An Early Phase 1 interventional study of High dose inhaled nitric oxide and Sham treatment in Critical Illness and Pneumonia, sponsored by Massachusetts General Hospital. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-22.
Sponsored by Massachusetts General Hospital · Early Phase 1, Interventional, and Treatment
The goal of this clinical trial is to learn the formation and recovery rate of methemoglobin (MetHb) in severely sick patients with pneumonia who receive high doses of inhaled nitric oxide (iNO) therapy at 250 parts per million (ppm), not exceeding 300 ppm. Meanwhile, the benefits of the therapy to treat severely sick patients with pneumonia will be explored. Patients who are 18 years or older, newly diagnosed with pneumonia, and severely sick with requirement of a breathing machine could be included. The main questions it aims to answer are:
How does methemoglobin change through the iNO treatment? Does iNO therapy increase the number of patients recovering from pneumonia? Researchers will compare iNO treatment to placebo, which means using the same device as the treatment group without delivering the study drug.
Participants will:
This study is designed as a pilot, double-blinded, randomized controlled trial to investigate levels of methemoglobin in the treatment group versus the control group and efficacy of high dose inhaled NO among critically ill patients with pneumonia. We will enroll 34 adult patients with newly diagnosed pneumonia and invasive mechanical ventilation who are admitted to the ICUs at Massachusetts General Hospital.
After enrollment, participants will be randomized in 1:1 ratio to intervention group or control group. Baseline characteristics will be collected.
During treatment period, patients allocated to the intervention group will receive high dose inhaled NO starting at 250 ppm (not exceeding 300 ppm), 40min, 4 times daily, for 5 days. The control group will receive sham intervention. Both groups will receive standard therapy.
During follow-up period, we will follow participants for a total duration of 60 days. Methemoglobin kinetic levels and efficacy outcomes will be collected.
1,881 studies on the registry are indexed under Critical Illness; 462 are open to participants now.
This study's planned enrollment of 34 is below the median of 90 across 979 interventional studies indexed under Critical Illness.
Browse Critical Illness studies →Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.
Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.
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Exclusion Criteria:
High dose inhaled nitric oxide starting at 250 ppm (not exceeding 300 ppm) , 40min, 4 times daily, from day 1 to day 5. Nitric oxide is delivered using a gas cylinder containing nitric oxide and nitrogen.
Drug: High dose inhaled nitric oxide · Other: standard therapy
Sham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group
Other: Sham treatment · Other: standard therapy
Inhaled nitric oxide starting at 250-300 ppm, 40min, every 6 hours, from day 1 to day 5. Nitric oxide is delivered using a gas cylinder containing nitric oxide and nitrogen.
Sham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group
Standard therapy pneumonia and critical illness
Peaks of methomoglobin
Continuous recording of MetHb and peaks of MetHb will be determined.
Time frame: From Day 1 to Day 5
Nitrogen dioxide level
Continuous measurement of nitrogen dioxide concentration in the inspiratory limb of breathing circuit
Time frame: From Day 1 to Day 5
Feasibility
Referral, recruitment, retention, compliance and follow-up completion rates of the study
Time frame: From enrollment to Day 60
Clinical cure rate of pneumonia
Clinical cure is assessed at test of cure (4 -11 days post end of treatment) and defined as resolution of clinical signs and symptoms of pneumonia compared with baseline, including a reduction in SOFA and CPIS scores, improvement or lack of progression in chest imaging, and no requirement for additional antibacterial treatment.
Time frame: From enrollment to test of cure day (4 -11 days post end of treatment)
Clinical improvement rate of pneumonia
Clinical improvement is assessed at end of treatment and defined as improvement in 2 or more clinical signs and symptoms of pneumonia compared with baseline, improvement or lack of progression of chest x-ray abnormalities, and no requirement for additional antibacterial treatment. Clinical signs and symptoms of pneumonia include new onset or worsening cough, purulent sputum or increased suction requirements, auscultation findings of pneumonia, dyspnea, tachypnea, or respiratory rate ≥ 30/min, hypoxemia, worsening gas exchange.
Time frame: Day 5
Microbiologic eradication rate
Absence of the baseline pathogen from tracheal aspiration or bronchoalveolar lavage fluid will be confirmed. If it is not possible to obtain an appropriate clinical specimen for culture and the patient has a successful clinical outcome, the response was presumed to be eradication.
Time frame: From enrollment to test of cure day (4 -11 days post end of treatment)
28-day all cause mortality
All cause mortality from enrollment to Day 28
Time frame: From enrollment to Day 28
60-day all cause mortality
All cause mortality from enrollment to Day 60
Time frame: From enrollment to Day 60
28-day ventilator free days
Successful liberation from mechanical ventilation should last more than 48 h without re-intubation in patients who have survived 28 days after randomization (extubation was counted from the last successful attempt in patients who have survived 28 days since randomization) and for patients ventilated for 28 days or more or who died before 28 days (irrespective of intubation status), the number of ventilator-free days was recorded at zero.
Time frame: From enrollment to Day 28
Days free from organ support in 28 days
Organ support includes mechanical ventilation, vasopressors and renal replacement therapy.
Time frame: From enrollment to Day 28
Blood stream infection
Positive blood culture with a pathogenic bacterium
Time frame: From enrollment to Day 28
Days free from antibiotics during hospitalization
Days free from antibiotics during hospitalization
Time frame: From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days
Acquisition of multidrug-resistant (MDR) infection or colonization
Multidrug-resistant infection is defined as pathogen acquiring non-susceptibility to at least one agent in three or more antibiotic categories
Time frame: From enrollment to Day 28
Hospital stay
Days from enrollment to the end of hospitalization
Time frame: From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days
ICU length of stay
ICU length of stay
Time frame: From enrollment to the day of ICU discharge or death, whichever comes earlier, assessed up to 60 days
Inflammatory markers
The test includes C reactive protein (CRP), procalcitonin (PCT), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF α), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10).
Time frame: From enrollment to test of cure (4-11 days post end of treatment)
Relapse rate
Relapse is assessed for patients with hospital-acquired pneumonia at 28-day follow-up after test of cure and defined as recurrence or new appearance of at least two of the three symptoms and signs (fever greater than 38 °C, leukocytosis or leukopenia, and purulent tracheobronchial secretions), along with a new or persistent infiltrate on chest radiography in a patient assessed as clinical cure at TOC.
Time frame: From enrollment to Day 28
Plan to share: Yes — All IPD that underlie results in a publication
Supporting information: Study protocol, Sap, Icf, Csr
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