The Oscillation for Acute Respiratory Distress Syndrome (ARDS) Treated Early (OSCILLATE) Trial

Study Overview
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Brief Summary
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What is the effect of early high frequency oscillation (HFO) versus a lung-protective conventional ventilation (CV) strategy (using HFO only as rescue therapy), on all-cause hospital mortality among patients with severe early acute respiratory distress syndrome (ARDS)?

Detailed Description
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High frequency oscillation is theoretically ideal for lung protection. Based on a strong physiological rationale, rapidly expanding use internationally, and promising results in early small RCTS, a definitive RCT to establish the impact of HFO versus current conventional ventilation on mortality is needed. We have completed a pilot multicentre RCT in preparation for this trial, with goals of investigating patient recruitment, protocol acceptance, and crossover rates. The pilot study met all objectives including recruitment that exceeded expectations (94 patients), and very good adherence to protocol. Results of the multinational OSCILLATE Trial will establish the impact of HFO versus conventional ventilation on mortality rates among adults with severe ARDS.

Official Title
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The Oscillation for ARDS Treated Early (OSCILLATE) Trial

Conditions
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Acute Respiratory Distress Syndrome (ARDS)

Intervention / Treatment
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* Device: SensorMedics 3100B High Frequency Oscillatory Ventilator
* Procedure: Lung Protective Ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute onset of respiratory failure, with fewer than 2 weeks of new pulmonary symptoms; Endotracheal intubation or tracheostomy; Hypoxaemia - defined as a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) less than or equal to 200mmHg on FiO2 greater than or equal to 0.5, regardless of positive end expiratory pressure (PEEP) Bilateral alveolar consolidation (airspace disease) seen on frontal chest radiograph In addition, to qualify for randomization, patients are assessed on the following ventilator settings: Mode: pressure control or volume control or pressure support FiO2 greater than 0.6 (or higher if necessary to keep pulse oximetric saturation [SpO2] greater than 90%) PEEP greater than 10 cm H2O (or greater if necessary to keep SpO2 greater than 90%) Tidal volume 6 ml/kg predicted body weight (PBW) After at least 30 minutes on these settings, we sample arterial blood to assess oxygenation. If PaO2 is less than or equal to 200 mmHg, the patient qualifies for randomization; if PaO2/FiO2 greater than 200 mmHg, standardized hypoxaemia assessments are repeated at least once daily for the following 72 hours (providing eligibility criteria are still met). Exclusion Criteria: Remaining duration of mechanical ventilation less than 48 hours, as judged by the attending physician Primary cause of acute respiratory failure judged by attending physician to be circulatory overload due to, for example, congestive heart failure, hyper-resuscitation, or need for dialysis Suspected pulmonary haemorrhage syndrome Lack of commitment to ongoing life support (note that this does not include the presence of a Do Not Resuscitate order alone, if there is a commitment to ongoing life support Aged less than 16 years or greater than 85 years Weight less than 35 kg Severe chronic respiratory disease, as indicated by any of: Baseline forced expiratory volume in one second (FEV1) less than 20 ml/kg predicted body weight Pre-existing chronic interstitial lung disease with chronic interstitial infiltration on chest x-ray Documented chronic carbon dioxide (CO2) retention (partial pressure of carbon dioxide in arterial blood [PaCO2] less than 50 mmHg) and/or chronic hypoxaemia(PaO2 less than 55 mmHg on FiO2=0.21) Chronic restrictive, obstructive, neuromuscular, chest wall or pulmonary vascular disease resulting in severe exercise restriction (e.g., unable to climb stairs or perform household duties), secondary polycythaemia, severe pulmonary hypertension (mean pulmonary arterial pressure [PAP] greater than 40 mmHg), or ventilator dependency Morbid obesity - defined as greater than 1 kg/cm body height Underlying pre-existing condition with expected 6-month mortality greater than 50% Neurological conditions with risk of intracranial hypertension (where hypercapnia should be avoided) Neuromuscular disease that will result in prolonged need for mechanical ventilation, including (but not limited to): Guillain Barre syndrome Cervical spinal cord injury Previous randomization in this trial All inclusion criteria present for greater than 73 hours in study intensive care unit (ICU) On HFO at the time of screening

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Ventilation<br>Low tidal volumes, relatively high PEEP. | Procedure: Lung Protective Ventilation<br>* Tidal Volume 6ml/kg; plateau pressure < or = 35cmH20; Prescribed PEEP/FiO2 chart<br>|
| Experimental: High Frequency Oscillation<br>Open-lung strategy for high frequency oscillation. | Device: SensorMedics 3100B High Frequency Oscillatory Ventilator<br>* High Frequency Oscillation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause hospital mortality | all-cause hospital mortality | Randomised patients will be ventilated according to their assigned ventilation strategy for up to 60 days, until they die on the ventilator or are successfully (for >24 hours) liberated from mechanical ventilation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at other time-points | mortality at other time-points (ICU discharge, 60 days) | Duration of hospitalization (ICU discharge, 60 days) | 
| Barotrauma | Barotrauma | ICU discharge or 60 days | 
| Organ Dysfunction | Organ Dysfunction | Duration of hospitalization or 60 days | 
| Duration of mechanical ventilation | Duration of mechanical ventilation | Duration of hospitalization or 60 days | 
| Duration of ICU & Hospital Stay | Duration of ICU & Hospital Stay | Duration of hospitalization which may exceed 60 days | 
| Quality of Life at 6 months | Quality of Life at 6 months post randomization | 6 months post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, ventilator-induced lung injury, lung protective ventilation, high frequency oscillation