Long-term Oxygen Treatment Trial

NCT ID: NCT00692198

Last Updated: 2017-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 738 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2015-08-31

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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Supplemental oxygen therapy

Participants will receive treatment with supplemental oxygen therapy.

Group Type: EXPERIMENTAL

Supplemental oxygen therapy

Intervention Type: DRUG

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.

No supplemental oxygen therapy

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Supplemental oxygen therapy

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.

Intervention Type: DRUG

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

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

Sponsors

Centers for Medicare and Medicaid Services

FED

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William C. Bailey, MD

Role: STUDY_CHAIR

University of Alabama at Birmingham Lung Health Center

Locations

Birmingham VA Medical Center

Birmingham, Alabama, United States

University of Alabama

Birmingham, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

Loma Linda VA Medical Center

Loma Linda, California, United States

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Los Angeles, California, United States

UCSD Medical Center

San Diego, California, United States

Denver Health and Hospital Authority

Denver, Colorado, United States

National Jewish Medical and Research Center

Denver, Colorado, United States

North Florida/South Georgia VA

Gainseville, Florida, United States

Central Florida Pulmonary Group

Orlando, Florida, United States

Weston Florida Cleveland Clinic

Weston, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Suburban Lung Associates

Elk Grove Village, Illinois, United States

Louisiana State University Health Sciences Center

New Orleans, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Boston VA Medical Center

West Roxbury, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Beaumont Hospital

Royal Oak, Michigan, United States

Washington University

St Louis, Missouri, United States

Pulmonary Consultants Inc./Christian Hospital

St Louis, Missouri, United States

Buffalo VAMC

Buffalo, New York, United States

Crouse Medical Practice

Syracuse, New York, United States

Duke University

Durham, North Carolina, United States

Cincinnati VA Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Kaiser Foundation Hospitals

Portland, Oregon, United States

Geisinger Institute

Danville, Pennsylvania, United States

Institute for Respiratory and Sleep Medicine

Langhorne, Pennsylvania, United States

Temple University

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Respiratory Specialists

Wyomissing, Pennsylvania, United States

University of Texas at San Antonio

San Antonio, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Harborview Medical Center

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Puget Sound VA Medical Center

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 27783918 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30803886 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29087741 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26653189 (View on PubMed)

Related Links

https://jhuccs1.us/lott/

Click here for more information about the Long-term Oxygen Treatment Trial

Other Identifiers

N01HR76197-12-0-3

Identifier Type: NIH

Identifier Source: secondary_id

View Link

583

Identifier Type: -

Identifier Source: org_study_id