ARrest RESpiraTory Failure From PNEUMONIA


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Trial ID: NCT04193878


This research study seeks to establish the effectiveness of a combination of an inhaled corticosteroid and a beta agonist compared to placebo for the prevention of acute respiratory failure (ARF) in hospitalized patients with pneumonia and hypoxemia.

Official Title


Stanford Investigator(s)

Joseph Levitt, MD, MS
Joseph Levitt, MD, MS

Associate Professor of Medicine (Pulmonary and Critical Care Medicine)

Angela Rogers
Angela Rogers

Associate Professor of Medicine (Pulmonary and Critical Care)

Jennifer Wilson MD, MS

Clinical Associate Professor, Emergency Medicine


Inclusion Criteria:

Patients 18 years or older with

Severe pneumonia defined as:

1. Hospitalization for acute (defined as ≤ 14 days) onset of symptoms (cough, sputum
production, or dyspnea), AND 2. Radiographic evidence of pneumonia by chest radiograph or
CT scan, AND 3. One of the following:

   1. Evidence of systemic inflammation (temperature < 35◦C or > 38◦C OR WBC > or < upper or
   lower limits for site OR procalcitonin > 0.5 mcg/L), OR

   2. Known current immunosuppression preventing inflammatory response, OR

   3. High clinical suspicion of pneumonia with microbiologic confirmation of infection.
   Microbiologic confirmation will include a positive nasal swab for a known respiratory
   virus; a sputum culture growing a likely pathogenic organism plus moderate or greater
   WBCs (not required for immunocompromised patients); or a positive blood culture with a
   likely pathogenic organism - e.g., ¼ vials with S. Epidermidis would NOT qualify)

AND Hypoxemia defined as new requirement for daytime supplemental oxygen with SpO2 < 92% on
room air, ≤ 96% on ≥ 2 L/min oxygen, or > 6L/min or non-invasive ventilation regardless of
SpO2 at enrollment. Patients admitted with pneumonia but not meeting criteria for hypoxemia
will be followed for up to 24 hours from ED admission to enrolling hospital to assess for
development of qualifying hypoxemia.

Exclusion Criteria:

   - Inability to obtain consent within 24 hours of presentation to enrolling hospital (up
   to 12 hours allowed at transferring ED for maximum of 36 hours from presentation)

   - Intubation (or impending intubation) prior to enrollment

   a. Patients receiving HFNC oxygen or NIV prior to enrollment are not excluded

   - A condition requiring inhaled corticosteroids or beta-agonists (patients receiving
   inhaled beta-agonists in the ED without an established indication will be eligible if
   treating clinician is willing to discontinue subsequent treatments)

   - Chronic systemic steroid therapy equivalent to >10 mg prednisone

   - COVID-19 positive patients receiving > 6 mg dexamethasone (40 mg prednisone equivalent
   dose) except for stress dose steroids for septic shock

   - Non-COVID-19 pneumonia patients receiving systemic steroid > 10 mg prednisone except
   for stress dose steroids for septic shock

   - Chronic lung or neuromuscular disease requiring daytime oxygen or mechanical
   ventilation other than for obstructive sleep apnea (OSA) or obesity hypoventilation

   - Not anticipated to survive > 48 hours or not expected to require > 48 hours of

   - Contraindication or allergy to inhaled corticosteroids or beta-agonists

   - Patients with heart rate > 130 bpm, ventricular tachycardia or new supraventricular
   tachycardia within last 4 hours will be potentially eligible for enrollment after the
   condition has resolved

   - Patients with K+ < 3.0 will be potentially eligible for enrollment after the condition
   has resolved

   - Patient not committed to full support other than intubation or resuscitation (i.e.,
   DNR/DNI status allowed)

   - Pregnancy

   - Incarcerated individual

   - Physician refusal of consent to protocol

   - Patient/surrogate refusal of consent to protocol


drug: Inhaled budesonide and formoterol

drug: Inhaled placebo


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Joe Levitt, MD