Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial

Abstract

BackgroundAlthough much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality.Methods/designThis is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment.DiscussionThis study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS.Trial registrationRegistered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website (NCT01731795).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1456-4) contains supplementary material, which is available to authorized users.

An Update on Current Therapeutic Drugs Treating COVID-19

“…As a potent anti-inflammatory and anti-fibrotic drug, low doses of methylprednisolone (DEPO-Medrol or SOLU-Medrol) have the potential to prevent an extended cytokine response and may accelerate resolution of pulmonary and systemic inflammation in pneumonia [83,84]. Recently, many medical researchers believe that corticosteroids, especially methylprednisolone, may improve dysregulated immune response caused by sepsis (possible complication of infection with COVID-19) and increase blood pressure when it is low [85].…”

Diagnosis and treatment of acute pulmonary inflammation in critically ill patients: The role of inflammatory biomarkers

“…The DEXA-ARDS trial a multicenter, randomized controlled study in patients with moderate to severe ARDS persistent beyond 24 h was recently concluded and results due to be published [83] . Patients were randomized to dexamethasone 20 mg per day for 5 d followed by 10 mg per day for 5 d or placebo with ventilator-free days as primary outcome.…”

Interim Guidelines on Antiviral Therapy for COVID-19

“…Currently, there are several studies in progress to examine the efficacy of steroids for the treatment of the COVID-19 and the results should be carefully interpreted in the clinical context. Accordingly, the administration of steroids may be considered in patients with severe COVID-19 who have worsening asthma or chronic obstructive pulmonary disease, severe septic shock requiring vasopressors, and ARDS [116][117][118]. If steroids are used, the occurrence of hyperglycemia, hypernatremia, and hypokalemia should be monitored closely and corrected [116,119].…”

“…Accordingly, the administration of steroids may be considered in patients with severe COVID-19 who have worsening asthma or chronic obstructive pulmonary disease, severe septic shock requiring vasopressors, and ARDS [ 116 117 118 ]. If steroids are used, the occurrence of hyperglycemia, hypernatremia, and hypokalemia should be monitored closely and corrected [ 116 119 ].…”