Early CPAP in COVID-19 Patients With Respiratory Failure.

Eligible patients will be randomized to two treatment arms: current clinical practice
(control arm) and early treatment with CPAP in addition to current clinical practice
(experimental arm). To deal with the current emergency situation, the study will adopt an
adaptive design with a Bayesian continuous monitoring. Such design allows to stop the study
as soon as the data provide sufficient evidence of efficacy or ineffectiveness of the studied
treatment.

The primary endpoint of the study is the combination of intubation or death within 7 days of
randomization. The secondary endpoint is 30-day mortality.

All patients arriving at the ED will be evaluated to verify the presence of inclusion and
exclusion criteria. Randomization will be performed through an ad-hoc electronic case report
form (eCRF). Eligible patients should be randomized as soon as possible, possibly immediately
after the ED triage.

Patients randomized to the control arm will be treated according to current clinical
practice, which currently does not involve the use of CPAP. Therefore, these patients should
not start treatment with CPAP immediately after randomization. CPAP treatment, however, is
allowed at a later stage, if deemed appropriate according to clinical judgment.

Patients randomized to the experimental arm should begin treatment with CPAP as soon as
possible. CPAP should only be performed with a helmet, using a positive end-expiratory
pressure (PEEP) between 8 and 14 cmH2O and an inspired oxygen fraction (FiO2) between 40 and
60%. FiO2 and PEEP must be modulated, within the limits indicated above, so as to obtain a
saturation > 94%. Whenever this goal cannot be achieved, the patient should be referred to
the intensivist.