iNO300 Therapy in Critically Ill Patients With Pneumonia (iNO300)

May 20, 2026 updated by: Lorenzo Berra, MD, Massachusetts General Hospital

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

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:

  • Receive iNO treatment starting at 250 ppm, not exceeding 300 ppm, 40 min, every 6 hours, from day 1 to day 5
  • Be followed up for 60 days

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

34

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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%
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: iNO300 group
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.
Other: standard therapy
Standard therapy pneumonia and critical illness
Drug: High dose inhaled nitric oxide
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 Comparator: Control group
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: standard therapy
Standard therapy pneumonia and critical illness
Other: Sham treatment
Sham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peaks of methomoglobin
Time Frame: From Day 1 to Day 5
Continuous recording of MetHb and peaks of MetHb will be determined.
From Day 1 to Day 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nitrogen dioxide level
Time Frame: From Day 1 to Day 5
Continuous measurement of nitrogen dioxide concentration in the inspiratory limb of breathing circuit
From Day 1 to Day 5
Feasibility
Time Frame: From enrollment to Day 60
Referral, recruitment, retention, compliance and follow-up completion rates of the study
From enrollment to Day 60
Clinical cure rate of pneumonia
Time Frame: From enrollment to test of cure day (4 -11 days post end of treatment)
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.
From enrollment to test of cure day (4 -11 days post end of treatment)
Clinical improvement rate of pneumonia
Time Frame: Day 5
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.
Day 5
Microbiologic eradication rate
Time Frame: From enrollment to test of cure day (4 -11 days post end of treatment)
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.
From enrollment to test of cure day (4 -11 days post end of treatment)
28-day all cause mortality
Time Frame: From enrollment to Day 28
All cause mortality from enrollment to Day 28
From enrollment to Day 28
60-day all cause mortality
Time Frame: From enrollment to Day 60
All cause mortality from enrollment to Day 60
From enrollment to Day 60
28-day ventilator free days
Time Frame: From enrollment to Day 28
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.
From enrollment to Day 28
Days free from organ support in 28 days
Time Frame: From enrollment to Day 28
Organ support includes mechanical ventilation, vasopressors and renal replacement therapy.
From enrollment to Day 28
Blood stream infection
Time Frame: From enrollment to Day 28
Positive blood culture with a pathogenic bacterium
From enrollment to Day 28
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
Days free from antibiotics during hospitalization
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
Time Frame: From enrollment to Day 28
Multidrug-resistant infection is defined as pathogen acquiring non-susceptibility to at least one agent in three or more antibiotic categories
From enrollment to Day 28
Hospital stay
Time Frame: From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days
Days from enrollment to the end of hospitalization
From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days
ICU length of stay
Time Frame: From enrollment to the day of ICU discharge or death, whichever comes earlier, assessed up to 60 days
ICU length of stay
From enrollment to the day of ICU discharge or death, whichever comes earlier, assessed up to 60 days
Inflammatory markers
Time Frame: From enrollment to test of cure (4-11 days post end of treatment)
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).
From enrollment to test of cure (4-11 days post end of treatment)
Relapse rate
Time Frame: From enrollment to Day 28
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.
From enrollment to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Lorenzo Berra, MD, Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2026

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

April 13, 2025

First Submitted That Met QC Criteria

April 24, 2025

First Posted (Actual)

April 30, 2025

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025P000909

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in a publication

IPD Sharing Time Frame

Beginning 1 year after publication with no end date

IPD Sharing Access Criteria

A proposal that describes planned analyses must be submitted to the principal investigator via email. Data sharing agreement should be reached, documented and signed.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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