iNO300 Therapy in Critically Ill Patients With Pneumonia

NCT06950294 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2025P000909
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Critical Illness; Pneumonia

Keywords

High dose inhaled nitric oxide; Pneumonia; Critical care; Methemoglobin

Outcome Measures

Primary Outcomes (1)

• Peaks of methomoglobin

  Continuous recording of MetHb and peaks of MetHb will be determined.

  From Day 1 to Day 5

Secondary Outcomes (15)

• Nitrogen dioxide level

  From Day 1 to Day 5

• Feasibility

  From enrollment to Day 60

• Clinical cure rate of pneumonia

  From enrollment to test of cure day (4 -11 days post end of treatment)

• Clinical improvement rate of pneumonia

  Day 5

• Microbiologic eradication rate

  From enrollment to test of cure day (4 -11 days post end of treatment)

Study Arms (2)

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.

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

Other: Sham treatment; Other: standard therapy

Interventions

Sham treatment OTHER

Sham intervention with the nitric oxide gas cylinder replaced by that containing only nitrogen and all other delivery procedures identical to the intervention group

Control group

standard therapy OTHER

Standard therapy pneumonia and critical illness

Control group; iNO300 group

High dose inhaled nitric oxide DRUG

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.

iNO300 group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (10)

• 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.

  PMID: 29178284 BACKGROUND

• Wolak 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.

  PMID: 39060420 BACKGROUND

• Miller 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.

  PMID: 22520076 BACKGROUND

• Wiegand 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.

  PMID: 33225304 BACKGROUND

• Strickland 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.

  PMID: 35623183 BACKGROUND

• Safaee 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.

  PMID: 34400339 BACKGROUND

• Wiegand 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.

  PMID: 33352464 BACKGROUND

• Valsecchi 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.

  PMID: 35852269 BACKGROUND

• Bartley 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.

  PMID: 32685229 BACKGROUND

• Okda 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.

  PMID: 39793728 BACKGROUND

MeSH Terms

Conditions

Critical Illness; Pneumonia

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Lorenzo Berra, MD

  Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenzo Berra, MD

CONTACT

617-726-3030; lberra@mgh.harvard.edu

Run Dong, MD

CONTACT

617-726-3030; rdong2@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Investigator, Associate Professor, Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute

Study Record Dates

• First Submitted: April 13, 2025
• First Posted: April 30, 2025
• Study Start: February 23, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 1 year after publication with no end date
• 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.

Locations

US (1)