title: Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial.
abstract: Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT.
  
  
  
  The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years.
  
  
  
  The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight.
  
  
  
  Current Controlled Trials ISRCTN50085100 ; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).
authors.affiliation: Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada. yves.lacasse@med.ulaval.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lacasse
authors.affiliation: Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bernard
authors.affiliation: Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sériès
authors.affiliation: Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada.
authors.forename: Van Hung
authors.initials: VH
authors.lastname: Nguyen
authors.affiliation: Institut thoracique de Montréal, 3650 rue St-Urbain, Montréal, Québec, H2X 2P4, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourbeau
authors.affiliation: The Ottawa Hospital - General Campus, Mailbox 211, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Shawn
authors.initials: S
authors.lastname: Aaron
authors.affiliation: Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Maltais
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D005260:Female; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010100:Oxygen / Q000097:blood*; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D011174:Portugal; D029424:Pulmonary Disease, Chronic Obstructive / Q000401:mortality* / Q000628:therapy*; D011788:Quality of Life; D012107:Research Design; D012890:Sleep; D013030:Spain
chemical_list: D010100:Oxygen
keywords: COPD; Mortality; Oxygen therapy; Randomized trial; Sleep