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

The Oscillation for ARDS Treated Early (OSCILLATE) Trial

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)?

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Procedure: Lung Protective Ventilation; Device: SensorMedics 3100B High Frequency Oscillatory Ventilator

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 Type: Interventional
• Enrollment (Actual): 548
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1J 1Z4
    • Hôpital de L'Enfant-Jésus
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Peter Lougheed Centre/Foothills Medical Centre
    • Edmonton, Alberta, Canada
      • University of Alberta Medical Centre
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Vancouver General Hospital
    • Vancouver, British Columbia, Canada
      • St Paul's Hospital
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Research Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Health Sciences Centre, Winnipeg
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare, McMaster University
    • London, Ontario, Canada, N6A 5A5
      • University of Western Ontario - University Hospital
    • London, Ontario, Canada, N6C 6B5
      • University of Western Ontario - Victoria Hospital
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital - Civic Campus
    • Ottawa, Ontario, Canada
      • Ottawa Hospital-General Campus
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada
      • University Health Network
    • Toronto, Ontario, Canada
      • St Michael's Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Science Centre
    • Toronto, Ontario, Canada, M6R 1B5
      • St Josephs
    • Toronto, Ontario, Canada
      • William Osler Health Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve Rosemont
    • Montreal, Quebec, Canada, H2X 3J4
      • Centre Hosptialier de liUniersite de Montreal - CHUM- Saint Luc
    • Montreal, Quebec, Canada, H4J 1C5
      • Patrick Bellemare
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre hospitalier universitaire de Sherbrooke (CHUS)
• Chile
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile
  • Santiago, Chile
    • Clinica Las Lilas
• India
  • Pune, India
    • Deenanath Mangeshkar Hospital & Research Centre
• Saudi Arabia
  • Jeddah, Saudi Arabia
    • King Faisal Specialist Hospital & Research Centre
  • Riyadh, Saudi Arabia
    • King Fahad National Guard Hospital
  • Riyadh, Saudi Arabia
    • Riyadh Armed Forces
• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Centre
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Regional Medical Centre
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5033
      • University of Michigan
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • Brody School of Medicine at East Carolina University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University ofPennsylvania
  • Texas
    • Dallas, Texas, United States, 75390-8558
      • Parkland Memorial Hospital
    • Houston, Texas, United States, 77030
      • University of Texas HSC
    • Temple, Texas, United States, 76508
      • Texas A&M HSC College of Medicine, Scott & White Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Canadian Critical Care Trials Group
• Collaborators: Canadian Institutes of Health Research (CIHR); McMaster University; University of Toronto
• Investigators: Principal Investigator: Niall D Ferguson, MD, MSc, University of Toronto; Principal Investigator: Maureen O Meade, MD, MSc, McMaster University

Publications and helpful links

General Publications

• Arabi YM, Cook DJ, Zhou Q, Smith O, Hand L, Turgeon AF, Matte A, Mehta S, Graham R, Brierley K, Adhikari NK, Meade MO, Ferguson ND; Canadian Critical Care Trials Group. Characteristics and Outcomes of Eligible Nonenrolled Patients in a Mechanical Ventilation Trial of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2015 Dec 1;192(11):1306-13. doi: 10.1164/rccm.201501-0172OC.
• Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD, Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; OSCILLATE Trial Investigators; Canadian Critical Care Trials Group. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013 Feb 28;368(9):795-805. doi: 10.1056/NEJMoa1215554. Epub 2013 Jan 22.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: December 14, 2011
• First Submitted That Met QC Criteria: January 9, 2012
• First Posted (Estimate): January 10, 2012

Study Record Updates

• Last Update Posted (Estimate): August 6, 2015
• Last Update Submitted That Met QC Criteria: August 5, 2015
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: ARDS; lung protective ventilation; ventilator-induced lung injury; high frequency oscillation
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: MCT94829; ISRCTN87124254 (Registry Identifier: ISRCTN)