The International Nocturnal Oxygen (INOX) Trial

Chronic Obstructive Pulmonary Disease Clinical Trial

— INOX  

Official title:

Multi-Center Randomized Placebo-controlled Trial of Nocturnal Oxygen Therapy in Chronic Obstructive Pulmonary Disease. The International Nocturnal Oxygen (INOX) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044628
• Other study ID #: MCT-99512
• Status: Completed
• Phase: N/A
• Start date: October 2010
• Est. completion date: January 2019

Study information

• Verified date: June 2019
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter randomized placebo controlled trial aims to determine if in patients with COPD not qualifying for LTOT but presenting significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen therapy provided for a period of 4 years decreases mortality or delay the prescription of LTOT.

Description:

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 4 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 4-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 4 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 4-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) 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 4 years. We expect this trial to be completed within 8 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Nocturnal Desaturation
• Pulmonary Disease, Chronic Obstructive

Intervention

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%
• 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.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Centre de la santé et des services sociaux de Laval (Cité de la Santé de Laval)	Laval	Quebec
Canada	Hôtel-Dieu de Lévis	Lévis	Quebec
Canada	Hôpital Dr Georges-L. Dumont	Moncton	New Brunswick
Canada	Centre Hospitalier Mount-Sinai	Montreal	Quebec
Canada	Montreal Chest Institute	Montreal	Quebec
Canada	Hôpital du Sacré-Coeur de Montréal	Montréal	Quebec
Canada	The Ottawa Hospital (General Campus)	Ottawa	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ)	Québec	Quebec
Canada	Hôpital régional de Saint-Jérôme	Saint-Jérôme	Quebec
Canada	CHUS, Fleurimont	Sherbrooke	Quebec
Canada	Centre de recherche Pneumomédic inc.	Trois-Rivières	Quebec
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	St-Boniface General Hospital	Winnipeg	Manitoba
France	Hôpital Nord de Marseille	Marseille
France	Groupe Hospitalier Pitié - Salpêtrière	Paris
France	CHU de Poitiers	Poitiers
Portugal	Centro Hospitalar de Coimbra	Coimbra
Portugal	Centro Hospitalar da Cova da Beira	Covilha
Portugal	Hospital Pulido Valente - Centro Hospitalar Lisboa Norte	Lisboa
Portugal	Hospital Pedro Hispano Unidade Local de Saude de Matosinhos	Matosinhos
Portugal	Centro Hospitalar do Barlavento Algarvio - EPE	Portimao	Algarve
Portugal	Centro Hospitalara Vila Nova de Gaia-Espinho EPE	Vila Nova de Gaia
Spain	Hospital Galdakao-Usansolo	Galdakao	Biskaia
Spain	Hospital Universitario de Getafe	Getafe
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Txagorritxu	Vitoria-Gasteiz

Sponsors (2)

Lead Sponsor	Collaborator
Laval University	Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

Canada,  France,  Portugal,  Spain, 

References & Publications (1)

Lacasse Y, Sériès F, Martin S, Maltais F. Nocturnal oxygen therapy in patients with chronic obstructive pulmonary disease: a survey of Canadian respirologists. Can Respir J. 2007 Sep;14(6):343-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite outcome: all-cause mortality or requirement for continuous oxygen therapy	Proportion of patients who died (from any cause) OR required continuous oxygen therapy	From date of randomization until the date of prescription of continuous oxygen or date of death from any cause, whichever came first, assessed up to 48 months
Secondary	Disease-specific quality of life	St-George's respiratory questionnaire; 3 domains analyzed separately : (1) symptoms; (2) activity; (3) impact. Score range for each domain: 0 - 100%; summary score: 0% (perfect health) to 100% (worst).	48 months
Secondary	Generic quality of life	Medical Outcome Survey - Short Form 36 (SF-36); 8 domains analyzed separately: (1) Physical functioning; (2) Role - physical; (3) Bodily pain; (4) General health perception; (5) Energy/vitality ; (6) Social functioning; (7) Role - emotions; (8) Mental health. Domain score and overall score: 0 to 100. Higher score = better health.	48 months
Secondary	Health economics	Costs and health care utilization	48 months