Clinical trial NCT04193878: ARrest RESpiraTory Failure From PNEUMONIA
Official title: ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pneumonia
Hypoxemia
Acute Respiratory Failure
COVID-19 Pneumonia
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Institutes of Health (NIH)
First posted: 2019-12-10
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 48 hours from ED admission to enrolling hospital to assess for development of qualifying hypoxemia.

Exclusion Criteria:

* Inability to randomize within 48 hours of presentation to enrolling hospital (randomization beyond 24 hours will be limited to patients with persistent hypoxemia defined by an SpO2 \< 97% while on \> 3L/min O2)
* 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 syndrome
* Not anticipated to survive \> 48 hours or not expected to require \> 48 hours of hospitalization
* 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

Primary outcomes:
measure: Acute respiratory failure (ARF)
timeFrame: within 7 days of randomization
Secondary outcomes:
measure: Hospital length of stay
timeFrame: within 60 days of randomization
measure: Duration of need for supplemental oxygen
timeFrame: within 30 days of randomization
measure: Proportion of patients intubated for respiratory failure
timeFrame: Within 7 days of randomization
measure: Oxygen failure free days to day 28
timeFrame: Until Day 28
measure: Progression to systemic steroid therapy for pneumonia
timeFrame: during course of the study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham - Main & Highlands
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Tucson
country: United States
facility: University of Arizona - Main & South Campus
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: New Orleans
country: United States
facility: Tulane University - Main & BUMC
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University - Main Campus & Bayview
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: New York University - Langone Health
state: New York
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
Study officials:
affiliation: Stanford University
name: Joseph Levitt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Emir Festic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levitt JE, Festic E, Desai M, Hedlin H, Mahaffey KW, Rogers AJ, Gajic O, Matthay MA; ARREST Pneumonia Clinical Trial Investigators. The ARREST Pneumonia Clinical Trial. Rationale and Design. Ann Am Thorac Soc. 2021 Apr;18(4):698-708. doi: 10.1513/AnnalsATS.202009-1115SD.
citation: Nicolau DV, Bafadhel M. Inhaled corticosteroids in virus pandemics: a treatment for COVID-19? Lancet Respir Med. 2020 Sep;8(9):846-847. doi: 10.1016/S2213-2600(20)30314-3. Epub 2020 Jul 30. No abstract available.