A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation

Abstract

Background: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation.

Methods: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked.

Results: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes.

Conclusions: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .).

Figures

Figure 1. Kaplan–Meier Analyses of the Primary Outcome of Death or First Hospitalization for Any Cause and for the Component Events in the Intention-to-Treat Population

Panel A shows the results of a time-to-event analysis of the primary outcome, which was a composite of death or first hospitalization for any cause; the median follow-up was 18.4 months. Data for 120 patients who were assigned to receive long-term supplemental oxygen (supplemental-oxygen group) and 120 assigned to receive no long-term supplemental oxygen (no-supplemental-oxygen group) who neither died nor had a hospitalization were censored at the date of the last interview. Error bars indicate 95% confidence intervals (assessed every 12 months). For the time-to-event analysis of the first hospitalization for any cause, the median follow-up was 18.4 months. Data for 139 patients in the supplemental-oxygen group and 133 in the no-supplemental-oxygen group were censored as of their date of death (if there was no hospitalization before death) or as of the date of their last interview (if they were alive and had no hospitalization). Panel B shows the results of a time-to-event analysis of death; the median follow-up was 41.5 months. Data for 302 patients in the supplemental-oxygen group and 297 in the no-supplemental-oxygen group who were alive on August 31, 2015, were censored as of that date. The hazard ratios and 95% confidence limits were derived from Cox regression models, with supplemental oxygen versus no supplemental oxygen as the single model variable. P values were derived from log-rank tests. For the components of the composite primary outcome (death and first hospitalization), a P value of less than 0.025 (0.05 divided by 2) was considered to indicate statistical significance, with the use of a Bonferroni adjustment for multiple comparisons.

Figure 2. Self-Reported Use of Supplemental Oxygen during Follow-up

Shown are histograms of total self-reported hours of supplemental-oxygen use per day (sum of stationary use and portable use) according to randomized assignment and prescription for supplemental oxygen (24-hour use or use during sleep and exercise). Plus–minus values are means ±SD. The value plotted for a patient is the mean of all the patient’s self-reports during follow-up. Self-reports were obtained 3 times yearly in the no-supplemental-oxygen group. In the supplemental-oxygen group, self-reports were more frequent during year 1 (12 times) and were obtained 3 times yearly thereafter. The median number of self-reports for a patient was 20 in the supplemental-oxygen group (range, 6 to 20) and 8 in the no-supplemental-oxygen group (range, 0 to 18). All the patients in the supplemental-oxygen group provided at least one assessment; 363 patients (98%) in the no-supplemental-oxygen group provided at least one assessment. IQR denotes interquartile range.