The International Nocturnal Oxygen (INOX) Trial

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2013 by Laval University.
Recruitment status was  Recruiting
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Yves Lacasse, Laval University Identifier:
First received: January 6, 2010
Last updated: August 30, 2013
Last verified: August 2013

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.

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.


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

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 identifier: NCT01044628

Contact: Sarah Bernard, MSc 418-656-8711 ext 3617
Contact: Emmanuelle Bernard, MASc 418-656-8711 ext 3610

  Hide Study Locations
Canada, Alberta
Foothill Hospital, Health Sciences Centre Withdrawn
Calgary, Alberta, Canada, T2N 4N1
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2G8
Contact: Miranda Bowen    780-407-2972   
Sub-Investigator: Eric Wong, MD         
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Lena Legkaia    604-875-4111 ext 69831   
Sub-Investigator: Jeremy Road, MD, FRCPC         
Vancouver St. Paul's Hospital Withdrawn
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Manitoba
St-Boniface General Hospital Recruiting
Winnipeg, Manitoba, Canada, R2H 2A6
Contact: Colleen Newman    204-235-3581   
Sub-Investigator: Martha Shepertycky, MD, FRCPC         
Canada, New Brunswick
Hôpital Dr Georges-L. Dumont Recruiting
Moncton, New Brunswick, Canada, E1C 2Z3
Contact: Lucille McGraw    506-382-1202   
Principal Investigator: Marcel Mallet, MD         
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre Withdrawn
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Kingston General Hospital Active, not recruiting
Kingston, Ontario, Canada, K7L 2V7
The Ottawa Hospital (General Campus) Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Gay Pratt    613-737-8899 ext 71881   
Contact: Kathy Vandemheen    613-737-8259   
Sub-Investigator: Shawn Aaron, MD         
The Ottawa Hospital (Civic Centre) Withdrawn
Ottawa, Ontario, Canada, K1Y 4E9
West Park Healthcare Centre Withdrawn
Toronto, Ontario, Canada, M6M 2J5
Canada, Quebec
Centre de la santé et des services sociaux de Laval (Cité de la Santé de Laval) Recruiting
Laval, Quebec, Canada, H7V 3Y7
Contact: Renée Daneault    450-978-8300 ext 8319   
Sub-Investigator: Bruno Paradis, MD         
Hôtel-Dieu de Lévis Recruiting
Lévis, Quebec, Canada, G6V 3Z1
Contact: Joan Morin    418-835-7121 ext 3153   
Sub-Investigator: Richard Lecours, MD         
Montreal Chest Institute Recruiting
Montreal, Quebec, Canada, H3X 2P4
Contact: Katrina Metz    514-934-1934 ext 32489   
Sub-Investigator: Jean Bourbeau, MD         
Centre Hospitalier Mount-Sinai Recruiting
Montreal, Quebec, Canada, H4W 1S7
Contact: Rima Wardini, M.Sc.    514-369-2222 ext 1681   
Principal Investigator: Marc Baltzan, MD, MSc         
Hôpital du Sacré-Coeur de Montréal Withdrawn
Montréal, Quebec, Canada, H4J 1C5
CHA-Enfant-Jésus Withdrawn
Québec, Quebec, Canada, G1J 1Z4
Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) Recruiting
Québec, Quebec, Canada, G1V 4G5
Contact: Marthe Bélanger    418-656-8711 ext 5690   
Sub-Investigator: François Maltais, MD         
Hôpital régional de Saint-Jérôme Recruiting
Saint-Jérôme, Quebec, Canada, J7Z 5T3
Contact: Marika Rousseau    450-431-8200 ext 22179   
Principal Investigator: Guy Cournoyer, MD         
CHUS, Fleurimont Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: Robert Lacasse    819-346-1110 ext 12886   
Sub-Investigator: Pierre Larivée, MD         
Centre de recherche Pneumomédic inc. Recruiting
Trois-Rivières, Quebec, Canada, G8T 7A4
Contact: Isabelle Carle    819-379-8040 ext 63373   
Principal Investigator: Christine Drapeau, MD         
Sub-Investigator: François Corbeil, MD         
CHU de Grenoble Withdrawn
Grenoble, France, BP-217-38063
Hôpital Nord de Marseille Not yet recruiting
Marseille, France, 13015
Contact: Laurie Pahus, Ph.D.   
Principal Investigator: Alain Palot, MD         
Sub-Investigator: Pascal Chanez, MD         
Groupe Hospitalier Pitié - Salpêtrière Not yet recruiting
Paris, France, 75651 Paris cedex 13
Contact: Jésus Gonzalez-Berjemo, MD   
Principal Investigator: Jésus Gonzalez-Berjemo, MD         
CHU de Poitiers Recruiting
Poitiers, France, 86000
Contact: Jean-Claude Meurice, MD   
Contact: Cécile Ingrand    +5 49 44 30 44 ext 41731   
Principal Investigator: Jean-Claude Meurice, MD         
Centro Hospitalar do Barlavento Algarvio - EPE Recruiting
Portimao, Algarve, Portugal
Contact: Nuno Carrasco   
Principal Investigator: Joao Munha, MD         
Centro Hospitalar de Coimbra Recruiting
Coimbra, Portugal
Contact: Joaquim Moita, MD   
Principal Investigator: Joaquim Moita, MD         
Centro Hospitalar da Cova da Beira Recruiting
Covilha, Portugal
Contact: Alexandre Pereira   
Principal Investigator: Salete Valente, MD         
Hospital Pulido Valente - Centro Hospitalar Lisboa Norte Recruiting
Lisboa, Portugal
Contact: Cristina Barbara, MD   
Contact: Paula Pinto, MD   
Principal Investigator: Cristina Barbara, MD         
Hospital Pedro Hispano Unidade Local de Saude de Matosinhos Recruiting
Matosinhos, Portugal
Contact: Paula Simao, MD   
Principal Investigator: Paula Simao, MD         
Centro Hospitalara Vila Nova de Gaia-Espinho EPE Recruiting
Vila Nova de Gaia, Portugal
Contact: Miguel Guimaraes, MD   
Principal Investigator: Miguel Guimaraes, MD         
Hospital Universitario de Getafe Recruiting
Getafe, Spain, 28905
Contact: Araceli Abad Fernandez, MD   
Principal Investigator: Araceli Abad Fernandez, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Javier Sayas Catalan, MD   
Principal Investigator: Javier Sayas Catalan, MD         
Complexo Hospitalario Universitario de Santiago Not yet recruiting
Santiago de Compostela, Spain, 15706
Contact: Luis Valdes Cuadrado, MD   
Principal Investigator: Luis Valdes Cuadrado, MD         
Hospital Txagorritxu Recruiting
Vitoria-Gasteiz, Spain, 01008
Contact: Jaime Marcos Cabrero   
Principal Investigator: Carlos Javier Egea Santaolalla, MD         
Sponsors and Collaborators
Laval University
Canadian Institutes of Health Research (CIHR)
Principal Investigator: Yves Lacasse, MD, MSc Laval University
  More Information

Responsible Party: Yves Lacasse, Professeur, Laval University 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:
Oxygen therapy

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases processed this record on September 03, 2015