Clinical trial NCT02819453: Corticosteroid Treatment for Acute Respiratory Distress Syndrome
Official title: Corticosteroid Treatment for Acute Respiratory Distress Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Respiratory Distress Syndrome
Keywords: corticosteroid
acute respiratory distress syndrome
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2016-06-30
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: adult patients diagnosed with acute respiratory distress syndrome (ARDS) based on Berlin criterion by two clinicians

Brief summary: It is acknowledged that IL-18, as a product of the inflammasome, is involved in host defence against viral and bacterial stimuli by modulating the immune response. The aim of this study was to determine IL-18 levels in serum of patients with acute respiratory distress syndrome and to investigate whether corticosteroid attenuate its levels. In addition, to explore the effect of corticosteroid therapy on the prognosis of ARDS.

Detailed description: The acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung that is characterized clinically by acute hypoxemic respiratory failure. Pathologically complex changes in the lung are manifested by an early, exudative phase followed by proliferative and fibrotic phases. Persistent ARDS is characterized by ongoing inflammation, parenchymal-cell proliferation, and disordered deposition of collagen, all of which may be responsive to corticosteroid therapy. Systemic corticosteroids have been considered a potentially beneficial therapy. However, several studies have failed to provide convincing evidence to prove the efficacy of corticosteroids in decreasing the mortality of ARDS. For the secondary outcomes, such as oxygenation improvement and reduction of the duration of mechanical ventilation, have shown consistent findings in favor of corticosteroid therapy. However, the underlying mechanisms that account for the anti-inflammatory actions of corticosteroid in ARDS patients have not yet to be elucidated, and the activities do not appear to be controlled by a single mechanism. Interleukin-18 (IL-18), along with interleukin-1b (IL-1b), is produced by inflammasomes when activated by a number of pathogen, environmental or host-derived danger signals. Inflammasomes are innate immune regulatory protein complexes which seem to play a key role in the host immune response of patients with ARDS. The aim of this study is to determine the role of steroid on IL-18 levels in serum of patients with ARDS and its effect on prognosis.

Eligibility criteria: Inclusion Criteria:

1. Able to provide written informed consent;
2. Aged 18-85 years;
3. Confirmed diagnosis of ARDS by Berlin criterion

Exclusion Criteria:

1. Active tuberculosis and disseminated fungal infection;
2. Chronic corticosteroid application
3. Patients with organ dysfunction, such as severe liver dysfunction, adrenal insufficiency, severe cardiopulmonary dysfunction;
4. Hypogammaglobulinemia or other autoimmune disease;
5. Acquired immunodeficiency syndrome;
6. Refuse to use corticosteroid;
7. Pregnant or nursing

Primary outcomes:
measure: serum IL-18 level
timeFrame: three days
measure: arterial partial pressure of oxygen/ fraction of inspired oxygen (PaO2/FiO2)
timeFrame: three days
measure: the acute physiology and chronic health evaluation (APACHE II) score
timeFrame: seven days
measure: the ratio of Neutrophils/lymphocyte
timeFrame: three days
measure: 45-day mortality after corticosteroid treatment
timeFrame: 45 days
Secondary outcomes:
measure: factors associated with the mortality of ARDS patients
timeFrame: 45 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital , Tongji University
state: Shanghai
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Jin-Fu Xu, PhD
role: STUDY_DIRECTOR
References:
citation: Dolinay T, Kim YS, Howrylak J, Hunninghake GM, An CH, Fredenburgh L, Massaro AF, Rogers A, Gazourian L, Nakahira K, Haspel JA, Landazury R, Eppanapally S, Christie JD, Meyer NJ, Ware LB, Christiani DC, Ryter SW, Baron RM, Choi AM. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med. 2012 Jun 1;185(11):1225-34. doi: 10.1164/rccm.201201-0003OC. Epub 2012 Mar 29.
citation: Yang JW, Jiang P, Wang WW, Wen ZM, Mao B, Lu HW, Zhang L, Song YL, Xu JF. The Controversy About the Effects of Different Doses of Corticosteroid Treatment on Clinical Outcomes for Acute Respiratory Distress Syndrome Patients: An Observational Study. Front Pharmacol. 2021 Jul 29;12:722537. doi: 10.3389/fphar.2021.722537. eCollection 2021.
citation: Sweeney RM, McAuley DF. Prolonged glucocorticoid treatment in acute respiratory distress syndrome - Authors' reply. Lancet. 2017 Apr 15;389(10078):1516-1517. doi: 10.1016/S0140-6736(17)30953-4. No abstract available.