Sarilumab versus standard of care for the early treatment of COVID-19 pneumonia in hospitalized patients: SARTRE: a structured summary of a study protocol for a randomised controlled trial

• Published in: Current controlled trials in cardiovascular medicine 2020-09, Vol.21 (1), p.794-3, Article 794
• Main Authors: Caballero Bermejo, Antonio F, Ruiz-Antorán, Belén, Fernández Cruz, Ana, Diago Sempere, Elena, Callejas Díaz, Alejandro, Múñez Rubio, Elena, Avendaño-Solá, Cristina, Ramos Martínez, Antonio, Sancho López, Aránzazu
• Format: Article
• Language: English
• Subjects: Adult; anti-IL6 inhibitor; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Bacterial pneumonia; Betacoronavirus - drug effects; Betacoronavirus - isolation & purification; Care and treatment; Clinical Trials, Phase II as Topic; Coronavirus Infections - drug therapy; Coronavirus Infections - immunology; Coronavirus Infections - physiopathology; Coronaviruses; COVID-19; Cytokine Release Syndrome - immunology; Cytokine Release Syndrome - prevention & control; Female; Humans; Letter; Male; Pandemics; Pneumonia; Pneumonia, Viral - diagnosis; Pneumonia, Viral - drug therapy; Pneumonia, Viral - etiology; Pneumonia, Viral - immunology; Pneumonia, Viral - physiopathology; protocol; Randomised controlled trial; Randomized Controlled Trials as Topic; Receptors, Interleukin-6 - antagonists & inhibitors; sarilumab; SARS-CoV-2; Steroids; Treatment Outcome; Ventilation; Ventilators
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-020-04633-3

In some patients, acute, life-threatening respiratory injury produced by viruses such as SARS-CoV and other viral pneumonia are associated with an over-exuberant cytokine release. Elevated levels of blood IL-6 had been identified as a one of the risk factors associated with severe COVID-19 disease. Anti-IL6 inhibitors are among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. At present, their use is prioritized to patients with severe interstitial pneumonia (Brescia-COVID Scale-COVID 2-3) with hyperinflammation as determined by the presence of elevated IL6 and/or d-dimer, or progressive d-dimer increase, in patients who otherwise are subsidiary to ICU admission. However, many uncertainties remain on the actual role of anti-IL6 inhibitors in this setting, and whether current use and timing is the right one. There is the hypothesis that the use of anti-IL6 inhibitors at an earlier state during the hyperinflammatory syndrome would be beneficial and may avoid progressing to ARDS. On the other hand, the standard of care has changed and nowadays the use of corticosteroids has become part of the SOC in the treatment of COVID-19 pneumonia. Our limited experience suggests that better treatment outcomes can be achieved when combining IL6-inhibitors (e.g. sarilumab) with corticosteroids. The aim of the present study is to evaluate if an earlier therapeutic intervention with sarilumab plus SOC (including corticosteroids) may be more effective than current standard of care alone, in preventing progression to respiratory failure in COVID-19 infected patients with interstitial pneumonia. This study will also provide supportive evidence to that provided by currently ongoing studies on the efficacy and safety of sarilumab in this clinical context. A phase two multi-center randomised controlled trial (RCT) with two parallel arms (1:1 ratio). They will be hospitalized patients, of at least 18 years of age, with severe COVID-19 who have positive RT-PCR test and have radiographic evidence of pulmonary infiltrates by imaging or rales/crackles on exam and SpO2 ≤ 94% on room air that requires supplemental oxygen. Patients must present elevation of inflammatory parameters (IL-6 > 40 pg/mL or d-dimer >1.0 mcg/ml) or, alternatively, progressive worsening in at least two of these inflammatory parameters in the prior 24-48h: CRP, LDH, serum ferritin, lymphopenia, or d-dime