Critical IllnessEarly Phase 1iNO300NCT06950294
iNO300 Therapy in Critically Ill Patients With Pneumonia
A Early Phase 1 study testing High dose inhaled nitric oxide and standard therapy in people with Critical Illness and Pneumonia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Pneumonia
- What is being tested?
- High dose inhaled nitric oxide and standard therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Feb 2026to Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- A decision to do-not-resuscitate (DNR)
- Enrollment in another experimental antimicrobial treatment protocol
- Patients for whom follow-up is expected to be impossible
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Run Dong, 6172563916, rdong2@mgh.harvard.edu
About this study
Official title: 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.
Read more
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
Read the 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.
- Conditions
- Critical Illness, Pneumonia
- Being tested
- High dose inhaled nitric oxide, Sham treatment, standard therapy
- Keywords
- High dose inhaled nitric oxide, Pneumonia, Critical care, Methemoglobin
- Medical subject headings
- Critical Illness, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High dose inhaled nitric oxideDrug
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 treatmentOther
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 therapyOther
Standard therapy pneumonia and critical illness
| Study group | Role | What they receive |
|---|---|---|
| iNO300 group | Experimental | 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. Receives: Drug: High dose inhaled nitric oxide; Other: standard therapy |
| Control group | Sham comparator | Sham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group Receives: Other: Sham treatment; Other: standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peaks of methomoglobin
Continuous recording of MetHb and peaks of MetHb will be determined.
Measured: From Day 1 to Day 5
Secondary outcomes (16)
Nitrogen dioxide level
Continuous measurement of nitrogen dioxide concentration in the inspiratory limb of breathing circuit
Measured: From Day 1 to Day 5
Feasibility
Referral, recruitment, retention, compliance and follow-up completion rates of the study
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: From enrollment to Day 28
60-day all cause mortality
All cause mortality from enrollment to Day 60
Measured: 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.
Measured: From enrollment to Day 28
Days free from organ support in 28 days
Organ support includes mechanical ventilation, vasopressors and renal replacement therapy.
Measured: From enrollment to Day 28
Blood stream infection
Positive blood culture with a pathogenic bacterium
Measured: From enrollment to Day 28
Days free from antibiotics during hospitalization
Days free from antibiotics during hospitalization
Measured: 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
Measured: From enrollment to Day 28
Hospital stay
Days from enrollment to the end of hospitalization
Measured: 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
Measured: 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).
Measured: 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.
Measured: From enrollment to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2025
- Study start23 Feb 2026
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Berra, MD, Massachusetts General Hospital
- Investigators
- Lorenzo Berra, MD, Principal investigator, Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06950294
- Sponsor's protocol ID
- 2025P000909
- Acronym
- iNO300
- Status last verified
- May 2026
- First submitted
- 13 Apr 2025
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication
Publications
Tal A, Greenberg D, Av-Gay Y, Golan-Tripto I, Feinstein Y, Ben-Shimol S, Dagan R, Goldbart AD. Nitric oxide inhalations in bronchiolitis: A pilot, randomized, double-blinded, controlled trial. Pediatr Pulmonol. 2018 Jan;53(1):95-102. doi: 10.1002/ppul.23905. Epub 2017 Nov 27.
PubMed 29178284Wolak T, Dicker D, Shifer Y, Grossman A, Rokach A, Shitrit M, Tal A. A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study. Sci Rep. 2024 Jul 26;14(1):17201. doi: 10.1038/s41598-024-68055-w.
PubMed 39060420Miller C, Miller M, McMullin B, Regev G, Serghides L, Kain K, Road J, Av-Gay Y. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012 Jul;11(4):324-31. doi: 10.1016/j.jcf.2012.01.003. Epub 2012 Apr 18.
PubMed 22520076Wiegand SB, Safaee Fakhr B, Carroll RW, Zapol WM, Kacmarek RM, Berra L. Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019. Crit Care Explor. 2020 Nov 16;2(11):e0277. doi: 10.1097/CCE.0000000000000277. eCollection 2020 Nov.
PubMed 33225304Strickland B, Albala L, Coffey EC, Carroll RW, Zapol WM, Ichinose F, Berra L, Harris NS. Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients. Am J Emerg Med. 2022 Aug;58:5-8. doi: 10.1016/j.ajem.2022.04.052. Epub 2022 May 4.
PubMed 35623183Safaee Fakhr B, Di Fenza R, Gianni S, Wiegand SB, Miyazaki Y, Araujo Morais CC, Gibson LE, Chang MG, Mueller AL, Rodriguez-Lopez JM, Ackman JB, Arora P, Scott LK, Bloch DB, Zapol WM, Carroll RW, Ichinose F, Berra L; Nitric Oxide Study Investigators. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia. Nitric Oxide. 2021 Nov 1;116:7-13. doi: 10.1016/j.niox.2021.08.003. Epub 2021 Aug 13.
PubMed 34400339Wiegand SB, Traeger L, Nguyen HK, Rouillard KR, Fischbach A, Zadek F, Ichinose F, Schoenfisch MH, Carroll RW, Bloch DB, Zapol WM. Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia. Redox Biol. 2021 Feb;39:101826. doi: 10.1016/j.redox.2020.101826. Epub 2020 Dec 11.
PubMed 33352464Valsecchi C, Winterton D, Safaee Fakhr B, Collier AY, Nozari A, Ortoleva J, Mukerji S, Gibson LE, Carroll RW, Shaefi S, Pinciroli R, La Vita C, Ackman JB, Hohmann E, Arora P, Barth WH Jr, Kaimal A, Ichinose F, Berra L; DELiverly oF iNO (DELFiNO) Network Collaborators. High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. Obstet Gynecol. 2022 Aug 1;140(2):195-203. doi: 10.1097/AOG.0000000000004847. Epub 2022 Jul 6.
PubMed 35852269Bartley BL, Gardner KJ, Spina S, Hurley BP, Campeau D, Berra L, Yonker LM, Carroll RW. High-Dose Inhaled Nitric Oxide as Adjunct Therapy in Cystic Fibrosis Targeting Burkholderia multivorans. Case Rep Pediatr. 2020 Jun 24;2020:1536714. doi: 10.1155/2020/1536714. eCollection 2020.
PubMed 32685229Okda M, Spina S, Safaee Fakhr B, Carroll RW. The antimicrobial effects of nitric oxide: A narrative review. Nitric Oxide. 2025 Apr;155:20-40. doi: 10.1016/j.niox.2025.01.001. Epub 2025 Jan 8.
PubMed 39793728
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose Inhaled Nitric Oxide Therapy in Critically Ill Patients With Pneumonia: a Pilot, Double-blinded, Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT06950294
- Acronym / sponsor ID
- iNO300 / 2025P000909
- Conditions
- Critical Illness, Pneumonia
- Keywords
- High dose inhaled nitric oxide, Pneumonia, Critical care, Methemoglobin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 23 Feb 2026 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 30 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| iNO300 group | Experimental | Drug: High dose inhaled nitric oxide, Other: standard therapyHigh 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. |
| Control group | Sham comparator | Other: Sham treatment, Other: standard therapySham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High dose inhaled nitric oxideInhaled 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. | Drug | iNO300 group |
| Sham treatmentSham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group | Other | Control group |
| standard therapyStandard therapy pneumonia and critical illness | Other | Control group, iNO300 group |
Primary outcome
Peaks of methomoglobin
Time frame: From Day 1 to Day 5
Continuous recording of MetHb and peaks of MetHb will be determined.
16 secondary outcomes
Nitrogen dioxide level
Time frame: From Day 1 to Day 5
Feasibility
Time frame: 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 improvement rate of pneumonia
Time frame: Day 5
Microbiologic eradication rate
Time frame: 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
60-day all cause mortality
Time frame: From enrollment to Day 60
28-day ventilator free days
Time frame: From enrollment to Day 28
Days free from organ support in 28 days
Time frame: From enrollment to Day 28
Blood stream infection
Time frame: 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
Acquisition of multidrug-resistant (MDR) infection or colonization
Time frame: 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
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
Time frame: From enrollment to test of cure (4-11 days post end of treatment)
Relapse rate
Time frame: From enrollment to Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Background: PubMed 29178284Tal A, Greenberg D, Av-Gay Y, Golan-Tripto I, Feinstein Y, Ben-Shimol S, Dagan R, Goldbart AD. Nitric oxide inhalations in bronchiolitis: A pilot, randomized, double-blinded, controlled trial. Pediatr Pulmonol. 2018 Jan;53(1):95-102. doi: 10.1002/ppul.23905. Epub 2017 Nov 27.
- Background: PubMed 39060420Wolak T, Dicker D, Shifer Y, Grossman A, Rokach A, Shitrit M, Tal A. A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study. Sci Rep. 2024 Jul 26;14(1):17201. doi: 10.1038/s41598-024-68055-w.
- Background: PubMed 22520076Miller C, Miller M, McMullin B, Regev G, Serghides L, Kain K, Road J, Av-Gay Y. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012 Jul;11(4):324-31. doi: 10.1016/j.jcf.2012.01.003. Epub 2012 Apr 18.
- Background: PubMed 33225304Wiegand SB, Safaee Fakhr B, Carroll RW, Zapol WM, Kacmarek RM, Berra L. Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019. Crit Care Explor. 2020 Nov 16;2(11):e0277. doi: 10.1097/CCE.0000000000000277. eCollection 2020 Nov.
- Background: PubMed 35623183Strickland B, Albala L, Coffey EC, Carroll RW, Zapol WM, Ichinose F, Berra L, Harris NS. Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients. Am J Emerg Med. 2022 Aug;58:5-8. doi: 10.1016/j.ajem.2022.04.052. Epub 2022 May 4.
- Background: PubMed 34400339Safaee Fakhr B, Di Fenza R, Gianni S, Wiegand SB, Miyazaki Y, Araujo Morais CC, Gibson LE, Chang MG, Mueller AL, Rodriguez-Lopez JM, Ackman JB, Arora P, Scott LK, Bloch DB, Zapol WM, Carroll RW, Ichinose F, Berra L; Nitric Oxide Study Investigators. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia. Nitric Oxide. 2021 Nov 1;116:7-13. doi: 10.1016/j.niox.2021.08.003. Epub 2021 Aug 13.
- Background: PubMed 33352464Wiegand SB, Traeger L, Nguyen HK, Rouillard KR, Fischbach A, Zadek F, Ichinose F, Schoenfisch MH, Carroll RW, Bloch DB, Zapol WM. Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia. Redox Biol. 2021 Feb;39:101826. doi: 10.1016/j.redox.2020.101826. Epub 2020 Dec 11.
- Background: PubMed 35852269Valsecchi C, Winterton D, Safaee Fakhr B, Collier AY, Nozari A, Ortoleva J, Mukerji S, Gibson LE, Carroll RW, Shaefi S, Pinciroli R, La Vita C, Ackman JB, Hohmann E, Arora P, Barth WH Jr, Kaimal A, Ichinose F, Berra L; DELiverly oF iNO (DELFiNO) Network Collaborators. High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. Obstet Gynecol. 2022 Aug 1;140(2):195-203. doi: 10.1097/AOG.0000000000004847. Epub 2022 Jul 6.
- Background: PubMed 32685229Bartley BL, Gardner KJ, Spina S, Hurley BP, Campeau D, Berra L, Yonker LM, Carroll RW. High-Dose Inhaled Nitric Oxide as Adjunct Therapy in Cystic Fibrosis Targeting Burkholderia multivorans. Case Rep Pediatr. 2020 Jun 24;2020:1536714. doi: 10.1155/2020/1536714. eCollection 2020.
- Background: PubMed 39793728Okda M, Spina S, Safaee Fakhr B, Carroll RW. The antimicrobial effects of nitric oxide: A narrative review. Nitric Oxide. 2025 Apr;155:20-40. doi: 10.1016/j.niox.2025.01.001. Epub 2025 Jan 8.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lorenzo Berra, MD principal investigator
Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing High dose inhaled nitric oxide and standard therapy in people with Critical Illness and Pneumonia, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lorenzo Berra, MD (617-726-3030, lberra@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peaks of methomoglobin (time frame: From Day 1 to Day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06950294, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.