The International Nocturnal Oxygen (INOX) Trial

NCT ID: NCT01044628

Last Updated: 2019-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2019-01-31

Brief 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.

Detailed 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.

Conditions

Chronic Obstructive Pulmonary Disease; Nocturnal Desaturation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Nocturnal oxygen therapy (N-O2)

Oxygen will be delivered overnight to the patients to allow their oxygen saturation to be \>90%

Group Type: EXPERIMENTAL

Concentrator

Intervention Type: DEVICE

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

Sham therapy with ambient air will be given to the patients at night

Group Type: SHAM_COMPARATOR

Sham concentrator

Intervention Type: DEVICE

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.

Interventions

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%

Intervention Type: 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.

Intervention Type: DEVICE

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Laval University

OTHER

Sponsor Role: lead

Responsible Party

Yves Lacasse

Professeur

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yves Lacasse, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Laval University

Locations

University of Alberta

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

St-Boniface General Hospital

Winnipeg, Manitoba, Canada

Hôpital Dr Georges-L. Dumont

Moncton, New Brunswick, Canada

Kingston General Hospital

Kingston, Ontario, Canada

The Ottawa Hospital (General Campus)

Ottawa, 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

Montreal Chest Institute

Montreal, Quebec, Canada

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Centre Hospitalier Mount-Sinai

Montreal, Quebec, 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

Hôpital Nord de Marseille

Marseille, , France

Groupe Hospitalier Pitié - Salpêtrière

Paris, , France

CHU de Poitiers

Poitiers, , France

Centro Hospitalar do Barlavento Algarvio - EPE

Portimão, Algarve, Portugal

Centro Hospitalar de Coimbra

Coimbra, , Portugal

Centro Hospitalar da Cova da Beira

Covilha, , Portugal

Hospital Pulido Valente - Centro Hospitalar Lisboa Norte

Lisbon, , Portugal

Hospital Pedro Hispano Unidade Local de Saude de Matosinhos

Matosinhos Municipality, , Portugal

Centro Hospitalara Vila Nova de Gaia-Espinho EPE

Vila Nova de Gaia, , Portugal

Hospital Galdakao-Usansolo

Galdakao, Biskaia, Spain

Hospital Universitario de Getafe

Getafe, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Txagorritxu

Vitoria-Gasteiz, , Spain

Countries

Canada; France; Portugal; Spain

References

Lacasse Y, Series 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. doi: 10.1155/2007/487831.

Reference Type: BACKGROUND

PMID: 17885694 (View on PubMed)

Lacasse Y, Series F, Corbeil F, Baltzan M, Paradis B, Simao P, Abad Fernandez A, Esteban C, Guimaraes M, Bourbeau J, Aaron SD, Bernard S, Maltais F; INOX Trial Group. Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease. N Engl J Med. 2020 Sep 17;383(12):1129-1138. doi: 10.1056/NEJMoa2013219.

Reference Type: DERIVED

PMID: 32937046 (View on PubMed)

Lacasse Y, Bernard S, Series F, Nguyen VH, Bourbeau J, Aaron S, Maltais F; International Nocturnal Oxygen (INOX) Research Group. Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial. BMC Pulm Med. 2017 Jan 9;17(1):8. doi: 10.1186/s12890-016-0343-9.

Reference Type: DERIVED

PMID: 28069009 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MCT-99512

Identifier Type: -

Identifier Source: org_study_id