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ARrest RESpiraTory Failure From PNEUMONIA (ARREST)

Primary Purpose

Pneumonia, Hypoxemia, Acute Respiratory Failure

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Inhaled budesonide and formoterol
Inhaled placebo
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients 18 years or older with

  1. Severe Pneumonia defined as hospitalization for acute (defined as ≤ 14 days) onset of symptoms (cough, sputum production, or dyspnea) and radiographic evidence of pneumonia by chest radiograph or CT scan AND 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.

    AND

  2. 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:

  1. 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)
  2. Intubation (or impending intubation) prior to enrollment

    a. Patients receiving HFNC oxygen or NIV prior to enrollment are not excluded

  3. 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)
  4. Chronic systemic steroid therapy equivalent to >10 mg prednisone
  5. COVID-19 positive patients receiving > 6 mg dexamethasone (30 mg prednisone equivalent dose)
  6. Non-COVID-19 pneumonia patients receiving systemic steroid > 10 mg prednisone except for stress dose steroids for septic shock
  7. Chronic lung or neuromuscular disease requiring daytime oxygen or mechanical ventilation other than for obstructive sleep apnea (OSA) or obesity hypoventilation syndrome
  8. Not anticipated to survive > 48 hours or not expected to require > 48 hours of hospitalization
  9. Contraindication or allergy to inhaled corticosteroids or beta-agonists
  10. 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
  11. K+ < 3.0 will be potentially eligible for enrollment after the condition has resolved
  12. Patient not committed to full support other than intubation or resuscitation (i.e., DNR/DNI status allowed)
  13. Pregnancy
  14. Incarcerated individual
  15. Physician refusal of consent to protocol
  16. Patient/surrogate refusal of consent to protocol

Sites / Locations

  • University of Alabama-BirminghamRecruiting
  • Mayo Clinic - ScottsdaleRecruiting
  • University of Arizona - Main & South CampusRecruiting
  • Stanford UniversityRecruiting
  • University of Florida
  • Mayo Clinic - JacksonvilleRecruiting
  • Tulane University - Main & BUMCRecruiting
  • University of MarylandRecruiting
  • Johns Hopkins University - Main Campus & BayviewRecruiting
  • Mayo Clinic - RochesterRecruiting
  • New York University - Langone HealthRecruiting
  • Temple UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Intervention

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Hospital length of stay
Duration of need for supplemental oxygen
Proportion of patients intubated for respiratory failure
Oxygen failure free days to day 28
Progression to systemic steroid therapy for pneumonia

Full Information

First Posted
December 3, 2019
Last Updated
June 26, 2023
Sponsor
Stanford University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT04193878
Brief Title
ARrest RESpiraTory Failure From PNEUMONIA
Acronym
ARREST
Official Title
ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Hypoxemia, Acute Respiratory Failure, COVID-19 Pneumonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
600 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
4 ml aerosolized 0.9% saline every 12 hours x 10 doses
Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
aerosolized formoterol (20 mcg/2 ml) and budesonide (1.0 mg/2 ml) every 12 hours x 10 doses
Intervention Type
Drug
Intervention Name(s)
Inhaled budesonide and formoterol
Other Intervention Name(s)
Pulmicort Respules (budesonide) and Perforomist (formoterol)
Intervention Description
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
Intervention Name(s)
Inhaled placebo
Other Intervention Name(s)
aerosolized 0.9% saline
Intervention Description
aerosolized saline (4 ml of 0.9% saline) twice daily for up to 5 days
Primary Outcome Measure Information:
Title
Acute respiratory failure (ARF)
Description
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
Time Frame
within 7 days of randomization
Secondary Outcome Measure Information:
Title
Hospital length of stay
Time Frame
within 60 days of randomization
Title
Duration of need for supplemental oxygen
Time Frame
within 30 days of randomization
Title
Proportion of patients intubated for respiratory failure
Time Frame
Within 7 days of randomization
Title
Oxygen failure free days to day 28
Time Frame
Until Day 28
Title
Progression to systemic steroid therapy for pneumonia
Time Frame
during course of the study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joseph Levitt, MD
Phone
650-213-6683
Email
jlevitt@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Emir Festic, MD
Phone
9049827445
Email
Festic.Emir@mayo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Levitt, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emir Festic, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama-Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Carmelle Elie, MD
Email
melie@uabmc.edu
First Name & Middle Initial & Last Name & Degree
Marie-Carmelle Elie, MD
Facility Name
Mayo Clinic - Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rodrigo Cartin-Ceba, MD
Email
cartinceba.rodrigo@mayo.edu
First Name & Middle Initial & Last Name & Degree
Rodrigo Cartin-Ceba, MD
Facility Name
University of Arizona - Main & South Campus
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Bime, MD
Email
cbime@deptofmed.arizona.edu
First Name & Middle Initial & Last Name & Degree
Christian Bime, MD
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joe Levitt, MD
Phone
650-723-6381
Email
jlevitt@stanford.edu
First Name & Middle Initial & Last Name & Degree
Joe Levitt, MD
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Individual Site Status
Terminated
Facility Name
Mayo Clinic - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emir Festic, MD
Email
Festic.Emir@mayo.edu
First Name & Middle Initial & Last Name & Degree
Emir Festic, MD
Facility Name
Tulane University - Main & BUMC
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josh Denson, MD
Email
jdenson@tulane.edu
First Name & Middle Initial & Last Name & Degree
Josh Denson, MD
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kami Hu, MD
Email
khu@som.umaryland.edu
First Name & Middle Initial & Last Name & Degree
Kami Hu, MD
Facility Name
Johns Hopkins University - Main Campus & Bayview
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William Checkley, MD, PhD
Email
wcheckl1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
William Checkley, MD, PhD
Facility Name
Mayo Clinic - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ognjen Gajic, MD
Email
gajic.ognjen@mayo.edu
First Name & Middle Initial & Last Name & Degree
Ognjen Gajic, MD
Facility Name
New York University - Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Kaufman, MD
Email
David.A.Kaufman@nyumc.org
First Name & Middle Initial & Last Name & Degree
David Kaufman, MD
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nina Gentile, MD
Email
ngentile@temple.edu
First Name & Middle Initial & Last Name & Degree
Nina Gentile, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33493423
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.
Results Reference
derived
PubMed Identifier
32738928
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.
Results Reference
derived

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ARrest RESpiraTory Failure From PNEUMONIA

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