Nasal high-flow compared to non-invasive ventilation in treatment of acute acidotic hypercapnic exacerbation of chronic obstructive pulmonary disease-protocol for a randomized controlled noninferiority trial (ELVIS).

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a major negative impact on health status, rates of hospitalization, readmission, disease progression and mortality. Non-invasive ventilation (NIV) is the standard therapy for hypercapnic acidotic respiratory failure in AECOPD. Despite its beneficial effects, NIV is often poorly tolerated (11-34 % failure rate). An increasing number of studies have documented a beneficial effect of nasal high-flow (NHF) in acute hypercapnia. We designed a prospective, randomized, multi-centre, open label, non-inferiority trial to compare treatment failure in nasal NHF vs NIV in patients with acidotic hypercapnic AECOPD.

METHODS: The study will be conducted in about 35 sites in Germany. Patients with hypercapnic AECOPD with respiratory acidosis (pH < 7.35) will be randomized 1:1 to NIV or NHF. The primary outcome is the combined endpoint of intubation, treatment failure or death at 72 h. The switch from one to the other device marks a device failure but acts as a rescue treatment in absence of intubation criteria. A sample size of 720 was calculated to have 80% power for showing that NHF is non-inferior to NIV with a margin of 8 percentage points. Linear regression will be used for the confirmatory analysis.

DISCUSSION: If NHF is shown to be non-inferior to NIV in acidotic hypercapnic AECOPD, it could become an important alternative treatment.

TRIAL REGISTRATION: ClinicalTrials.gov , NCT04881409 , Registered on May 11, 2021.