Prevention and Early Treatment of Acute Lung Injury (PETAL) - Low Tidal Volume Universal Support Feasibility of Recruitment for Interventional Trial (LOTUS FRUIT)
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July 2016 – October 2016
July 1, 2020
Clinical Trial URLs
Primary Publication URLs
Commercial Use Data Restrictions No
Data Restrictions Based On Area Of Research No
The two main goals of PETAL-LOTUS FRUIT were to conduct a prospective, observational study within all PETAL Network sites to determine the frequency of and outcomes from acute respiratory failure and the current usual care for tidal volume ventilation in patients with and without acute respiratory distress syndrome (ARDS); and to simulate the design and power of the proposed LOTUS trial.
A previous study demonstrated improved survival among patients with ARDS receiving tidal volume (Vt) targeted to 6 ml/kg of predicted body weight (PBW). As a result, low–tidal volume ventilation (LTVV) is now recommended for all patients with ARDS, although penetration of this evidence-based practice has been limited, especially early in mechanical ventilation. LTVV may also benefit patients without ARDS. Consequently, there has been increasing call to apply LTVV for all patients with acute respiratory failure upon initiation of mechanical ventilation.
The PETAL Network considered performing a pragmatic stepped-wedge, cluster-randomized, controlled, hybrid implementation trial to examine systematic implementation of a default 6 ml/kg PBW LTVV strategy in patients with acute respiratory failure requiring intubation to improve adherence to LTVV and decrease mortality in acute respiratory failure. Trial planning may be better estimated by simulation than routine, simplistic calculations, but such simulations require detailed data of initial parameters.
The PETAL-LOTUS FRUIT study included adult patients who presented with acute respiratory failure, defined solely as those requiring invasive mechanical ventilation via an endotracheal tube who received care in the intensive care unit (ICU). Patients receiving chronic invasive mechanical ventilation through a tracheostomy, admitted to an ICU after elective surgery, presenting to the study hospital after more than 24 hours of invasive mechanical ventilation, or extubated before transfer to the ICU were excluded.
2848 patients from 49 hospitals were enrolled. Enrollment varied by hospital, ranging from 4 to 100 patients, the maximum enrollment allowed per site.
PETAL-LOTUS FRUIT was a multicenter, prospective, observational cohort study of patients with acute respiratory failure on mechanical ventilation in the PETAL Network hospitals.
For all patients, baseline demographic data, the hospital location, indication for intubation (hypoxemic or hypercapnic respiratory failure or both, altered level of consciousness, or surgery), type of ICU, and Sequential Organ Failure Assessment score in the first 24 hours after intubation were collected. Baseline ventilator data immediately after intubation, arterial blood gas results and oxygen saturation as measured by pulse oximetry, and presence of ARDS was also collected for all patients. ARDS was defined as a ratio of arterial oxygen tension to fraction of inspired oxygen (FiO2) less than or equal to 300 with a chest radiograph within 24 hours of the qualifying ratio of arterial oxygen tension to FiO2 that had bilateral infiltrates unexplained by mass, collapse, or effusion. For the first 50 patients enrolled at each hospital, daily data on ventilator mode, Vt, and presence of ARDS for the first 3 days after intubation was collected. Vt indexed to PBW was calculated from the set Vt for patients on ventilator mode with volume settings. For patients on pressure ventilation modes, Vt was calculated from the ratio of minute ventilation (in ml/min) to the respiratory rate. Enrolled patients were followed until hospital discharge or 28 days for clinical outcomes including mortality, ventilator-free days, and length of stay.
To determine the possible improvement in mortality that could be observed with a reduction in Vt from current usual care in the PETAL-LOTUS FRUIT cohort to 6 ml/kg PBW, mortality was estimated as a function of initial Vt. Five models based on data from three distinct patient populations were used. 500 simulations of a stepped-wedge, cluster-randomized clinical trial using the model with greatest predicted benefit for lowering the Vt to 6 ml/kg PBW in PETAL-LOTUS FRUIT sites were performed.
Use of initial tidal volumes less than 8 ml/kg predicted body weight was common at hospitals participating in the PETAL Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV versus usual care in acute respiratory failure, the PETAL Network deemed the proposed trial infeasible.
Lanspa MJ, Gong MN, Schoenfeld DA, et al. Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure. Ann Am Thorac Soc. 2019;16(3):356‐362. doi:10.1513/AnnalsATS.201807-459OC
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Resources AvailableStudy Datasets Only
- Data Dictionary (PDF - 208.9 KB)
- LOTIS FRUIT Annotated Case Report Forms (PDF - 790.1 KB)
- LOTUS FRUIT Protocol (PDF - 801.4 KB)
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