Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 11
- 主要终点
- ventilator-free days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
protective ventilation
For ARDS patients with moderate to severe mechanical ventilation(MAQUET), give 6-8ml/kg (ideal body weight PBW), and control the plateau pressure to <30cmH2O; In patients with respiratory distress, the tidal volume can be increased to 7-8ml/kg (PBW), while the plateau pressure is <30cmH2O. Adjust breathing rate according to CO2 level, up to 35 breaths/min. PBW, male: 50+0.91 (height cm-152.4); female: 45.5+0.91 (height cm-152.4).
干预措施: protective ventilation (Device)
prone position ventilation (including awake state)
For patients with moderate to severe ARDS who have no contraindications to prone ventilation, protective lung ventilation is given and prone ventilation is performed; the duration is more than 12 hours/time.
干预措施: prone position ventilation (Behavioral)
glucocorticoid therapy
Glucocorticoids are used for ARDS patients, with small doses and short courses of treatment in the acute phase (within 14 days). There is no clear recommendation for patients with ARDS from other causes. At present, the main research methods are methylprednisolone program(Solu-Medrol®), dexamethasone program, and hydrocortisone program
干预措施: glucocorticoid therapy (Drug)
inotropes therapy
For unconventional medication, according to"Surviving sepsis campaign: international guidelines for the management of sepsis and septic shock 2021".
干预措施: inotropes therapy (Drug)
restrictive fluid resuscitation
ARDS patients with circulatory or organ hypoperfusion problems should use as little fluid as possible to maintain treatment and circulation; other ARDS patients should focus on stabilizing circulation during the resuscitation phase, with controlled fluid replacement combined with early vasoactive drugs; ultrasound, Central venous pressure measurement, mixed central venous oxygen saturation, alveolar-arterial oxygen difference, blood lactate, etc. guide fluid resuscitation therapy; stop using vasoactive drugs for more than 12 hours, and use diuretics or diuretics combined with albumin to achieve fluid balance.
干预措施: restrictive fluid resuscitation (Other)
Immunomodulatory therapy
Thymosin Alpha（Thymalfasin for Injection） 1.6mg subcutaneously twice a week.
干预措施: Thymosin Alpha (Biological)
Muscle relaxant therapy
For patients with moderate to severe ARDS, if light sedation cannot achieve protective lung ventilation strategy and prone position ventilation, deep sedation combined with intermittent bolus injection of muscle relaxants（Vecuronium Bromide for Injection） is used; if protective lung ventilation strategy and prone position ventilation still cannot be achieved, deep sedation combined with continuous Inject muscle relaxants.
干预措施: Muscle relaxant therapy (Drug)
Integrated Chinese and Western Medicine Treatment
Mechanical ventilation + conventional western medicine + Dachengqi Decoction/Rhubarb-Salvia Injection/Tanreqing/Xuanbai Chengqi Decoction(Drugs determined by syndrome differentiation and treatment)
干预措施: Integrated Chinese and Western Medicine Treatment (Other)
statin therapy
There are currently two options: 1) Simvastatin （Simvastatin Tablets）80 mg QD orally for up to 28 days in patients with acute lung injury. 2) Rosuvastatin （Rosuvastatin Calcium Tablets）40 mg for the first time, followed by 20 mg orally daily for 28 days, or 3 days after being transferred out of the ICU, or after the patient died.
干预措施: statin therapy (Drug)
anti-infective treatment
Refer to the "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021." recommendations.
干预措施: anti-infective treatment (Combination Product)
Vasoactive drug therapy
According to"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".
干预措施: Vasoactive drug therapy (Drug)
Extracorporeal Membrane Oxygenation（ECMO）
ECMO (Medtronic) is chosen as rescue therapy for severe ARDS patients with refractory hypoxemia within 7 days of onset. (Oxygenation index < 50 mmHg for 3 hours, or oxygenation index < 80 mmHg for 6 hours, or arterial pH < 7.25, arterial partial pressure of carbon dioxide [Paco2] ≥ 60 mmHg > 6 hours, and respiratory rate increased to every minute 35 breaths, adjusting mechanical ventilation settings to maintain plateau pressure ≤32 cmH2O) despite ventilator optimization (defined as inspired oxygen concentration) ≥ 0.80, tidal volume 6 ml/kg (PBW), and positive end-expiratory pressure [PEEP] ≥ 10 cmH2O). V-V mode is preferred.
干预措施: Extracorporeal Membrane Oxygenation（ECMO） (Device)
stem cell therapy
Previous clinical studies have found that stem cell therapy is safe, using a single injection of bone marrow stem cells at a dose of 1, 5, 10*106 cells/kg; START trial, ClinicalTrials.gov NCT02097641, for patients with moderate to severe ARDS, a single intravenous injection of bone marrow stem cells 10* 106 cells/kg intervention protocol.
干预措施: stem cell therapy (Genetic)
Sedative analgesia/muscle relaxant therapy
For patients with moderate to severe ARDS, if light sedation cannot achieve protective lung ventilation strategy and prone position ventilation, deep sedation（Propofol Injectable Emulsion or Midazolam Injection） combined with intermittent bolus injection of muscle relaxants is used; if protective lung ventilation strategy and prone position ventilation still cannot be achieved, deep sedation combined with continuous Inject muscle relaxants（Vecuronium Bromide for Injection）.
干预措施: Sedative analgesia/muscle relaxant therapy (Drug)
结局指标
主要结局
ventilator-free days
时间窗: within 28 days
Ventilator-free days 28 days after randomization, definition: Survival without mechanical ventilation
次要结局
- 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)