The International Nocturnal Oxygen (INOX) Trial
Background: 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 (defined as an arterial oxygen pressure [paO2] measured in stable state <=55 mmHg or in the range 56-59 mmHg when clinical evidence of pulmonary hypertension or polycythemia are noted). In Canada, LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 hours a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD. Sleep-related oxygen desaturation often occurs in patients 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. This is an attractive hypothesis and is supported by the fact that hypoxemic episodes during sleep are accompanied by substantial increases in pulmonary arterial pressure and often by important cardiac arrhythmias. Supplemental nocturnal oxygen alleviates both the acute increases in pulmonary arterial pressure and the cardiac arrhythmias. It has been suggested that, over the long run, nocturnal oxygen therapy (N-O2) may halt the progression of long-standing cor pulmonale and prolong survival. Probably due to the fact that the recommendations of scientific societies regarding the indications for and use of N-O2 in COPD not qualifying for conventional LTOT are presently imprecise, a number of patients are currently treated with N-O2 although the beneficial effects of this therapy have not been confirmed.
Primary objective: To determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether N-O2 provided for a period of 3 years decreases mortality or delay the prescription of LTOT.
Secondary objectives: To estimate, in the same population, the cost-utility ratio of nocturnal oxygen therapy over a 3-year period.
Hypotheses: In patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, N-O2 provided for a period of 3 years is effective in decreasing mortality or delaying the requirement for LTOT; and is cost-effective and favorably compares to other medical interventions.
Study design: We propose a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care in patients presenting sleep-related oxygen desaturation who do not qualify for LTOT.
Inclusion criteria: (1) patients with a diagnosis of COPD supported by an history of past smoking and obstructive disease with FEV1/FVC < 60%; (2) presence of mild-to-moderate daytime hypoxemia with a daytime paO2 in the range of 56-69 mmHg; (3) patients fulfilling our definition of nocturnal oxygen desaturation: >=30% of the recording time with transcutaneous arterial oxygen saturation <90% on two consecutive recordings.
Intervention: nocturnal oxygen therapy: N-O2 will be delivered overnight to allow the oxygen saturation to be >90%.
Placebo: The patients allocated in the control group will receive room air delivered by defective concentrator. The comparison will be double blind.
Primary outcomes: The primary outcomes of this trial are mortality from all cause or requirement for LTOT (composite outcome).
Secondary outcomes: Secondary outcomes will include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy.
Trial duration: The follow-up period lasts at least 3 years. We expect this trial to be completed within 5 years.
Sample size calculation: The sample size should give 90% chance of showing a 30% relative reduction in event rates between the two study groups (i.e., an event rate in the intervention and placebo groups of 28% and 40% respectively). We calculated that 300 patients per group are needed to complete this study (630 to account for potential withdrawal).
Chronic Obstructive Pulmonary Disease
Device: Sham concentrator
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Supportive Care
|Official Title:||Multi-Center Randomized Placebo-controlled Trial of Nocturnal Oxygen Therapy in Chronic Obstructive Pulmonary Disease. The International Nocturnal Oxygen (INOX) Trial|
- Composite outcome: all-cause mortality or requirement for continuous oxygen therapy [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: Once a year ] [ Designated as safety issue: No ]
- Health economics: Costs and health care utilization [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Nocturnal oxygen therapy (N-O2)
Oxygen will be delivered overnight to allow the oxygen saturation to be >90%
Patients allocated to the study group will receive oxygen overnight from an electrically-powered oxygen concentrator (NewLife Intensity Oxygen Concentrator, AirSep Corporation, Buffalo, NY, USA), to allow the oxygen saturation to be >90%
Placebo Comparator: Sham concentrator
Sham therapy with ambient air
Device: Sham concentrator
Patients allocated to the control group will receive ambient air delivered overnight through an electrically-powered oxygen concentrator (NewLife Intensity Oxygen Concentrator, Airsep Corporation, Buffalo, NY, USA) rendered ineffective by bypassing the sieve beds. The ineffective concentrators will have the same external appearance as the effective ones, allowing the trial to be double-blinded. We have requested approval by Health Canada in order to proceed with the modifications on the oxygen concentrators. Written permission is pending.
|Contact: Sarah Bernard, MSc||418-656-8711 ext email@example.com|
|Contact: Emmanuelle Bernard, MASc||418-656-8711 ext firstname.lastname@example.org|
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|Principal Investigator:||Yves Lacasse, MD, MSc||Laval University|