Clinical trial NCT04357808: Efficacy of Subcutaneous Sarilumab in Hospitalised Patients With Moderate-severe COVID-19 Infection (SARCOVID)
Official title: Randomized Open Pilot Study to Evaluate the Efficacy of Subcutaneous Sarilumab in Patients With Moderate-severe COVID-19 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid-19
Keywords: COVID
SARS-CoV-2
coronavirus infections
sarilumab
IL-6 receptor inhibitors
Lead sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Sponsor class: OTHER
Collaborators: name: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa
First posted: 2020-04-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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 Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations are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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation
timeFrame: 7 days from enrolment
measure: Duration of hospitalisation (days)
timeFrame: 30 days from enrolment
measure: Death
timeFrame: 30 days from enrolment
Secondary outcomes:
measure: Time to become afebrile (days)
timeFrame: 30 days from enrolment
measure: Time to non-invasive mechanical ventilation (days)
timeFrame: 30 days from enrolment
measure: Time to invasive mechanical ventilation (days)
timeFrame: 30 days from enrolment
measure: Time to independence from supplementary oxygen therapy (days)
timeFrame: 30 days from enrolment
measure: Mean change in clinical status assessment using the 7-point ordinal scale at day 14 after randomisation
timeFrame: 14 days from enrolment
Other outcomes:
measure: Incidence of serious and non-serious adverse events.
timeFrame: 30 days after enrolment
measure: Discontinuation due to adverse reactions
timeFrame: 30 days after enrolment
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
Study officials:
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: Rosario Garcia de Vicuña, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garcia-Vicuna R, Rodriguez-Garcia SC, Abad-Santos F, Bautista Hernandez A, Garcia-Fraile L, Barrios Blandino A, Gutierrez Liarte A, Alonso-Perez T, Cardenoso L, Alfranca A, Mejia-Abril G, Sanz Sanz J, Gonzalez-Alvaro I. Subcutaneous IL-6 Inhibitor Sarilumab vs. Standard Care in Hospitalized Patients With Moderate-To-Severe COVID-19: An Open Label Randomized Clinical Trial. Front Med (Lausanne). 2022 Feb 23;9:819621. doi: 10.3389/fmed.2022.819621. eCollection 2022.
citation: Garcia-Vicuna R, Abad-Santos F, Gonzalez-Alvaro I, Ramos-Lima F, Sanz JS. Subcutaneous Sarilumab in hospitalised patients with moderate-severe COVID-19 infection compared to the standard of care (SARCOVID): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Sep 9;21(1):772. doi: 10.1186/s13063-020-04588-5.