Effects of Oxygen Supplementation During the 6-Minute Walk Test in Chronic Respiratory Failure or Exertional Hypoxemia

June 19, 2026 updated by: Istituti Clinici Scientifici Maugeri SpA

Evaluation of the Effects of the Oxygen Supplementation During 6-minute Walking Test in Patients With Chronic Respiratory Failure or Exertional Hypoxiemia

The aim of this multicenter crossover trial is to describe the effect of adding a therapeutic dose of exertional oxygen therapy, in terms of exercise performance, gas exchange, heart rate, symptoms perception and subjective easiness of performance, in a cohort of subjects hospitalized in specialized pulmonary rehabilitation centers with a diagnosis of chronic respiratory failure and/or exertional hypoxemia due to chronic obstructive pulmonary disease or interstitial lung disease.

Researchers will compare the walking performance during 6-minute walk test performed with the liters of oxygen administered as prescribed at rest (for patients with chronic respiratory failure) or in room air (for patients with exertional hypoxemia only), to the performance during a 6-minute walk test performed with the double the flow rate prescribed at rest, or with 2 L/min for patients with exertional hypoxemia only. The two tests will be performed in random order, at least 3 hours apart and no later than 24 hours apart from each other.

The main outcome will be the difference between the distance walked in the two 6-minute walk test in the two conditions. Furthermore, will be also collected and compared: the oxygen saturation and heart rate every minute, the initial and final dyspnea and fatigue, as assessed by Borg scale, and the easiness of performance through a dedicated questionnaire. The estimated sample size will be 114 patients.

This study will provide some basis for a more accurate prescription of exercise-related oxygen therapy, offering insights into the phenotype of patients who may derive the greatest benefit from this intervention. It will also stimulate discussion regarding the optimal timing and dosing of oxygen administration during exertion in patients with respiratory failure.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Although supplemental oxygen enhances acute exercise performance in COPD, its long-term impact on quality of life and mortality remains unproven. Current guidelines suggest treating exertional desaturation (SpO2<90%), but the lack of standardized titration protocols, particularly using the 6MWT, limits clinical consistency. While many patients with chronic respiratory failure (CRF) receive dual-level oxygen prescriptions (rest vs. exercise), it is unclear if this approach yields significant functional gains. Therefore, In light of these considerations, the present multicenter crossover study aims to describe the effect of adding a therapeutic dose of exertional oxygen therapy in terms of:

  1. exercise performance
  2. gas exchange
  3. heart rate
  4. symptom perception
  5. subjective easiness of performance in a cohort of patients hospitalized in specialized pulmonary rehabilitation centers with a diagnosis of chronic respiratory failure and/or exertional hypoxia due to a chronic respiratory disease at the time of discharge from an inpatient rehabilitation attempt.

As secondary aim, the study will also evaluate any difference in the response among different diseases.

This study will be conducted on subjects with chronic respiratory diseases admitted to the Pulmonary Units of the ICS Maugeri , for rehabilitation will be evaluated for inclusion in the protocol. After approval of the project by the Ethical Committee, those who meet the following criteria at the time of discharge will be enrolled in the study.

We will enroll 3 different groups of patients:

A) Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) with EH, with an exertional oxygen prescription and a PaO2 > 60mmHg breathing room air at rest; B) Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) with Chronic Respiratory Failure, with a daytime long-term oxygen therapy (LTOT) prescription and a PaO2 < 60mmHg breathing room air at rest; C) Diagnosis of Interstitial Lung Disease (ILD) with Chronic Respiratory Failure with a daytime long-term oxygen therapy (LTOT) and a PaO2 < 60mmHg breathing room air at rest.

All patients have to be in a clinically stable condition for at least one month with optimized therapy during hospitalization.

Exclusion criteria will include: presence of lung diseases other than COPD or ILD; patients requiring a resting oxygen flow rate greater than 6 L/min; patients with orthopedic, cognitive, or neurological conditions that may affect test outcomes; patients with recent cardiovascular or cerebrovascular events within the previous three months; and cognitive impairment evaluated by Mini-Mental State Examination (MMSE) score as < 25.

With a cross-over multicenter randomized design, at the time of discharge, all patients will perform two 6-Minute Walking Tests in a random order under the following conditions:

  1. O2REST: Liters of oxygen will be administered as prescribed at rest (for patients with CRF), or in room air (for patients with EH only);
  2. O2PLUS: Liters of oxygen therapy will be set at double the flow rate compared to the resting prescription, or at 2 L/min for patients with EH.

The 6MWT will be performed, according to the ATS/ERS guidelines, along a flat corridor of at least 20 meters. Each patient will receive standardized pre-test instructions and verbal encouragement at every minute during the test. The two tests will be performed at least 3 hours apart and no later than 24 hours apart from each other. All patients will perform the tests using nasal prongs and a stroller (liquid oxygen). The stroller will be either held by the patients or transported via a backpack or rollator. When patients perform the test in room air, they will carry the stroller with no oxygen supply.

The following anthropometric and clinical measures will be collected at admission: age, BMI, diagnosis, blood gas analysis (PaO2, PaCO2, pH) at rest breathing room air, time from diagnosis, time from first oxygen prescription, spirometry (FEV1, FVC, IT, RV).

The following data will be recorded during the two 6MWT tests:

  • every minute: distance walked; oxygen saturation, heart rate;
  • initial and final: blood Pressure, Borg Dyspnea Scale (BORGD), Borg Fatigue Scale (BORGF);
  • after three minutes (recovery phase): oxygen saturation, heart rate, Borg Dyspnea Scale (BORGD), Borg Fatigue Scale (BORG).

To evaluate the patient-reported easiness of performance at the end of the second test, a dedicated questionnaire will be administered.

The "oxygen response" will be the primary outcome, defined as the 6-min walk distance using supplemental oxygen (O2PLUS) minus the 6-min walk distance using O2 quantity prescribed at rest (O2REST).

The sample size calculation was done about previous literature study data on 6-minute walk distance, assuming a two-sided α level of 0.01 and a power of 90% and including a 15% dropout rate, according to the diseases: in GROUP A, a sample size of at least 41 patients will be necessary to detect a clinically relevant difference of 28 meters in 6MWD (SD 44); in GROUP B, a sample size of at least 22 patients will be necessary to detect a clinically relevant difference of 37 meters in 6MWD (SD 40); in GROUP C, a sample size of at least 50 patients will be necessary to detect a clinically relevant difference in 6MWD of 13 meters (SD 30) between the two conditions.

The data will be analyzed using STATA 12 (StataCorp, LLC) and GraphPad Prism 8 (GraphPad Software, Boston, MA, US). Baseline characteristics and outcomes will be summarized with descriptive statistics. Continuous variables will be expressed as mean ± standard deviation (SD) or median (interquartile range, IQR) if not normally distributed. Categorical variables will be presented as percentages.

Patients who increased their 6MWD by at least 30 meters due to O2_suppl. were defined as "oxygen responders". A statistical comparison between tests for paired data will be performed using paired t-tests if the variables are normally distributed, or the Wilcoxon signed-rank test if the variables are not normally distributed. The analysis will be conducted within groups, and an additional analysis will be performed by pooling the data into a single group. Furthermore, a linear regression analysis will be carried out to assess whether the changes induced by oxygen administration are associated with baseline clinical or anthropometric factors. Differences in all recorded parameters between the two conditions, both in terms of delta (change) and kinetics, will be also calculated. Statistical significance will be set at p < 0.05.

We expect to observe an improvement gap in terms of performance or symptoms in a high proportion of patients when tested under hyperoxia. However, the proportion of patients who respond to the hyperoxic stimulus, as well as the characteristics of this phenotype, remain unclear to date.

This study will provide some basis for a more accurate prescription of exercise-related oxygen therapy, offering insights into the phenotype of patients who may derive the greatest benefit from this intervention. It will also stimulate discussion regarding the optimal timing and dosing of oxygen administration during exertion in patients with respiratory failure. In practice, it will help to characterize the acute effects of oxygen administration during exertion, considering the benefits in terms of physical performance and symptom relief. Furthermore, it will support reflections on the economic and social impact of oxygen prescription, initiating a discussion on the appropriate dosing strategy for exertional oxygen therapy.

Condition or disease:

  • Chronic Respiratory Failure
  • Exertional Hypoxemia
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Interstitial Lung Disease

Intervention/treatment

  • Usual Oxygen During 6-Minute Walk Test
  • Supplemental Oxygen During 6-Minute Walk Test

Study Type

Interventional

Enrollment (Estimated)

114

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged 18 years or older
  • Diagnosis of chronic respiratory disease admitted for pulmonary rehabilitation
  • One of the following conditions at discharge:
  • Chronic obstructive pulmonary disease with exertional hypoxemia
  • Chronic obstructive pulmonary disease with chronic respiratory failure requiring long-term oxygen therapy
  • Interstitial lung disease with chronic respiratory failure requiring long-term oxygen therapy
  • Clinically stable condition for at least one month
  • Optimized medical therapy during hospitalization
  • Ability to perform the 6-minute walk test
  • Signed informed consent

Exclusion Criteria:

  • Lung diseases other than chronic obstructive pulmonary disease or interstitial lung disease
  • Resting oxygen flow requirement greater than 4 liters per minute
  • Orthopedic, neurological, or cognitive conditions that may limit walking performance
  • Recent cardiovascular or cerebrovascular events within the previous 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 6-Minute Walk Test With Usual Oxygen or Room Air (O2REST)

All participants perform the 6-minute walk test with standard oxygen flow (or room air for participants with exertional hypoxemia only). This arm represents the standard condition for comparison.

The test may be administered as first or second test, in a random order, according to the crossover design.
Other: Usual Oxygen During 6-Minute Walk Test
Participants perform the 6-minute walk test using the oxygen flow prescribed at rest for chronic respiratory failure, or room air for participants with exertional hypoxemia only. Oxygen is delivered through nasal cannula using standard equipment. Walking distance, oxygen saturation, heart rate, and symptoms are recorded during the test.
Experimental: 6-Minute Walk Test With Supplemental Oxygen (O2PLUS)

All participants perform the 6-minute walk test using a higher oxygen flow during exercise to evaluate the effects of supplemental oxygen on walking performance and symptoms.

The test may be administered as first or second test, in a random order, according to the crossover design.
Other: Supplemental Oxygen During 6-Minute Walk Test
Participants perform the 6-minute walk test using supplemental oxygen during exercise. Oxygen flow is set at double the resting prescription for participants with chronic respiratory failure, or at two liters per minute for participants with exertional hypoxemia. Oxygen is delivered through nasal cannula using standard equipment. Walking distance, oxygen saturation, heart rate, and symptoms are recorded during the test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 6-Minute Walk Distance With Supplemental Oxygen
Time Frame: Within 24 hours (during two 6-minute walk tests performed on the same day)
This outcome measures the difference in walking distance during the 6-minute walk test when participants use supplemental oxygen (O2PLUS) compared to their usual oxygen setting or room air (O2REST). The change is calculated as the distance walked with supplemental oxygen minus the distance walked with usual oxygen or room air. This outcome reflects the short-term effect of supplemental oxygen on exercise performance.
Within 24 hours (during two 6-minute walk tests performed on the same day)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oxygen Saturation During the 6-Minute Walk Test
Time Frame: During each 6-minute walk test
This outcome measures oxygen saturation levels recorded during the 6-minute walk test when participants walk with supplemental oxygen and when they walk with their usual oxygen setting or room air. Oxygen saturation is recorded every minute during the test to evaluate changes in blood oxygen levels during walking.
During each 6-minute walk test
Heart Rate During the 6-Minute Walk Test
Time Frame: During each 6-minute walk test
This outcome measures heart rate recorded during the 6-minute walk test under both oxygen conditions. Heart rate is monitored every minute during walking to assess the cardiovascular response to exercise with and without supplemental oxygen.
During each 6-minute walk test
Dyspnea Before and After the 6-Minute Walk Test
Time Frame: Before the test, immediately after the test, and 3 minutes after recovery
This outcome measures the level of dyspnea reported by participants using the Borg Dyspnea Scale before the test, immediately after the test, and three minutes after recovery. Results are compared between walking with supplemental oxygen and walking with usual oxygen or room air.
Before the test, immediately after the test, and 3 minutes after recovery
Muscles Fatigue Before and After the 6-Minute Walk Test
Time Frame: Before the test, immediately after the test, and 3 minutes after recovery
This outcome measures perceived fatigue using the Borg Fatigue Scale before the test, immediately after the test, and three minutes after recovery. Fatigue scores are compared between the two oxygen conditions.
Before the test, immediately after the test, and 3 minutes after recovery
Blood Pressure Before and After the 6-Minute Walk Test
Time Frame: Before and immediately after each 6-minute walk test
This outcome measures systolic and diastolic blood pressure assessed before and immediately after the 6-minute walk test under both oxygen conditions to monitor physiological response to exercise.
Before and immediately after each 6-minute walk test

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participant-Reported Perception of Walking Performance
Time Frame: Immediately after completion of the second 6-minute walk test
This outcome measures participants' subjective perception of their walking performance after completing both 6-minute walk tests. Participants rate perceived differences in shortness of breath, fatigue, and overall ability to walk between the two tests using a structured dedicated questionnaire.
Immediately after completion of the second 6-minute walk test

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituti Clinici Scientifici Maugeri SpA

Investigators

  • Principal Investigator: Mara Paneroni, PhD, MSc, ICS Maugeri IRCCS, Respiratory rehabilitation of the Institute of Lumezzane

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2026

Primary Completion (Estimated)

January 31, 2028

Study Completion (Estimated)

September 30, 2028

Study Registration Dates

First Submitted

March 2, 2026

First Submitted That Met QC Criteria

March 2, 2026

First Posted (Actual)

March 5, 2026

Study Record Updates

Last Update Posted (Actual)

June 23, 2026

Last Update Submitted That Met QC Criteria

June 19, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CET6L 2025-3.11/622

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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