Clinical trial NCT05658692: Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome
Official title: Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Respiratory Distress Syndrome
Keywords: ARDS
ICU
domain
platform adaptive embedded trial
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Renmin Hospital of Wuhan University
name: The Second Affiliated Hospital of Harbin Medical University
name: West China Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Peking Union Medical College Hospital
name: Wuhan Union Hospital, China
name: Fudan University
name: Guangdong Provincial People's Hospital
name: Ningbo No. 1 Hospital
name: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
First posted: 2022-12-21
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

Adult patients (18 years and older, regardless of gender) admitted to the ICU with ARDS; Intubation and mechanical ventilation; Moderate/severe ARDS defined by Berlin criteria (PaO2/FiO2 ≤200mmHg, PEEP ≥5cmH20); Moderate/severe ARDS less than 48 hours before randomization.

Exclusion Criteria:

Pregnancy or breastfeeding; Known allergy to the intervention drug; Daily use of an intervention drug or measure within the past 15 days; Intervention drugs or measures primarily intended to treat other conditions (eg, septic shock); Patients using the intervention drug or standard for two or more days during hospitalization; Patients are expected to die within the next 24 hours; Other: Participated in PETARDS in the past 90 days.

Primary outcomes:
measure: ventilator-free days
timeFrame: within 28 days
Secondary outcomes:
measure: Clinical status assessment
timeFrame: 15 days
measure: All-Cause Mortality
timeFrame: within 28 days
measure: Duration of mechanical ventilation
timeFrame: within 28 days
measure: Sequential Organ Failure Assessment (SOFA) Score
timeFrame: at 48 hours, 72 hours, and 7 days after randomization
measure: ICU stay time
timeFrame: within 90 days
measure: Hospital stay
timeFrame: within 90 days
measure: Organ failure free days
timeFrame: within 28 days
measure: Health-related quality of life assessment, EQ5D-5L and WHODAS 2.0
timeFrame: within 6 months
measure: Proportion of intubated patients undergoing tracheostomy
timeFrame: 28 days
measure: Where the patient went after discharge
timeFrame: No recurrence within 90 days
measure: Re-admission to ICU during readmission
timeFrame: within 90 days
measure: Days not in intensive care unit
timeFrame: 28 days after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
city: Guangdong
country: China
facility: Guangdong Provincial People's Hospital
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
city: Lanxi
country: China
facility: Lanxi People's Hospital
city: Ningbo
country: China
facility: Ningbo First Hospital
city: Shanghai
country: China
facility: Zhognshang hospital, Fudan University
city: Taizhou
country: China
facility: Taizhou Hosptial of Zhejiang Province
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Wuhan University Renmin Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Zhaocai Zhang, Doctor
role: STUDY_DIRECTOR
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