High-dose inhaled nitric oxide for adults with severe pneumonia on ventilators

High Dose Inhaled Nitric Oxide Therapy in Critically Ill Patients With Pneumonia: a Pilot, Double-blinded, Randomized, Controlled Trial

This study will test whether short courses of high-dose inhaled nitric oxide help adults on ventilators with severe pneumonia recover and how the treatment affects methemoglobin levels.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT06950294 on ClinicalTrials.gov

What this trial studies

This pilot is a double-blind, randomized, sham-controlled trial enrolling 34 mechanically ventilated adults with newly diagnosed community- or hospital-acquired pneumonia at Massachusetts General Hospital. Participants are randomized 1:1 to receive high-dose inhaled nitric oxide (starting at 250 ppm, not exceeding 300 ppm) for 40 minutes four times daily for five days or a sham intervention, alongside standard care. The study will closely monitor methemoglobin kinetics and safety during treatment and collect clinical efficacy outcomes. All participants are followed for 60 days to capture recovery and clinical course.

Who should consider this trial

Good fit: Adults aged 18 or older who are intubated and mechanically ventilated within 72 hours of a new diagnosis of community- or hospital-acquired pneumonia and who (or whose legally authorized representative) can provide informed consent are ideal candidates.

Not a fit: Patients with baseline methemoglobin ≥3%, certain genetic red blood cell disorders (e.g., G6PD deficiency, cytochrome b5 reductase deficiency, sickle cell), severe anemia, advanced renal failure, those already receiving inhaled NO, or those with DNR orders are excluded and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the therapy could shorten time to recovery from severe pneumonia and define a safe high-dose inhaled nitric oxide dosing approach for ventilated patients.

How similar studies have performed: Lower-dose inhaled nitric oxide has improved oxygenation in some critical care settings and small reports suggest possible antimicrobial effects, but high-dose regimens for pneumonia remain novel and not yet well established.

Eligibility criteria

Inclusion Criteria:

* 18 years or older
* Intubated and mechanically ventilated
* Within 72h of diagnosis of community- or hospital-acquired pneumonia
* Written informed consent obtained from patients or legally authorized representatives

Exclusion Criteria:

* Baseline methemoglobin 3% or higher
* Genetic diseases including glucose-6-phosphate dehydrogenase deficiency, cytochrome b5 reductase deficiency, sickle cell disease
* Oxygen saturation \< 88% on 100% inspired fraction of oxygen
* Anemia with hemoglobin \< 7.0 g/dl
* Acute cardiogenic shock requiring inotropic or mechanical support with an ejection fraction less than 20%
* eGFR \< 30 ml/min/1.73m2 or use of continuous renal replacement therapy
* Receiving inhaled NO therapy or decision to initiate inhaled NO therapy within 24 hours post randomization
* A decision to do-not-resuscitate (DNR)
* Enrollment in another experimental antimicrobial treatment protocol
* Patients for whom follow-up is expected to be impossible

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Lorenzo Berra, MD — Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital
• Study coordinator: Lorenzo Berra, MD

Conditions: Critical Illness, Pneumonia, High dose inhaled nitric oxide, Critical care, Methemoglobin