Long-term Oxygen Treatment Trial

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.

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