ARrest RESpiraTory Failure From PNEUMONIA

Pneumonia Clinical Trial

— ARREST  

Official title:

ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04193878
• Other study ID #: 53599
• Secondary ID: 1UG3HL141722-01A
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2020
• Est. completion date: August 31, 2025

Study information

• Verified date: June 2023
• Source: Stanford University
• Contact: Joseph Levitt, MD
• Phone: 650-213-6683
• Email: jlevitt[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: August 31, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Acute Respiratory Failure
• COVID-19 Pneumonia
• Hypoxemia
• Hypoxia
• Pneumonia
• Respiratory Insufficiency

Intervention

Drug:
• Inhaled budesonide and formoterol
aerosolized doses of budesonide (1.0 mg/2 ml) and formoterol (20 mg/2 ml) twice daily for up to 5 days
• Inhaled placebo
aerosolized saline (4 ml of 0.9% saline) twice daily for up to 5 days

Locations

Country	Name	City	State
United States	Johns Hopkins University - Main Campus & Bayview	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama-Birmingham	Birmingham	Alabama
United States	University of Florida	Gainesville	Florida
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Tulane University - Main & BUMC	New Orleans	Louisiana
United States	New York University - Langone Health	New York	New York
United States	Stanford University	Palo Alto	California
United States	Temple University	Philadelphia	Pennsylvania
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	University of Arizona - Main & South Campus	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute respiratory failure (ARF)	High flow nasal cannula (HFNC) and/or Noninvasive ventilation (NIV) use for greater than 36 hours OR Invasive mechanical ventilation for greater than 36 hours OR Death in a patient placed on respiratory support (HFNC, NIV, ventilator) who dies before 36 hours	within 7 days of randomization
Secondary	Hospital length of stay		within 60 days of randomization
Secondary	Duration of need for supplemental oxygen		within 30 days of randomization
Secondary	Proportion of patients intubated for respiratory failure		Within 7 days of randomization
Secondary	Oxygen failure free days to day 28		Until Day 28
Secondary	Progression to systemic steroid therapy for pneumonia		during course of the study