneous administration, in hospitalised patients with moderate to early severe COVID-19 infection, compared to the current standard of care.
Interventions
DRUGSarilumab
Single dose treatment with sarilumab 2 x 200 mg subcutaneously
OTHERStandar of care
Usual clinical care
Sponsors
Instituto de Investigación Sanitaria Hospital Universitario de la Princesa
Maria del Rosario Garcia de Vicuña Pinedo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomised, open-label, single-center, comparative trial of sarilumab plus standard of care vs. standard of care in a 2:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age\> 18 years * Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other validated commercial or public health assay * Documented interstitial pneumonia requiring admission and at least two of the following: 1. Fever ≥ 37.8ºC (tympanic) 2. IL-6 in serum ≥ 25 ng / mL (in the absence of a previous dose of prednisone or equivalent\> 1 mg / kg) or PCR\> 5mg / dL 3. Lymphocytes \<600 mm3 4. Ferritin\> 300 mcg / L that doubles in 24 hours 5. Ferritin\> 600 mcg / L in the first determination and LDH\> 250 U / L 6. D-dimer (\> 1 mg / L) * Informed verbal or administration consent under urgent conditions, documented in the electronic medical record.
Exclusion criteria
* Patients who require mechanical ventilation at the time of inclusion. * AST / ALT values \> 5 folds upper normal limit. * Neutrophil count below 500 cells / mm3 * Platelet count below 50,000 cells / mm3 * Documented sepsis or high suspicion by pathogens other than COVID-19. * Presence of comorbidities that according to clinical judgment could lead to an unfavorable result. * Complicated diverticulitis or intestinal perforation. * Current skin infection (eg, uncontrolled dermopiodermitis). * Immunosuppressive anti-rejection therapy. * Pregnancy or lactation. * Previous treatment with tocilizumab or sarilumab. * Patients participating in some other clinical trial for SARS-CoV-2 infection. * Patients with known hypersensitivity or contraindication to sarilumab or excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of hospitalisation (days) | 30 days from enrolment | Days from the date of enrolment to the date of discharge |
| Death | 30 days from enrolment | Number of deaths |
| Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation | 7 days from enrolment | Score ranges 1-7 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 7. Not hospitalized |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to invasive mechanical ventilation (days) | 30 days from enrolment | Days from enrolment to invasive mechanical ventilation |
| Mean change in clinical status assessment using the 7-point ordinal scale at day 14 after randomisation | 14 days from enrolment | Scale ranges 1-7: 1. Death 2. Hospitalized, with mechanical ventilation or extracorporeal membrane oxygenation (ECMO). 3. Hospitalized, with non-invasive mechanical ventilation, a mask with a reservoir or oxygen with high flow nasal goggles. 4. Hospitalized with oxygen supplement 5. Hospitalized, without oxygen supplement, but in need of continued medical care (related or not with COVID) 6. Hospitalized, without oxygen supplement and without the need for continued medical care 7. Not hospitalized |
| Time to independence from supplementary oxygen therapy (days) | 30 days from enrolment | Days from enrolment to supplementary oxygen therapy withdrawal |
| Time to become afebrile (days) | 30 days from enrolment | Time to become afebrile for a minimum period of 48 hours, without antipyretics |
| Time to non-invasive mechanical ventilation (days) | 30 days from enrolment | Days from enrolment to non-invasive mechanical ventilation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of serious and non-serious adverse events. | 30 days after enrolment | Number of adverse events and number of patients with adverse events |
| Discontinuation due to adverse reactions | 30 days after enrolment | Number of adverse reactions that requires discontinuation of any drug in the study |
Countries
Spain
Outcome results
None listed