Clinical trial NCT00692198: Long-term Oxygen Treatment Trial
Official title: Effectiveness of Long-term Oxygen Therapy in Treating People With Chronic Obstructive Pulmonary Disease With Moderate Desaturation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
Collaborators: name: Centers for Medicare and Medicaid Services
First posted: 2008-06-06
Enrollment: 738
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Death or Hospitalization, Whichever Occurs First
timeFrame: Through study completion. Median follow-up was 18.4 months.
Secondary outcomes:
measure: Death
timeFrame: Through study completion. Median follow-up was 41.5 months.
measure: Health Care Utilization
timeFrame: Through study completion. Median follow-up was 18.4 months.
measure: Adherence
timeFrame: Through study completion. Median follow-up was 18.4 months.
measure: COPD Exacerbation
timeFrame: Through study completion. Median follow-up was 11.4 months
measure: Preference-weighted Health-related Quality of Life
timeFrame: Baseline to 1 year
measure: Disease-specific Quality of Life
timeFrame: Baseline to 1 year
measure: General Quality of Life
timeFrame: Baseline to 1 year
measure: Sleep Quality
timeFrame: Baseline to 1 year
measure: Anxiety
timeFrame: Baseline to 1 year
measure: Depression
timeFrame: Baseline to 1 year
measure: Development of Severe Resting Desaturation
timeFrame: Baseline to 1 year
measure: 6-minute Walk Distance
timeFrame: Baseline to 1 year
measure: Dyspnea
timeFrame: Baseline to 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Medical Center
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda VA Medical Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Gainseville
country: United States
facility: North Florida/South Georgia VA
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Weston
country: United States
facility: Weston Florida Cleveland Clinic
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Elk Grove Village
country: United States
facility: Suburban Lung Associates
state: Illinois
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: West Roxbury
country: United States
facility: Boston VA Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: St. Louis
country: United States
facility: Pulmonary Consultants Inc./Christian Hospital
state: Missouri
city: Buffalo
country: United States
facility: Buffalo VAMC
state: New York
city: Syracuse
country: United States
facility: Crouse Medical Practice
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Kaiser Foundation Hospitals
state: Oregon
city: Danville
country: United States
facility: Geisinger Institute
state: Pennsylvania
city: Langhorne
country: United States
facility: Institute for Respiratory and Sleep Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Wyomissing
country: United States
facility: Respiratory Specialists
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Seattle
country: United States
facility: Puget Sound VA Medical Center
state: Washington
Study officials:
affiliation: University of Alabama at Birmingham Lung Health Center
name: William C. Bailey, MD
role: STUDY_CHAIR
References:
citation: Long-Term Oxygen Treatment Trial Research Group; Albert RK, Au DH, Blackford AL, Casaburi R, Cooper JA Jr, Criner GJ, Diaz P, Fuhlbrigge AL, Gay SE, Kanner RE, MacIntyre N, Martinez FJ, Panos RJ, Piantadosi S, Sciurba F, Shade D, Stibolt T, Stoller JK, Wise R, Yusen RD, Tonascia J, Sternberg AL, Bailey W. A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-1627. doi: 10.1056/NEJMoa1604344.
citation: Moy ML, Harrington KF, Sternberg AL, Krishnan JA, Albert RK, Au DH, Casaburi R, Criner GJ, Diaz P, Kanner RE, Panos RJ, Stibolt T, Stoller JK, Tonascia J, Yusen RD, Tan AM, Fuhlbrigge AL; LOTT Research Group. Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial. Respir Med. 2019 Mar;149:52-58. doi: 10.1016/j.rmed.2019.02.004. Epub 2019 Feb 13.
citation: Yusen RD, Criner GJ, Sternberg AL, Au DH, Fuhlbrigge AL, Albert RK, Casaburi R, Stoller JK, Harrington KF, Cooper JAD Jr, Diaz P, Gay S, Kanner R, MacIntyre N, Martinez FJ, Piantadosi S, Sciurba F, Shade D, Stibolt T, Tonascia J, Wise R, Bailey WC; LOTT Research Group *; LOTT Research Group. The Long-Term Oxygen Treatment Trial for Chronic Obstructive Pulmonary Disease: Rationale, Design, and Lessons Learned. Ann Am Thorac Soc. 2018 Jan;15(1):89-101. doi: 10.1513/AnnalsATS.201705-374SD.
citation: Stoller JK, Aboussouan LS, Kanner RE, Wilson LA, Diaz P, Wise R; LOTT Research Group. Characteristics of Alpha-1 Antitrypsin-Deficient Individuals in the Long-term Oxygen Treatment Trial and Comparison with Other Subjects with Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2015 Dec;12(12):1796-804. doi: 10.1513/AnnalsATS.201506-389OC.