Acute Respiratory Failure, COVID-19 Pneumonia, Hypoxemia, Pneumonia
Conditions
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.
Interventions
DRUGInhaled 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
DRUGInhaled placebo
aerosolized saline (4 ml of 0.9% saline) twice daily for up to 5 days
Sponsors
Stanford University
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Respiratory Failure (ARF) | within 7 days of randomization (day 0) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | within 60 days of randomization (day 0) | — |
| Duration of Need for Supplemental Oxygen | within 30 days of randomization (day 0) | — |
| Proportion of Patients Intubated for Respiratory Failure | Within 7 days of randomization (day 0) | — |
| Oxygen Failure Free Days to Day 28 | Until Day 28 | — |
| Progression to Systemic Steroid Therapy for Pneumonia | Within 7 days of randomization (day 0) | Progression defined as initiating post-randomization, open-label steroids if not already receiving dexamethasone for COVID at baseline. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoseph Levitt, MD
Stanford University
PRINCIPAL_INVESTIGATOREmir Festic, MD
Mayo Clinic
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 67.0 years STANDARD_DEVIATION 17.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 391 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 52 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race/Ethnicity, Customized Other | 23 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized White | 330 Participants |
| Region of Enrollment United States | 230 Participants |
| Sex: Female, Male Female | 162 Participants |
| Sex: Female, Male Male | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 25 / 235 | 27 / 230 |
| other Total, other adverse events | 0 / 235 | 0 / 230 |
| serious Total, serious adverse events | 0 / 235 | 7 / 230 |
Outcome results
None listed