Clinical trial NCT01506401: The Oscillation for Acute Respiratory Distress Syndrome (ARDS) Treated Early (OSCILLATE) Trial
Official title: The Oscillation for ARDS Treated Early (OSCILLATE) Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome (ARDS)
Keywords: ARDS
ventilator-induced lung injury
lung protective ventilation
high frequency oscillation
Lead sponsor: Canadian Critical Care Trials Group
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: McMaster University
name: University of Toronto
First posted: 2012-01-10
Enrollment: 548
Sex: ALL
Minimum age (years): 16
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause hospital mortality
timeFrame: 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 outcomes:
measure: Mortality at other time-points
timeFrame: Duration of hospitalization (ICU discharge, 60 days)
measure: Barotrauma
timeFrame: ICU discharge or 60 days
measure: Organ Dysfunction
timeFrame: Duration of hospitalization or 60 days
measure: Duration of mechanical ventilation
timeFrame: Duration of hospitalization or 60 days
measure: Duration of ICU & Hospital Stay
timeFrame: Duration of hospitalization which may exceed 60 days
measure: Quality of Life at 6 months
timeFrame: 6 months post randomization
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Health Medical Centre
state: Colorado
city: Orlando
country: United States
facility: Orlando Regional Medical Centre
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
city: Philadelphia
country: United States
facility: Hospital of the University ofPennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas HSC
state: Texas
city: Temple
country: United States
facility: Texas A&M HSC College of Medicine, Scott & White Hospital
state: Texas
city: Calgary
country: Canada
facility: Peter Lougheed Centre/Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: St Paul's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Vancouver Island Health Research Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre, Winnipeg
state: Manitoba
city: Barrie
country: Canada
facility: Royal Victoria Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare, McMaster University
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: University of Western Ontario - University Hospital
state: Ontario
city: London
country: Canada
facility: University of Western Ontario - Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital - Civic Campus
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital-General Campus
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: St Josephs
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: William Osler Health Centre
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Centre Hosptialier de liUniersite de Montreal - CHUM- Saint Luc
state: Quebec
city: Montreal
country: Canada
facility: Patrick Bellemare
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke (CHUS)
state: Quebec
city: Quebec
country: Canada
facility: Hopital de l'Enfant-Jesus
city: Santiago
country: Chile
facility: Clinica Las Lilas
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
city: Jeddah
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Centre
city: Riyadh
country: Saudi Arabia
facility: King Fahad National Guard Hospital
city: Riyadh
country: Saudi Arabia
facility: Riyadh Armed Forces
Study officials:
affiliation: University of Toronto
name: Niall D Ferguson, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Maureen O Meade, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.