Long-term Oxygen Treatment Trial

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is a serious respiratory disease in which the airways in the lungs are partially blocked, resulting in symptoms of chest tightness, coughing, and difficulty breathing. Currently, there are many available treatments for managing COPD symptoms and improving quality of life, including medications, lifestyle changes, oxygen therapy, and pulmonary rehabilitation. For people with severe COPD that is characterized by very low blood oxygen levels at rest, long term oxygen therapy can help to prolong life and promote feelings of well-being. However, the effectiveness of supplemental oxygen therapy for people with COPD that is characterized by only moderately low blood oxygen levels at rest or normal blood oxygen at rest and desaturation on exercise is not known. This study will evaluate the effectiveness of supplemental oxygen therapy in treating people with COPD who have moderately low blood oxygen levels at rest or who have normal blood oxygen levels at rest, but have low or very low blood oxygen levels during exercise.

Detailed Description
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COPD is the fourth leading cause of death in the United States, with more than 12 million people currently diagnosed with the disease. Risk factors for COPD include smoking, environmental exposure to lung irritants, and genetic predisposition. People with COPD often experience symptoms of chronic cough, shortness of breath, excess mucus production, and wheezing. In COPD, the airways in the lungs are chronically obstructed, and if left untreated, this obstruction can cause significant damage to the lungs and lasting disability. The quality of life of a person with COPD decreases as the disease progresses, making treating and managing COPD in the moderate stages important. Long-term oxygen therapy has been shown to help people with severe COPD that is characterized by very low blood oxygen levels at rest to live longer and healthier lives. This study will determine whether supplemental oxygen therapy is helpful for people with COPD that is characterized by moderately low blood oxygen levels at rest or normal oxygen levels at rest and low or very low levels during exercise. Participation in this study will last at least one year and up to 7 years. Potential participants will first undergo a screening visit that will include questionnaires, a breathing test, measurements of resting and walking blood oxygen levels, a brief physical exam, and a blood draw. Eligible participants will then return for a second screening visit, during which they will complete more questionnaires. At the end of the second visit, eligible participants will be assigned randomly to supplemental oxygen therapy or no oxygen therapy. Participants assigned to supplemental oxygen therapy will receive stationary and portable oxygen systems. Shortly after receiving the portable oxygen system, participants will return for a 1-hour visit to determine how much oxygen to use while walking and to learn how to use the equipment. Participants who have low blood oxygen levels during rest will be instructed to use supplemental oxygen 24 hours per day. Patients with normal resting blood oxygen levels, but low or very low blood oxygen levels during exercise will be instructed to use it during physical activity and sleep. Throughout the treatment period, participants will be asked to keep records of the number of oxygen tanks emptied or pounds of oxygen delivered, meter readings, and changes in equipment. Study officials will contact participants weekly for the first month, monthly for the next 5 months, and then every 2 months until the Year 1 study visit. Participants will also complete a form about their oxygen equipment and usage every 2 months. Participants assigned to receive no oxygen treatment will be contacted 1 week after study group assignment for a check-up. All participants will return for study visits once a year for up to 7 years. At each of these visits, participants will complete some of the same tests and questionnaires from the screening visit. At the Year 1 visit, participants will also undergo a blood draw. Both treatment groups will receive two phone calls each year to check on status and use of oxygen. Participants in both groups will be asked to complete a quality of life questionnaire by mail at 4 months and 16 months. Participants will also sign a release of medical records form each year and will have their Medicare claims collected for the time they are in the study.

Official Title
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Effectiveness of Long-term Oxygen Therapy in Treating People With Chronic Obstructive Pulmonary Disease With Moderate Desaturation

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Supplemental oxygen therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at least 40 years COPD Dyspnea, determined by Modified Medical Research Council (MMRC) scale of at least 1 Dyspnea and lung disease process dominated by COPD in judgment of the study physician Participant must meet one of the following: Post-bronchodilator forced expiratory volume in 1 second (FEV1) percent less than or equal to 70% predicted Post-bronchodilator forced expiratory volume in 1 second (FEV1) percent >70% predicted and LOTT study physician determines that there is radiologic evidence of emphysema Post-bronchodilator FEV1/forced vital capacity (FVC) less then 0.70 Participant must meet either of the following oxygen saturation criteria: Oxygen saturation of at least 89% and no greater than 93% after sitting quietly on room air, without hyperventilation and without pursed lips breathing during oximetry Resting oxygen saturation 94% or greater and desaturation during exercise defined as saturation below 90% for at least 10 seconds during the 6 minute walk test If participant is on supplemental oxygen at the start of screening, all of the following must be met prior to randomization: Participant agrees to stop using oxygen if randomized to no oxygen Participant's physician agrees in writing to rescind order for oxygen if participant is randomized to no oxygen Participant must report not using oxygen on the day of randomization and must report not using oxygen for the 4 calendar days prior to randomization Satisfactory resolution of logistics of continuation with same oxygen company with waiver of cost sharing obligations or switch to new company that will waive cost sharing obligations if participant is randomized to oxygen At least 10 pack-years of tobacco cigarette smoking before study entry Agreement not to smoke while using supplemental oxygen Medicare beneficiary with both Part A and Part B coverage or insurance OR personally willing to cover costs typically covered by Medicare Approval of study physician for randomization to either treatment group Completion of all required prerandomization assessments within 60 days of initiating study entry Randomization within 60 days of initiating eligibility evaluation Consent Exclusion Criteria: Less than 30 days post treatment for acute exacerbation of COPD as of initiating eligibility evaluation (less than 30 days from last dose of antibiotics or since a new or increased dose of systemic corticosteroids was initiated); chronic use of systemic corticosteroids while health is stable is not exclusionary COPD exacerbation requiring antibiotics, new or increased dose of systemic corticosteroids, or oxygen treatment after screening starts and prior to randomization (chronic use of corticosteroids while health is stable is not exclusionary) Less than 30 days post discharge from an acute care hospital after acute care hospitalization for COPD or other condition, as of initiating eligibility evaluation (participant may be in a rehab hospital at time of screening) New prescription of supplemental oxygen after screening starts and before randomization Thoracotomy, sternotomy, major cardiopulmonary intervention (e.g., lung resection, open heart surgery, etc.), or other procedure in the 6 months before study entry likely to cause instability of pulmonary status Non-COPD lung disease that affects oxygenation or survival Epworth Sleepiness Scale score greater than 15 Desaturation below 80% for at least 1 minute during the 6-minute walk test Disease or condition expected to cause death, inability to perform procedures for the trial, or inability to comply with therapy within 6 months of random assignment, as judged by the study physician Participation in another intervention study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supplemental oxygen therapy<br>Participants will receive treatment with supplemental oxygen therapy. | Drug: Supplemental oxygen therapy<br>* Oxygen dose at rest and during sleep will be 2 L/min via nasal cannula. The oxygen dose used while walking will be individually prescribed and will be sufficient to maintain oxygen saturation at 90% or above for at least 2 minutes while walking. Participants who have low blood oxygen levels at rest will be instructed to use oxygen 24 hours per day. Participants who have normal resting blood oxygen levels, but low or very low blood oxygen levels during exercise, will be instructed to use oxygen during physical activity and sleep.<br>|
| No Intervention: No supplemental oxygen therapy<br>Participants will receive no supplemental oxygen therapy, unless the participant becomes severely hypoxemic at rest (e.g., meets conventional Medicare criteria for 24-hour supplemental oxygen due to severe hypoxemia at rest). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or Hospitalization, Whichever Occurs First | The primary outcome event is death or hospitalization, whichever occurs first. The difference between treatment groups on the primary outcome was assessed with a time-to-event analysis by calculation of the between group hazard ratio for the primary composite outcome; the statistical significance of the hazard ratio was determined from the log rank test. The uncertainty in the hazard ratio is expressed in the 95% confidence interval on the hazard ratio. | Through study completion. Median follow-up was 18.4 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | The difference between treatment groups in mortality is assessed with a time-to-event analysis by calculation of the between group hazard ratio for death; the statistical significance of the hazard ratio was determined from the log rank test. The uncertainty in the hazard ratio is expressed in the 95% confidence interval on the hazard ratio. | Through study completion. Median follow-up was 41.5 months. | 
| Health Care Utilization | Health care utilization is measured by the rate of all hospitalizations. | Through study completion. Median follow-up was 18.4 months. | 
| Adherence | Adherence is measured by self-reported hours of home oxygen per day | Through study completion. Median follow-up was 18.4 months. | 
| COPD Exacerbation | Rate of all COPD exacerbations | Through study completion. Median follow-up was 11.4 months | 
| Preference-weighted Health-related Quality of Life | Preference-weighted health-related quality of life is measured by change in the Quality of Well-being Scale total daily score, follow-up value minus baseline value. The total daily score ranges from 0 to 1 with higher score indicating more better quality of life. Death is scored 0. Greater change, follow-up minus baseline, indicates improvement in quality of life compared to baseline. Change scores may range from -1 to +1. | Baseline to 1 year | 
| Disease-specific Quality of Life | Disease-specific quality of life is measured by the change in the St George's Respiratory Questionnaire total score, follow-up value minus baseline value. The total score ranges from 0 to 100 with lower score indicating fewer respiratory symptoms. Change in score, follow-up minus baseline may range from -100 to +100, with lower values indicating improvement in disease-specific quality of life. | Baseline to 1 year | 
| General Quality of Life | General quality of life is measured by the change in the physical component summary subscale of the SF-36 quality of life questionnaire, follow-up value minus baseline value. The physical component summary subscale score ranges from 0 to 100 with higher values indicating better physical functioning. The change in score, follow-up minus baseline value, ranges from -100 to +100 with higher values indicating improvement in physical functioning. | Baseline to 1 year | 
| Sleep Quality | Sleep quality is measured by the change in the Pittsburgh Sleep Quality Index total score, follow-up value minus baseline value. The Pittsburgh Sleep Quality Index total score ranges from 0 to 21 with higher values indicating worse sleep quality. The change in score, follow-up minus baseline value, ranges from -21 to +21 with higher values indicating worsening in sleep quality. | Baseline to 1 year | 
| Anxiety | Anxiety is measured by the change in the Hospital Anxiety and Depression Scale (HADS) anxiety score, follow-up value minus baseline value. The HADS anxiety score ranges from 0 to 21 with higher values indicating greater anxiety. The change in score, follow-up minus baseline value, ranges from -21 to +21 with higher values indicating increase in anxiety | Baseline to 1 year | 
| Depression | Depression is measured by the change in the Hospital Anxiety and Depression Scale (HADS) depression score, follow-up value minus baseline value. The HADS depression score ranges from 0 to 21 with higher values indicating greater depression. The change in score, follow-up minus baseline value, ranges from -21 to +21 with higher values indicating increase in depression | Baseline to 1 year | 
| Development of Severe Resting Desaturation | Severe resting desaturation is defined as resting room air SpO2 <=88% | Baseline to 1 year | 
| 6-minute Walk Distance | Change in distance walked during 6-minute walk test, follow-up value minus baseline value (feet) | Baseline to 1 year | 
| Dyspnea | Change in dyspnea is measured by change in the St George's Respiratory Questionnaire (SGRQ) total score, follow-up value minus baseline value. The SGRQ total score ranges from 0 to 100, with higher values indicating worse dyspnea. The change in score, follow-up value minus baseline value, ranges from -100 to +100, with higher values indicating increase in dyspnea. | Baseline to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD