Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Niall Ferguson


Contact details

Toronto Western Hospital
399 Bathurst St.
M5T 2S8
+1 (0)416 603 6203



Additional contact

Dr Maureen Meade


Contact details

McMaster University
Faculty of Health Sciences
Department of Clinical Epidemiology & Biostatistics
1200 Main St W
L8N 3Z5
+1 (0)905 525 9140 ext. 22160

Additional identifiers

EudraCT number number


Protocol/serial number


Study information

Scientific title

High frequency oscillation versus best current conventional ventilation to reduce acute respiratory distress syndrome (ARDS) mortality: a multicentre randomised controlled trial



Study hypothesis

What is the effect of early high frequency oscillation (HFO) versus best current conventional ventilation (CV) using HFO only as rescue therapy, on all-cause hospital mortality among patients with severe early acute respiratory distress syndrome (ARDS)?

Ethics approval

1. University Health Network (University of Toronto) - approval pending as of 11/05/2009
2. Hamilton Health Sciences (McMaster University) - approval pending as of 11/05/2009
All other centres will seek ethics approval before recruiting participants.

Study design

Multicentre randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Acute respiratory distress syndrome (ARDS)


Intervention group: high frequency oscillatory (HFO) ventilation using a lung-open approach and an explicit protocol.
Control group: conventional ventilation using low tidal volumes, a lung-open approach and an explicit protocol, and utilising HFO only as true rescue therapy.

Intervention type



Drug names

Primary outcome measures

All-cause in-hospital mortality

Secondary outcome measures

1. Mortality at other time-points (ICU discharge, 28-day)
2. Barotrauma
3. Organ dysfunction
4. Duration of mechanical ventilation
5. Duration of ICU and hospital stay
6. Quality of life at 6 months

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Acute onset of respiratory failure, with fewer than 2 weeks of new pulmonary symptoms
2. Endotracheal intubation or tracheostomy
3. Hypoxaemia - defined as a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) less than or equal to 200 mmHg on FiO2 greater than or equal to 0.5, regardless of positive end expiratory pressure (PEEP)
4. Bilateral alveolar consolidation (airspace disease) seen on frontal chest radiograph
5. Aged 16 years or over, either sex. No upper age limit.

In addition, to qualify for randomisation, patients are assessed on the following ventilator settings:
6. Mode: pressure control or volume control or pressure support
7. FiO2 greater than 0.6 (or higher if necessary to keep pulse oximetric saturation [SpO2] greater than 90%)
8. PEEP greater than 10 cm H2O (or greater if necessary to keep SpO2 greater than 90%)
9. 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 randomisation; if PaO2/FiO2 greater than 200 mmHg, standardised hypoxaemia assessments are repeated at least once daily for the following 72 hours (providing the eligibility criteria are still met).

Participant type


Age group




Target number of participants

1200 (actual number recruited by end of recruitment: 548)

Participant exclusion criteria

1. Remaining duration of mechanical ventilation less than 48 hours, as judged by the attending physician
2. 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
3. Suspected pulmonary haemorrhage syndrome
4. 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)
5. Aged less than 16 years
6. Weight less than 35 kg
7. Severe chronic respiratory disease, as indicated by any of:
7.1. Baseline forced expriatory volume in one second (FEV1) less than 20 ml/kg predicted body weight
7.2. Pre-existing chronic interstitial lung disease with chronic interstitial infiltration on chest X-ray
7.3. 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)
7.4. 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 artery pressure [PAP] greater than 40 mmHg), or ventilator dependency
8. Morbid obesity - defined as greater than 1 kg/cm body height
9. Underlying pre-existing condition with expected 6-month mortality greater than 50%
10. Neurological conditions with risk of intracranial hypertension (where hypercapnia should be avoided)
11. Neuromuscular disease that will result in prolonged need for mechanical ventilation, including (but not limited to):
11.1. Guillain Barré syndrome
11.2. Cervical spinal cord injury
12. Previous randomisation in this trial
13. All inclusion criteria present for greater than 72 hours in study intensive care unit (ICU)
14. On HFO at the time of screening

Recruitment start date


Recruitment end date



Countries of recruitment

Canada, Chile, France, Germany, India, Saudi Arabia, Singapore, Spain, United Kingdom, United States of America

Trial participating centre

Toronto Western Hospital
M5T 2S8

Sponsor information


Canadian Critical Care Trials Group (Canada)

Sponsor details

c/o Dr. John Marshall
St. Michael's Hospital
M5M 27K

Sponsor type

Research organisation



Funder type

Research organisation

Funder name

Canadian Institutes of Health Research

Alternative name(s)

Instituts de recherche en santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government



Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2013 results in

Publication citations

  1. Results

    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, , , High-frequency oscillation in early acute respiratory distress syndrome., N. Engl. J. Med., 2013, 368, 9, 795-805, doi: 10.1056/NEJMoa1215554.

Additional files

Editorial Notes