The International Nocturnal Oxygen (INOX) Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Laval University
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Yves Lacasse, Laval University
ClinicalTrials.gov Identifier:
NCT01044628
First received: January 6, 2010
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

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.

Objectives:

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.

Research plan:

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 < 70%; (2) a saturation at rest < 95% ; (3) patients fulfilling our definition of nocturnal oxygen desaturation: >=30% of the recording time with transcutaneous arterial oxygen saturation <90% on at least one of 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).


Condition Intervention
Chronic Obstructive Pulmonary Disease
Nocturnal Desaturation
Device: Concentrator
Device: Sham concentrator

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Composite outcome: all-cause mortality or requirement for continuous oxygen therapy [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 630
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)
Arms Assigned Interventions
Active Comparator: Nocturnal oxygen therapy (N-O2)
Oxygen will be delivered overnight to allow the oxygen saturation to be >90%
Device: Concentrator
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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis of COPD supported by a history of past smoking and obstructive disease: FEV1<70% predicted, FEV1/FVC<70% and a total lung capacity by body plethysmography >80% predicted;
  • Stable COPD at study entry, as demonstrated by (1) no acute exacerbation and (2) no change in medications for at least 6 weeks before enrollment in the trial;
  • Non-smoking patients for at least 6 months before enrollment in the trial;
  • SpO2 at rest < 95%;
  • Patients fulfilling the current definition of nocturnal oxygen desaturation, i.e., >=30% of the recording time with transcutaneous arterial oxygen saturation <90% on at least one of two consecutive recordings;
  • Ability ot give informed consent.

Exclusion Criteria:

  • Patients with severe hypoxemia fulfilling the usual criteria for continuous oxygen therapy at study entry: PaO2 <=55 mmHg; or PaO2 <= 59 mmHg with clinical evidence of at least one of the following: (1) with right ventricular hypertrophy (P pulmonale on ECG:3 mm leads ll, lll, aVf); (2) right ventricular hypertrophy; (3)Peripheral edema (cor pulmonale); (4) hematocrit >=55%;
  • Patients with proven sleep apnea (defined by an apnea/hypopnea index of >=15 events/hour) or suspected sleep apnea on oximetry tracings;
  • Patients currently using nocturnal oxygen therapy;
  • Patients with known left heart or congenital heart diseases, interstitial lung diseases, bronchiectasis as the main cause of obstructive disease, lung carcinoma, severe obesity (body mass index >= 40 kg/m²), or any other disease that could influence survival.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01044628

Contacts
Contact: Sarah Bernard, MSc 418-656-8711 ext 3617 sarah.bernard@criucpq.ulaval.ca
Contact: Emmanuelle Bernard, MASc 418-656-8711 ext 3610 emmanuelle.bernard@criucpq.ulaval.ca

  Show 35 Study Locations
Sponsors and Collaborators
Laval University
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Yves Lacasse, MD, MSc Laval University
  More Information

Publications:
Responsible Party: Yves Lacasse, Professeur, Laval University
ClinicalTrials.gov Identifier: NCT01044628     History of Changes
Other Study ID Numbers: MCT-99512
Study First Received: January 6, 2010
Last Updated: August 30, 2013
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by Laval University:
COPD
CANOX
Oxygen therapy
Nocturnal
Desaturation

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 23, 2014