Prevention of altitude-related illness in patients with COPD by acetazolamide. RCT

Abstract

Introduction: The current randomized, placebo-controlled, double-blind trial evaluated whether acetazolamide (AZA) prevented altitude-related illness (ARI) in lowlanders with chronic obstructive pulmonary disease (COPD) ascending to high altitude.

Methods: 176 COPD patients, FEV₁ ≥40 to <80%predicted, living below 800m, were randomized to AZA (125-0-250mg/d) or placebo starting 24h before ascending to and while staying at 3100m for 48h. Primary outcome was the incidence of any of the following ARI at 3100m: acute mountain sickness (AMS, Lake Louise score >2 including headache), severe hypoxemia (SpO₂ <80%, >30min) or any discomfort requiring medical intervention. Arterial blood gases and other outcomes were also assessed. www.ClinicalTrials.gov NCT03156231.

Results: Of 90 patients (median age 58y, FEV₁ 64%predicted) randomized to placebo, 64 (71%) experienced ARI; of 86 patients (age 58y, FEV₁ 64%predicted) randomized to AZA, 35 (41%) experienced ARI, odds ratio 0.28, 95%CI 0.15 to 0.52, P<0.001. Compared to placebo, AZA reduced severe hypoxemia by 77% (incidence 48% vs. 12%, P<0.001) without changing AMS incidence (35% vs. 31%, P=0.579). At 3100m, day 2, AZA decreased PaCO₂ by -0.3kPa (-0.5 to -0.1) and increased PaO₂ by 0.8kPa (0.5 to 1.1) vs. placebo, P<0.001 both instances. No serious adverse events occurred.

Conclusions: In lowlanders with moderate to severe COPD, staying for 48h at 3100m, ARI were common. AZA reduced the incidence of ARI by 42% through prevention of severe hypoxemia while the occurrence of AMS remained unchanged. The results suggest that lowlanders with COPD going to high altitude may benefit from preventive treatment with AZA.

Grants: Swiss National Science Foundation, Lunge Zurich