High-dose inhaled nitric oxide for severe pneumonia caused by multidrug-resistant bacteria: a randomized controlled trial protocol.
This study protocol aims to evaluate the effects of high-dose inhaled nitric oxide in patients with severe pneumonia from multidrug-resistant bacteria, focusing on changes in Clinical Pulmonary Infection Score.
Where it sits
this study against the rest of the ll-37 corpusSummary and findings
This study protocol outlines a trial to evaluate the efficacy and safety of high-dose inhaled nitric oxide in patients with severe pneumonia caused by multidrug-resistant bacteria. Patients will receive either inhaled nitric oxide (200 ppm, twice daily for 30 min/session for 5 days) or sham inhalation. The primary outcome is the change in Clinical Pulmonary Infection Score from baseline to day 7.
Abstract
<h4>Introduction</h4>Severe pneumonia caused by multidrug-resistant (MDR) bacteria is associated with high mortality. Inhaled nitric oxide (NO) has antimicrobial activity, but clinical evidence in MDR severe pneumonia remains limited. This trial will evaluate the efficacy and safety of adjunctive high-dose inhaled NO in patients with severe pneumonia associated with MDR bacteria.<h4>Patients and methods</h4>This prospective, single-center, double-blind randomized controlled trial will be conducted at Jiangdu People's Hospital Affiliated with Yangzhou University from January 2026 to June 2027. Patients with suspected or confirmed severe pneumonia caused by MDR bacteria will be randomized 1:1 to standard treatment plus inhaled NO (200 ppm, twice daily for 30 min/session for 5 days) or standard treatment plus sham inhalation (0 ppm NO). The primary outcome is the change in Clinical Pulmonary Infection Score (CPIS) from baseline to day 7. Secondary outcomes include mortality, 28-day ventilator-free days, vasopressor-free days, antibiotic-free days, ICU-free days, and hospital-free days, CPIS and Sequential Organ Failure Assessment scores, microbiological eradication, citrullinated histone H3 and cell-free DNA concentrations, and ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO<sub>2</sub>/FiO<sub>2</sub>) ratios. Safety outcomes include methemoglobin and NO<sub>2</sub> thresholds, serum creatinine, airway hyperreactivity, and acute kidney injury. Primary and secondary outcomes will be analyzed in confirmed MDR participants; safety will be assessed in participants receiving at least one study-gas administration.<h4>Discussion</h4>This protocol tests a mechanistically plausible adjunctive therapy for MDR severe pneumonia. It will explore whether high-dose NO affects neutrophil extracellular trap activity.
Background
This study addresses the high mortality associated with severe pneumonia caused by multidrug-resistant bacteria, a significant clinical challenge. Inhaled nitric oxide has been suggested to have antimicrobial properties, but there is limited clinical evidence supporting its use in this specific context. This trial aims to fill the gap in knowledge regarding the efficacy and safety of this adjunctive therapy.
Methods
The study is designed as a prospective, single-center, double-blind randomized controlled trial with a planned enrollment of patients with suspected or confirmed severe pneumonia due to multidrug-resistant bacteria. Participants will be randomized to receive either standard treatment plus inhaled nitric oxide or standard treatment plus sham inhalation. The primary outcome measure is the change in Clinical Pulmonary Infection Score from baseline to day 7.
Results
Not reported in abstract.
Interpretation
The study protocol sets out a methodologically sound approach to evaluate the potential benefits of inhaled nitric oxide in a challenging patient population. However, without results, it is difficult to assess the clinical significance of the anticipated findings. The trial's design includes several secondary outcomes that may provide valuable insights into the therapy's effects, but confounding factors such as single-center design and the nature of the patient population may limit the generalizability of the results.
Key findings
- Primary outcome: change in Clinical Pulmonary Infection Score from baseline to day 7.
- Inhaled NO dosage: 200 ppm, twice daily for 30 min/session for 5 days.
- Study duration: January 2026 to June 2027.
- Randomization ratio: 1:1.
Limitations
- Not reported in abstract.
- Single-center trial may limit generalizability.
- No results available to assess efficacy or safety.