Burdensome Therapy for Severe Hypoxemia in COPD Patients Is Overkill, Trial Says

The decades-long practice of prescribing long-term oxygen for 24 hours a day to patients with severe hypoxemia from chronic lung diseases appears unnecessary, according to findings from a randomized trial.

In patients assigned to 24 hours of oxygen a day, the risk for hospitalization or death was no different at 12 months compared with those randomized to 15 hours a day (64.1% vs 63.7%, respectively; HR 0.99, 95% CI 0.72-1.36, P=0.007 for non-superiority), reported Magnus Ekström, MD, PhD, of Blekinge Hospital in Karlskrona, Sweden, at the annual European Respiratory Society (ERS) congress in Vienna.

Maximal oxygen therapy was not superior for either component of the primary outcome as well: death from any cause (31.6% vs 27.4%, respectively), hospitalization for any cause (57.3% in both groups). Furthermore, patient-reported outcomes — including breathlessness, fatigue, health status, and physical activity — were no different between groups after a year.

Findings from the so-called REDOX trial were published simultaneously in the New England Journal of Medicine (NEJM).

Every year in the U.S., more than a million patients are prescribed long-term oxygen therapy based on findings from two randomized studies from the 1970s showing the practice substantially prolonged survival in chronic obstructive pulmonary disease (COPD) patients with severe hypoxemia. The U.S. Nocturnal Oxygen Therapy Trial used 24 hours of therapy (vs nighttime use alone), while the U.K. Medical Research Council trial examined 15 hours of daily use (vs no supplemental oxygen).

A non-randomized comparison of those two studies suggesting a trend toward better survival with greater oxygen use led to guidelines recommending at least 15 hours of therapy, with 24 hours considered optimal. “That can be very burdensome for our patients,” said Ekström.

In the new study, patients in the 15-hour group used oxygen during the night and could go without it for 9 hours during the day.

“This actually gives reassurance to patients, caregivers, and clinicians that it seems safe for patients to be off the treatment,” said Ekström. “It can give flexibility to their lives and might decrease the burden of the therapy.”

Despite the proven survival advantage, it remains difficult to convince patients to use long-term oxygen therapy for multiple reasons, according to Darren Taichman, MD, PhD, the deputy editor and online editor at NEJM, and Jeffrey Drazen, MD, the former NEJM editor-in-chief, writing in an editorial accompanying the publication.

Most systems for oxygen therapy are heavy, cumbersome, and potentially dangerous, as already frail patients can fall over the tubing, the editorialists noted, and patients also worry about looking “like a ‘sick person.'”

As well, “many patients do not feel better while using supplemental oxygen, and as a consequence, long-term oxygen therapy contributes to substantial social isolation and depression, to the extent that many patients choose to endure hypoxemia rather than use oxygen therapy as recommended,” wrote Taichman and Drazen.

During the ERS session where the data were presented, Taichman said that prescribing oxygen and convincing patients to use it has been one of the most difficult things he’s had to do in his decades of practice.

“We’re essentially tying them up to a ball and chain for the rest of their lives,” said Taichman, a pulmonologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, adding that many patients, if they want to get anywhere, need somebody else to help “lug the equipment around.”

More portable systems exist, but they have limitations on flow rates and duration of use, not to mention reimbursement hurdles, he said.

For clinicians and patients alike, these new data should give a lot of reassurance that it’s OK for patients to go to a party or a movie or to spend time with family without the equipment for a couple of hours a day, said Taichman. “So they still have that ball and chain, but maybe we’ve lightened it a little bit.”

From 2018 to 2022, the phase IV REDOX (Registry-Based Treatment Duration and Mortality in Long-Term Oxygen Therapy) trial randomized 241 patients with severe hypoxemia to long-term oxygen therapy for either 24 hours or 15 hours per day.

Patients in the study had a mean age of 76 years, and 59% were women. COPD (71%) and pulmonary fibrosis (14%) were the most common causes of severe hypoxemia. Patients had a “really severe level of hypoxemia,” noted Ekström, with a mean partial pressure of arterial oxygen of 48.8 mm Hg (6.5 kPa) when breathing air.

In subgroup analyses of the primary endpoint of death or hospitalization at 1 year, no benefit was seen for the 24-hour group versus the 15-hour group:

• Per-protocol population: 72% vs 58%, respectively (HR 1.27, 95% CI 0.85-1.90)
• Severe hypoxemia subgroup: 67% vs 64% (HR 1.09, 95% CI 0.77-1.53)
• COPD subgroup: 68% vs 61% (HR 1.11, 95% CI 0.71-1.73)
• Non-COPD subgroup: 65% vs 69% (HR 1.06, 95% CI 0.59-1.89)

Overall, the majority of patients (58%) in the study said they would prefer the 15-hour therapy.

Due to funding constraints, daily oxygen use was self-reported. At 3 months, median daily use was 23 hours in the 24-hour group and 15 hours in the 15-hour group, reaching a median 24 hours (interquartile range [IQR] 21-24) and 15 hours (IQR 15-16), respectively, at 12 months.