NCT05658692

Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1,000 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Platform adaptive embedded trial for acute respiratory distress syndrome (PETARDS) is a randomized, embedded, multifactorial, adaptive platform trial for ARDS. The study aimed to assess the impact of multiple interventions on outcomes in patients with ARDS admitted to the ICU.

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.

Conditions

• Acute Respiratory Distress Syndrome

Interventions

Type	Name	Description
DEVICE	protective ventilation	Patients with moderate to severe ARDS received ventilation treatment according to predicted body weight(PBW) and controlled plateau pressure.
BEHAVIORAL	prone position ventilation	patients with moderate to severe ARDS who don't have contraindications were given prone ventilation for over 12 hours.
DRUG	glucocorticoid therapy	Dexamethasone: Patients received intravenous dexamethasone 20 mg daily from days 1 to 5, reduced to 10 mg daily from days 6 to 10. Hydrocortisone：For septic ARDS patients, 50 mg of hydrocortisone was given as an intravenous bolus every 6 hours for 7 days; For patients with COVID-19-related ARDS, The corticosteroid field randomized participants to a fixed 7-day period of intravenous hydrocortisone (50 mg or 100 mg every 6 hours).
OTHER	restrictive fluid resuscitation	1. without other organ dysfunction patients: Minimize fluid was given; 2. other ARDS patients: In the resuscitation phase, controlled fluid replacement combined with vasoactive drugs was given; multiple measures were taken, like lactate and so on, to utilizedto guide fluid resuscitation therapy; diuretics or diuretics in combination with albumin to achieve fluid balance.
BIOLOGICAL	Thymosin Alpha	People received thymosin Alpha subcutaneous injections, twice a week.
DRUG	Muscle relaxant therapy	Deep sedation combined with intermittent bolus injection of muscle relaxant or deep sedation combined with continuous infusion of muscle relaxant
OTHER	Integrated Chinese and Western Medicine Treatment	1. ventilation; 2. conventional western medicine treatment； 3. Chinese herbal medicine（Determining medication based on syndrome differentiation）
DRUG	statin therapy	1. Simvastatin: 80mg qd po for not more than 28days; 2. Rosuvastatin: 20mg qd po (40mg for the first time) for 28days or 3 days after transfer out of the ICU, or the patient died.
COMBINATION_PRODUCT	anti-infective treatment	According to "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".
DEVICE	Extracorporeal Membrane Oxygenation（ECMO）	1. For severe ARDS patients with refractory hypoxemia within 7 days of onset; 2. (Inspiratory oxygen concentration) ≥ 0.80, tidal volume 6ml/kg (PBW), positive end-expiratory pressure \[PEEP\] ≥ 10 cmH2O; 3. V-V Model.
GENETIC	stem cell therapy	A single injection of bone marrow stem cells, doses of 1, 5, 10\*106 cells/kg was taken according to the previous clinical studies.
DRUG	Sedative analgesia/muscle relaxant therapy	Deep sedation combined with intermittent bolus injection of muscle relaxant or deep sedation combined with continuous infusion of muscle relaxant
DRUG	inotropes therapy	According to "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".
DRUG	Vasoactive drug therapy	According to "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".

Timeline

• Start date: 2022-10-01
• Primary completion: 2023-10-01
• Completion: 2023-12-01
• First posted: 2022-12-21
• Last updated: 2022-12-21

Locations

11 sites across 1 country: China