ARrest RESpiraTory Failure From PNEUMONIA

NCT04193878 | Terminated Phase 3 DMC FDA Drug

• 2 other identifiers: 535991UG3HL141722-01A1
• Study Type: interventional
• Target: 465
• Locations: 1 country
• Sites: 12

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Acute respiratory failure (ARF)

  High flow nasal cannula (HFNC \>=20L/mon O2) 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 Outcomes (5)

• Hospital length of stay

  within 60 days of randomization

• Duration of need for supplemental oxygen

  within 30 days of randomization

• Proportion of patients intubated for respiratory failure

  Within 7 days of randomization

• Oxygen failure free days to day 28

  Until Day 28

• Progression to systemic steroid therapy for pneumonia

  during course of the study

Study Arms (2)

Placebo

PLACEBO COMPARATOR

4 ml aerosolized 0.9% saline every 12 hours x 10 doses

Drug: Inhaled placebo

Intervention

ACTIVE COMPARATOR

aerosolized formoterol (20 mcg/2 ml) and budesonide (1.0 mg/2 ml) every 12 hours x 10 doses

Drug: Inhaled budesonide and formoterol

Interventions

Inhaled budesonide and formoterol DRUG

aerosolized doses of budesonide (1.0 mg/2 ml) and formoterol (20 mg/2 ml) twice daily for up to 5 days

Also known as: Pulmicort Respules (budesonide) and Perforomist (formoterol)

Intervention

Inhaled placebo DRUG

aerosolized saline (4 ml of 0.9% saline) twice daily for up to 5 days

Also known as: aerosolized 0.9% saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years or older with
• Severe pneumonia defined as:
• \. 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:
• 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
• Known current immunosuppression preventing inflammatory response, OR
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (12)

University of Alabama Birmingham - Main & Highlands

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of Arizona - Main & South Campus

Tucson, Arizona, 85724, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Tulane University - Main & BUMC

New Orleans, Louisiana, 70112, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University - Main Campus & Bayview

Baltimore, Maryland, 21205, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

New York University - Langone Health

New York, New York, 10016, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Related Publications (2)

• 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.

  PMID: 33493423 DERIVED

• 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.

  PMID: 32738928 DERIVED

MeSH Terms

Conditions

Pneumonia; Hypoxia

Interventions

Formoterol Fumarate; Budesonide; Sodium Chloride

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Joseph Levitt, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Emir Festic, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 10, 2019
• Study Start: June 1, 2020
• Primary Completion: July 22, 2025
• Study Completion: July 22, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)