Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome

Официальное название

PREcision VENTilation to Attenuate Ventilator-Induced Lung Injury: A Phase 3 Multicenter Randomized Clinical Trial

Обзор

The goal of this interventional study is to compare standard mechanical ventilation to a lung-stress oriented ventilation strategy in patients with Acute Respiratory Distress Syndrome (ARDS). Participants will be ventilated according to one of two different strategies. The main question the study hopes to answer is whether the personalized ventilation strategy helps improve survival.

Подробное описание

ARDS is a devastating condition that places a heavy burden on public health resources. Recent changes in the practice of mechanical ventilation have improved survival in ARDS, but mortality remains unacceptably high.

This application is for support of a phase III multi-centered, randomized controlled trial of mechanical ventilation, directed by driving pressure and esophageal manometry, in patients with ARDS. The primary hypothesis is that precise ventilator titration to maintain lung stress within 0-12 centimeters of water (cm H2O), the normal physiological range experienced during relaxed breathing, will improve 60-day mortality, compared to guided usual care.

Specific Aim 1: To determine the effect on mortality of the precision ventilation strategy, compared to guided usual care, in patients with ARDS.

• Hypothesis 1: The precision ventilation strategy will decrease 60-day mortality (primary trial endpoint).

Specific Aim 2: To evaluate the effects on lung injury of the precision ventilation strategy, compared to guided usual care, in patients with ARDS.

* Hypothesis 2a: The precision ventilation strategy will improve clinical pulmonary recovery, defined using the composite endpoint alive and ventilator-free (AVF). * Hypothesis 2b: The precision ventilation strategy will attenuate alveolar epithelial injury.

Specific Aim 3: To evaluate the hemodynamic safety profile of the precision ventilation strategy, compared to guided usual care, in patients with ARDS.

• Hypothesis 3: The precision ventilation strategy will decrease hemodynamic instability, measured as shock-free days through Day 14.

Вмешательства

• Другое Precision ventilation
  The intervention arm prioritizes mitigation of ventilator-induced-lung-injury by individualizing support to patient-specific mechanics in an integrated approach to limit overdistension and atelectrauma. This is accomplished in this arm by titration of tidal volume to limitation of driving pressure at 12 centimeters of water (cmH2O) or less and using esophageal manometry to titrate PEEP to a transpulmonary pressure of 0 cmH2O with adjustments in respiratory rate to allow for permissive hypercapni
• Другое Guided usual care ventilation
  The comparison arm allows clinician discretion when titrating PEEP and tidal volume, while setting general targets for allowable PEEP/FiO2 combinations, target range for SpO2, and target range for tidal volume. This arm applies routine best-practice guidelines. This includes maintenance of tidal volumes of 6-8 cc/kg of ideal body weight, limiting plateau pressures to 30 cmH2O or less and application of PEEP-FiO2 combinations which include a wide range of typical usual care with esophageal manome

Первичные конечные точки

• 60-day mortality [Срок оценки: 60 days from randomization]

Вторичные конечные точки (4)

• 28-day mortality [Срок оценки: 28 days from randomization]
• Alive and ventilator-free through 28 days [Срок оценки: 28 days from randomization]
• Alive and Respiratory Support-Free [Срок оценки: 28 days from randomization]
• Barotrauma through Day 14 [Срок оценки: 14 days from randomization]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Ventilator-dependent ARDS, with all of the following (a-e):

• Invasive ventilation with positive end-expiratory pressure (PEEP) ≥ 8 cm H2O or FiO2 ≥ 0.5
• Hypoxemia as characterized by: • If arterial blood gas (ABG) available: the partial pressure of oxygen in the arterial blood (PaO2)/FiO2 ≤ 300 mm Hg, or, • if ABG not available OR overt clinical deterioration in oxygenation since last ABG: SpO2/FiO2 ≤ 316 with SpO2 ≤ 97% (both conditions) on two representative assessments between 1 to 6 hours apart. • If patient is positioned prone or receiving inhaled pulmonary vasodilator at time of screening:

Qualifying PaO2/FiO2 or SpO2/FiO2 (as defined above) that was recorded within the 6 hours immediately prior to initiating either of these therapies may be used for eligibility determination. • If PEEP has been increased by > 5 cm H2O within the last 12 hours immediately prior to screening:

Qualifying PaO2/FiO2 or SpO2/FiO2 (as defined above) prior to PEEP increase may be used for eligibility determination if recorded within this 12-hour window.

• Bilateral lung opacities on chest imaging not fully explained by effusions, lobar collapse, or nodules
• Respiratory failure not fully explained by heart failure or fluid overload
• Onset within 1 week of clinical insult or new/worsening symptoms
• Early in ARDS course

• Full criteria for ARDS (#2 above) first met within previous 3 days
• Current invasive ventilation episode not more than 4 days duration
• Current severe hypoxemic episode (receipt of invasive ventilation, noninvasive ventilation, or high-flow nasal cannula) not more than 10 days duration

Критерии исключения

• Esophageal manometry already in use clinically
• Severe brain injury: including suspected elevated intracranial pressure, cerebral edema, or Glasgow coma score (GCS) ≤ 8 directly caused by severe brain injury (e.g., ischemia or hemorrhage)
• Gross barotrauma or chest tube inserted to treat barotrauma (note: chest tube inserted strictly for drainage of pleural effusion is not an exclusion)
• Esophageal pathology that, in judgement of the site investigator, significantly increases risk of esophageal catheter placement, including high-risk esophageal varices, recent oropharyngeal or gastroesophageal surgery; or past esophagectomy
• Ongoing severe coagulopathy (platelet < 5000/μL or INR > 4)
• Extracorporeal membrane oxygenation (ECMO) or CO2 removal (ECCO2R)
• Neuromuscular disease that impairs spontaneous breathing (including but not limited to amyotrophic lateral sclerosis, Guillain-Barré syndrome, spinal cord injury at C5 or above)
• Any of the following severe chronic lung diseases: cystic fibrosis, acute bronchiectasis exacerbation, acute exacerbation of a chronic interstitial lung disease (ILD), chronic pulmonary hypertension (PH) on PH-targeted vasoactive medication, or lung transplant
• End-stage chronic cirrhosis with Child-Pugh Class C (Section 12.3)
• ICU admission for burn injury
• Current ICU stay > 2 weeks or acute care hospital stay > 4 weeks
• Moribund patient not expected to survive 24 hours as assessed by the study physician; if cardiopulmonary resuscitation (CPR) was provided, assessment for moribund status must occur at least 6 hours after CPR was completed
• Current limitation on life-sustaining care (other than do-not-resuscitate), or expectation by clinical team that a limitation on life-sustained care will be adopted within next 24 hours.
• Treating clinician refusal or unwilling to use protocol-specified ventilator settings/modes
• Prisoner
• Previous enrollment in this trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 33 центра

• University of Arizona — Tucson
• University of Arkansas for Medical Sciences — Little Rock
• University of California, San Diego — La Jolla
• University of California, Los Angeles Medical Center — Los Angeles
• Cedar-Sinai Medical Center — Los Angeles
• Stanford University — Palo Alto
• University of California, San Francisco — San Franciso
• University of Miami — Miami
• … и ещё 25 центров

Публикации

• Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2 PMID 30776290
• National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 1 PMID 31112383

Идентификаторы

NCT: NCT06066502 · 2023P000682 · 1U24HL166784 · 1UG3HL166785

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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