Effectiveness of Long-term Oxygen Therapy in Treating People With Chronic Obstructive Pulmonary Disease (The Long-term Oxygen Treatment Trial [LOTT]) - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Collaborator:	Centers for Medicare and Medicaid Services
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00692198

Purpose

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.

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease	Behavioral: Supplemental oxygen therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Long-term Oxygen Treatment Trial

Resource links provided by NLM:

MedlinePlus related topics: Breathing Problems COPD (Chronic Obstructive Pulmonary Disease) Exercise and Physical Fitness Oxygen Therapy

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Death or hospitalization [ Time Frame: Measured every 4 months for up to 4.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease-specific quality of life [ Time Frame: Measured twice in year 1, twice in year 2, once in year 3, and once in year 4 ] [ Designated as safety issue: No ]
Preference-weighted health-related quality of life [ Time Frame: Measured twice in year 1, twice in year 2, once in year 3, and once in year 4 ] [ Designated as safety issue: No ]
Quality-adjusted survival [ Time Frame: Measured every 4 months for up to 4.5 years ] [ Designated as safety issue: No ]
Health care utilization [ Time Frame: Measured every 4 months for up to 4.5 years ] [ Designated as safety issue: No ]
Maintenance of nutritional status (e.g., body mass index) [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
General quality of life [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
Sleep quality [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
Depression and anxiety [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
Onset of severe hypoxemia (defined as room air oxygen saturation less than or equal to 88%) [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
6-minute walk distance [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
Dyspnea [ Time Frame: Measured once per year for up to 4.5 years ] [ Designated as safety issue: No ]
COPD exacerbation rate [ Time Frame: Measured every 4 months for up to 4.5 years ] [ Designated as safety issue: No ]
Adherence to supplemental oxygen [ Time Frame: Measured every 2 months for up to 4.5 years ] [ Designated as safety issue: No ]
Risk of cardiovascular disease [ Time Frame: Measured every 4 months for up to 4.5 years ] [ Designated as safety issue: No ]
Cost effectiveness [ Time Frame: Assessed at end of trial using quality adjusted survival ] [ Designated as safety issue: No ]

Estimated Enrollment:	1134
Study Start Date:	January 2009
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive treatment with supplemental oxygen therapy.	Behavioral: 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.
2: No Intervention 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).

Arms

Assigned Interventions

1: Experimental

Participants will receive treatment with supplemental oxygen therapy.

Behavioral: 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.

2: No Intervention

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).

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 4.5 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, a blood draw, and an at-home measurement of blood oxygen level over a 24-hour period. 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 4 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

Ages Eligible for Study:	40 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
Predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) percent less than or equal to 65% predicted
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00692198

Contacts

Contact: Alice Sternberg, ScM

410-955-3752

asternbe@jhsph.edu

Locations

United States, Alabama
University of Alabama	Recruiting
Birmingham, Alabama, United States, 35294
Contact: Debbie Brewton, RN 205-934-5555 dbrewton@uab.edu
Contact: Allen Cooper, MD 205-934-1339 allenc@uab.edu
Principal Investigator: Allen Cooper, MD
Sub-Investigator: Kathleen Harrington, PhD
Sub-Investigator: Mark Dransfield, MD
Birmingham VA Medical Center	Recruiting
Birmingham, Alabama, United States, 35233
Contact: Janet Bowden 205-933-8101 ext 5550 janet.bowden@va.gov
Contact: Allen Cooper, MD 205-934-1339 allenc@uab.edu
Principal Investigator: Allen Cooper, MD
United States, California
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Recruiting
Los Angeles, California, United States, 90502
Contact: Peggy Walker 310-222-8200 pwalker@labiomed.org
Contact: Richard Casaburi, MD, PhD 310-222-8200 casaburi@ucla.edu
Principal Investigator: Richard Casaburi, MD, PhD
Sub-Investigator: Janos Porszasz, MD
Loma Linda VA Medical Center	Recruiting
Loma Linda, California, United States, 92357
Contact: Kathleen Ellstrom 909-583-6095 kathleen.ellstrom@va.gov
Contact: Lennard Specht, MD 909-583-6098 norman.specht@va.gov
Principal Investigator: Richard Casaburi, MD, PhD
United States, Colorado
Denver Health and Hospital Authority	Recruiting
Denver, Colorado, United States, 80204
Contact: Christine Verano, RN, BSN 720-848-0757 chris.verano@uchsc.edu
Contact: Richard Albert, MD 303-436-6900 rick.albert@dhha.org
Principal Investigator: Richard Albert, MD
Sub-Investigator: Barry Make, MD
National Jewish Medical and Research Center	Recruiting
Denver, Colorado, United States, 80206
Contact: Jennifer Underwood 303-398-1518 underwoodj@njhealth.org
Contact: Barry Make, MD 303-398-1703 makeb@njhealth.org
Principal Investigator: Richard Albert, MD
University of Colorado	Recruiting
Aurora, Colorado, United States, 80045
Contact: Christine Verano 720-848-0757 chris.verano@ucdenver.edu
Contact: Marvin Schwartz 303-724-4075 marvin.schwartz@ucdenver.edu
Principal Investigator: Richard Albert, MD
United States, Kentucky
University of Kentucky	Recruiting
Lexington, Kentucky, United States, 40536
Contact: Rey Cortes 859-323-6176 rccort2@email.uky.edu
Contact: Dennis Doherty, MD 859-323-5944 dedohe0@email.uky.edu
Principal Investigator: Philip Diaz, MD
United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Susan Peterson, RRT 617-732-6272 speterson2@partners.org
Contact: Anne Fuhlbrigge, MD 617-525-2728 anne.fuhlbrigge@channing.harvard.edu
Principal Investigator: Anne Fuhlbrigge, MD, MS
Sub-Investigator: George Washko, MD
United States, Michigan
University of Michigan	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Catherine Meldrum, RN, BSN 734-647-7840 cathymel@umich.edu
Contact: Fernando Martinez, MD 734-763-2540 fmartine@umich.edu
Principal Investigator: Fernando Martinez, MD
Sub-Investigator: Jeffrey Curtis, MD
United States, Missouri
Washington University	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Jeanne Heaghney, RN 314-747-1610 jheaghne@dom.wustl.edu
Contact: Roger Yusen, MD 314-454-8764 ryusen@dom.wustl.edu
Principal Investigator: Roger Yusen, MD, MPH
Sub-Investigator: Mario Castro, MD, MPH
United States, North Carolina
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: Stephanie Keeting 919-613-6306 stephanie.keeting@duke.edu
Contact: Neil MacIntyre, MD 919-681-2720 macin001@mc.duke.edu
Principal Investigator: Neil MacIntyre, MD
Sub-Investigator: Michael Cicale, MD
Sub-Investigator: Yuh-Chin Tony Huang, MD, MHS
United States, Ohio
Cleveland Clinic Foundation	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Yvonne Meli 216-445-4215 meliy@ccf.org
Contact: James Stoller, MD 215-444-1960 stollej@ccf.org
Principal Investigator: James Stoller, MD, MS
Sub-Investigator: Kingman Strohl, MD
Sub-Investigator: Jeffrey Kern, MD
Ohio State University	Recruiting
Columbus, Ohio, United States, 43210
Contact: Janice Drake 614-366-2287 janice.drake@osumc.edu
Contact: Philip Diaz, MD 614-293-4925 philip.diaz@osumc.edu
Principal Investigator: Philip Diaz, MD
Sub-Investigator: Dennis Doherty, MD
Sub-Investigator: Ralph Panos, MD
Cincinnati VA Medical Center	Recruiting
Cincinnati, Ohio, United States, 45220
Contact: Laura Lach 513-861-3100 ext 4557 laura.lach@va.gov
Contact: Ralph Panos, MD 513-861-3100 ext 4500 panosrj@ucmail.uc.edu
Principal Investigator: Philip Diaz, MD
University Hospitals Case Medical Center	Recruiting
Cleveland, Ohio, United States, 44106
Contact: David Haney 216-844-2381 david.haney@uhhospitals.org
Contact: Jeffrey Kern, MD 216-844-8101 jeffrey.kern@uhhs.com
Principal Investigator: James Stoller, MD
United States, Oregon
Kaiser Foundation Hospitals	Recruiting
Portland, Oregon, United States, 97232
Contact: Nancy Siegel, MPH 503-335-6793 nancy.a.siegel@kpchr.org
Contact: Thomas Stibolt, MD 503-813-3638 tom.stibolt@kp.org
Principal Investigator: Thomas Stibolt, MD
Sub-Investigator: Richard Mularski, MD
Sub-Investigator: Allison Naleway, MD
United States, Pennsylvania
Temple University	Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Carla Grabianowski, RN, BSN 215-707-1359 carla.grabianowski@tuhs.temple.edu
Contact: Gerard Criner, MD 215-707-8113 gerard.criner@tuhs.temple.edu
Principal Investigator: Gerard Criner, MD
Sub-Investigator: Steven Scharf, MD, PhD
University of Pittsburgh	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Donna Smith, RRT, MS 412-647-9503 smithdd@upmc.edu
Contact: Frank Sciurba, MD 412-648-6492 sciurbafc@upmc.edu
Principal Investigator: Frank Sciurba, MD
Sub-Investigator: Charles Atwood, MD
United States, Utah
University of Utah	Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Martin Villegas 801-581-5864 martin.villegas@hsc.utah.edu
Contact: Richard Kanner, MD 801-581-7806 richard.kanner@hsc.utah.edu
Principal Investigator: Richard Kanner, MD
Sub-Investigator: Mary Beth Scholand, MD
United States, Washington
University of Washington	Recruiting
Seattle, Washington, United States, 98101
Contact: Edmunds Udris 206-764-2504 ed.udris@va.gov
Contact: David Au, MD, MS 206-277-6132 dau@u.washington.edu
Principal Investigator: David Au, MD, MS
Sub-Investigator: Bruce Culver, MD
Puget Sound VA Medical Center	Recruiting
Seattle, Washington, United States, 98108
Contact: Edmunds Udris 206-764-2504 ed.udris@va.gov
Contact: David Au, MD 206-277-6132 dau@u.washington.edu
Principal Investigator: David Au, MD
Harborview Medical Center	Recruiting
Seattle, Washington, United States, 98101
Contact: Edmunds Udris 206-764-2504 ed.udris@va.gov
Contact: Randall Curtis, MD, MPH 206-744-3356 jrc@u.washington.edu
Principal Investigator: David Au, MD, MS

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Centers for Medicare and Medicaid Services

Investigators

Study Chair:

William C. Bailey, MD

University of Alabama at Birmingham Lung Health Center

Responsible Party:	NHLBI ( Antonello Punturieri, MD, PhD )
Study ID Numbers:	583, N01 HR76197
Study First Received:	June 4, 2008
Last Updated:	November 20, 2009
ClinicalTrials.gov Identifier:	NCT00692198 History of Changes
Health Authority:	United States: Federal Government