Preventing respiratory failure in pneumonia patients

ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA)

This study is testing if a mix of inhaled medications can help hospitalized adults with pneumonia and low oxygen levels avoid serious breathing problems.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 600 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Stanford University (Academic / other)
• Drugs / interventions: prednisone
• Locations: 12 sites (Birmingham, Alabama and 11 other locations)
• Trial ID: NCT04193878 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a combination of inhaled corticosteroid and beta agonist in preventing acute respiratory failure in hospitalized patients suffering from pneumonia and hypoxemia. Participants will receive either the active treatment or a placebo to determine the intervention's impact on their respiratory outcomes. The study aims to enroll adults aged 18 and older who meet specific criteria related to pneumonia severity and hypoxemia. The trial is designed to provide insights into potential new treatment options for this critical condition.

Who should consider this trial

Good fit: Ideal candidates for this study are hospitalized adults aged 18 and older with severe pneumonia and hypoxemia.

Not a fit: Patients with mild pneumonia or those not requiring hospitalization may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the incidence of acute respiratory failure in patients with pneumonia.

How similar studies have performed: Other studies have explored similar interventions for respiratory conditions, showing promising results, but this specific combination is being tested for the first time in this context.

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

Where this trial is running

Birmingham, Alabama and 11 other locations

• University of Alabama Birmingham - Main & Highlands — Birmingham, Alabama, United States (Recruiting)
• Mayo Clinic - Scottsdale — Scottsdale, Arizona, United States (Recruiting)
• University of Arizona - Main & South Campus — Tucson, Arizona, United States (Recruiting)
• Stanford University — Palo Alto, California, United States (Recruiting)
• University of Florida — Gainesville, Florida, United States (Terminated)
• Mayo Clinic - Jacksonville — Jacksonville, Florida, United States (Recruiting)
• Tulane University - Main & BUMC — New Orleans, Louisiana, United States (Recruiting)
• University of Maryland — Baltimore, Maryland, United States (Recruiting)
• Johns Hopkins University - Main Campus & Bayview — Baltimore, Maryland, United States (Recruiting)
• Mayo Clinic - Rochester — Rochester, Minnesota, United States (Recruiting)
• New York University - Langone Health — New York, New York, United States (Recruiting)
• Temple University — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Joseph Levitt, MD — Stanford University
• Study coordinator: Joseph Levitt, MD

Conditions Pneumonia; Hypoxemia; Acute Respiratory Failure; COVID-19 Pneumonia