Project Details
Description
PROJECT SUMMARY/ABSTRACT:
AIMS: The enclosed proposal outlines a phase III multicenter randomized clinical trial to establish the efficacy
of early treatment with an inhaled corticosteroid combined with a beta-agonist vs. usual care for prevention of
acute respiratory failure from pneumonia. This trial builds closely upon our recently completed NHLBI-funded
Lung Injury Prevention Study with Budesonide and a Beta-agonist (LIPS-B) demonstrating that early treatment
with aerosolized budesonide (a corticosteroid) and formoterol (a beta-agonist) improved oxygenation and
reduced acute respiratory failure (ARF) in high-risk patients in the emergency department. The current trial will
enroll 600 patients across 10 academic centers in U.S. and be conducted within the Discovery Network of the
Society of Critical Care Medicine. Secondary aims will explore risk factors for respiratory failure and potential
heterogenous treatment effects (HTE) in clinically and biologically defined subgroups. SIGNIFICANCE:
Pneumonia is the leading infectious cause of hospitalization and death in the United States. Currently, other
than antibiotics and supportive care, no established treatments directly target the lung injury that occurs with
severe pneumonia. However, corticosteroids have been shown to reduce inflammation and preserve alveolar
barrier function, while beta-agonists increase resorption of pulmonary edema and preserve vascular
permeability—potentially crucial functions in preventing ARF in patients with pneumonia. Our recently
completed phase IIa clinic trial suggest benefit of inhaled corticosteroids combined a beta-agonist. A trial to
establish efficacy of these therapies, and to inform optimal treatment of patients hospitalized for pneumonia, is
both timely and of critical importance to the mission of the NHLBI. INNOVATION: This trial will continue the
critical innovation of early intervention to prevent disease progression in LIPS-B. Previous trials of beta-
agonists and systemic steroids failed to show clinic benefits in mechanically ventilated patients with
established ARDS. LIPS-B delivered aerosolized study drug within a median of 9 hours from presentation and
prior to ARF, and demonstrated improved oxygenation and lower rates of ARF. We suspect that both early
treatment and inhaled delivery are critical innovations responsible for these encouraging results. IMPACT: If
we establish efficacy of these safe, inexpensive, and widely available medications, we will dramatically impact
treatment of a major cause of hospitalization and death. Regardless of the trial’s results, our exploratory
secondary aim will inform design of future trials in a field of special interest to the NHLBI.
Status | Active |
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Effective start/end date | 9/1/20 → 8/31/24 |
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