Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome

Brief Summary

Detailed Description

Mortality is significantly higher in ARDS patients requiring intensive care unit (ICU) admission. ARDS patients admitted to the ICU typically receive multiple (as many as 10 or 20) treatments that work together to fight infection, reduce pulmonary exudation, improve oxygenation, and support systemic organ function. Clinicians are often willing to choose the exact or considered safe and effective regimen from the therapies mentioned above. Still, there are individual differences in ARDS patients, and it is difficult to confirm the optimal treatment plan. It is inevitable to choose treatment without evidence-based medicine based on experience. The primary purpose of this study was to help physicians select the best-effective approach among existing ARDS therapies, and secondly to provide a rationale for specific empirical or emerging ARDS treatments. Clinical evidence to guide optimal management is best obtained from randomized controlled trials (RCTs); however, ARDS is a multi-causal, clinically and therapeutically heterogeneous clinical syndrome with rapid disease progression and complex clinical manifestations, in fact, difficult to organize RCT trials. In cases where the timing of onset and the pathophysiological mechanism cannot be determined, the initial treatment is the selection of protective ventilation/controlled infusion as the first-line standard therapy according to the Berlin classification of ARDS, and some second-line treatments with potential clinical benefit. It is difficult to conduct objective, scientific and timely evaluation, and the overall treatment plan is inevitably blind and empirical. This clinical operation mode is likely related to ARDS-related RCT research results. The results are unsatisfactory, the treatment response heterogeneity is high, and the outcome events vary greatly. closely related to the clinical status. The adaptive platform trial PETARDS is ideal for evaluating the effects of highly heterogeneous ARDS treatment strategies. This clinical research design (adaptive platform trial, APT) can use the information of patients who are participating in the study to guide the clinical treatment of subsequent newly enrolled patients. The APT trial randomized patients into multiple domains for multiple interventions to assess their effectiveness in different patients. The term "domain" refers to a common treatment unit (eg, steroid therapy) within which patients can be randomly assigned to several interventional (dose) groups (including controls, such as no steroids, as appropriate). Certainly). All trial procedures consist of a primary or "core" protocol and multiple secondary protocols, and the standard protocols, clinical treatment adaptations, and trial management and practices for specific treatment units are managed in a unified manner for each treatment unit. The core protocol, secondary protocols, and Statistical Analysis Plan (SAP) of this trial are presented in the appendix; the study required approval from the relevant ethics committees of all participating hospitals and was conducted by good clinical practice guidelines and principles described in the Declaration of Helsinki.

Primary Outcomes

Secondary Outcomes

• Duration of mechanical ventilation(within 28 days)
• ICU stay time(within 90 days)
• Organ failure free days(within 28 days)
• Health-related quality of life assessment, EQ5D-5L and WHODAS 2.0(within 6 months)
• Where the patient went after discharge(No recurrence within 90 days)
• Hospital stay(within 90 days)
• Re-admission to ICU during readmission(within 90 days)
• Days not in intensive care unit(28 days after randomization)
• All-Cause Mortality(within 28 days)
• Sequential Organ Failure Assessment (SOFA) Score(at 48 hours, 72 hours, and 7 days after randomization)
• Proportion of intubated patients undergoing tracheostomy(28 days)
• Clinical status assessment(15 days)