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

Phase 3

Terminated

• Conditions: Acute Respiratory Distress Syndrome (ARDS)
• Interventions: Procedure: Lung Protective Ventilation; Device: SensorMedics 3100B High Frequency Oscillatory Ventilator

• Registration Number: NCT01506401
• Lead Sponsor: Canadian Critical Care Trials Group

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2011-12-14
• Study First Submitted QC: 2012-01-09
• Study First Posted: 2012-01-10
• Status Verified: 2012-09
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Last Update Submitted: 2015-08-05
• Last Update Posted: 2015-08-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 548

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional Ventilation	Lung Protective Ventilation	Low tidal volumes, relatively high PEEP.
High Frequency Oscillation	SensorMedics 3100B High Frequency Oscillatory Ventilator	Open-lung strategy for high frequency oscillation.

Primary Outcome Measures

Name	Time	Method
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.	all-cause hospital mortality

Secondary Outcome Measures

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

Trial Locations

Locations (38)

Clinica Las Lilas; 🇨🇱 Santiago, Chile

Riyadh Armed Forces; 🇸🇦 Riyadh, Saudi Arabia

University of Western Ontario - University Hospital; 🇨🇦 London, Ontario, Canada

King Faisal Specialist Hospital & Research Centre; 🇸🇦 Jeddah, Saudi Arabia

Pontificia Universidad Catolica de Chile; 🇨🇱 Santiago, Chile

Deenanath Mangeshkar Hospital & Research Centre; 🇮🇳 Pune, India

St Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Denver Health Medical Centre; 🇺🇸 Denver, Colorado, United States

Orlando Regional Medical Centre; 🇺🇸 Orlando, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Brody School of Medicine at East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Hospital of the University ofPennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Parkland Memorial Hospital; 🇺🇸 Dallas, Texas, United States

University of Texas HSC; 🇺🇸 Houston, Texas, United States

Texas A&M HSC College of Medicine, Scott & White Hospital; 🇺🇸 Temple, Texas, United States

Peter Lougheed Centre/Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

University of Alberta Medical Centre; 🇨🇦 Edmonton, Alberta, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Vancouver Island Health Research Centre; 🇨🇦 Victoria, British Columbia, Canada

Health Sciences Centre, Winnipeg; 🇨🇦 Winnipeg, Manitoba, Canada

St. Joseph's Healthcare, McMaster University; 🇨🇦 Hamilton, Ontario, Canada

Royal Victoria Hospital; 🇨🇦 Barrie, Ontario, Canada

University of Western Ontario - Victoria Hospital; 🇨🇦 London, Ontario, Canada

Ottawa Hospital - Civic Campus; 🇨🇦 Ottawa, Ontario, Canada

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

Ottawa Hospital-General Campus; 🇨🇦 Ottawa, Ontario, Canada

St Josephs; 🇨🇦 Toronto, Ontario, Canada

St Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

University Health Network; 🇨🇦 Toronto, Ontario, Canada

Maisonneuve Rosemont; 🇨🇦 Montreal, Quebec, Canada

William Osler Health Centre; 🇨🇦 Toronto, Ontario, Canada

Patrick Bellemare; 🇨🇦 Montreal, Quebec, Canada

Centre Hosptialier de liUniersite de Montreal - CHUM- Saint Luc; 🇨🇦 Montreal, Quebec, Canada

Hopital de l'Enfant-Jesus; 🇨🇦 Quebec, Canada

Centre hospitalier universitaire de Sherbrooke (CHUS); 🇨🇦 Sherbrooke, Quebec, Canada

King Fahad National Guard Hospital; 🇸🇦 Riyadh, Saudi Arabia

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada