The aim of this multicenter, investigator-initiated, prospective, randomized, open-label,
non-inferiority study is to evaluate a prednisone prescribing strategy guided by eosinophil
blood count compared to the standard (systematic) administration of corticosteroids in
patients with COPD exacerbation requiring ventilatory support,.
Consecutive patients admitted to the ICU with hypercapnic respiratory failure consecutive to
COPD exacerbation, and requiring ventilatory support with non-invasive or invasive mechanical
ventilation, will be considered for inclusion in the study.
Patients fulfilling inclusion criteria and consenting to participate in the study, will be
randomized through a random table generated electronically, to eosinophil-guided group or to
control group.
In eosinophil-guided group, patients will receive prednisone at a dose of 1mg/kg/day for up
to 5 days or during the hospital stay if less than 5 days, only if the eosinophil count is>
2%,. Corticosteroid treatment is taken in the morning in patients with NIV, and through the
gastric tube in intubated patients.If blood eosinophil count is ≤2%, no corticosteroids are
given.
In the control group: A treatment based on prednisone at a daily dose of 1 mg/kg will be
routinely administered for a maximum of 5 days, or during the hospital stay, if it is less
than 5 days. Corticosteroid treatment is taken in the morning in patients with NIV, and
through the gastric tube in intubated patients.
The associated medications will be administered in a standardized way The hypothesis tested
is a non-inferiority of the "eosinophil-guided strategy" compared to the standard strategy,
with less exposure to corticosteroids.
The primary endpoint is the proportion of unventilated patients at day 6 in study-groups
which is set to 50% in the control group. A pre-specified difference <10% would be a
non-inferiority margin.
Secondary endpoints are: Number of ICU days alive without ventilatory support within 28 days
after recruitment, length of stay in intensive care Unit, the intubation rate in patients
initially under NIV, Mortality in the ICU, Hospital mortality.
Safety:New onset of diabetes or worsening of diabetes requiring the start or the increase in
insulin therapy, Upper gastrointestinal bleeding (2 g drop of Hb requiring blood transfusion
or fibroscopy), Uncontrolled hypertensive crisis requiring the introduction of new
antihypertensives, ICU-acquired neuromyopathy, Nosocomial infection, Relapse rate /
recurrence defined respectively by the rate of a new hospital consultation and/or admission
in the week or the month following index hospitalization.
Sample size calculation: In a non-inferiority study, with an incidence of the event (no
ventilation at D6) of 50% in the standard group and this same incidence less than 60% (10% of
acceptable difference for non-inferiority) , a power of 80% and alpha error <0.05, it would
take 86 patients per arm by anticipating 2% of lost sight
(http://www.pharmaschool.co/size8.asp).