ARrest RESpiraTory Failure From PNEUMONIA

NCT ID: NCT04193878

Last Updated: 2025-08-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 465 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2025-07-22

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Inhaled placebo

Intervention Type: DRUG

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

Intervention

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

Group Type: ACTIVE_COMPARATOR

Inhaled budesonide and formoterol

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Inhaled placebo

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

Intervention Type: DRUG

Other Intervention Names

Pulmicort Respules (budesonide) and Perforomist (formoterol); aerosolized 0.9% saline

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Joseph Levitt, MD

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph Levitt, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Emir Festic, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

University of Alabama Birmingham - Main & Highlands

Birmingham, Alabama, United States

Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States

University of Arizona - Main & South Campus

Tucson, Arizona, United States

Stanford University

Palo Alto, California, 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

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins University - Main Campus & Bayview

Baltimore, Maryland, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

New York University - Langone Health

New York, New York, United States

Temple University

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33493423 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32738928 (View on PubMed)

Other Identifiers

1UG3HL141722-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

53599

Identifier Type: -

Identifier Source: org_study_id