iNO300 Therapy in Critically Ill Patients With Pneumonia

NCT ID: NCT06950294

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2026-12-31

Brief Summary

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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

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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

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Critical Illness Pneumonia

Keywords

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High dose inhaled nitric oxide Pneumonia Critical care Methemoglobin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

High dose inhaled nitric oxide

Intervention Type 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.

standard therapy

Intervention Type OTHER

Standard therapy pneumonia and critical illness

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

Group Type SHAM_COMPARATOR

Sham treatment

Intervention Type 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

standard therapy

Intervention Type OTHER

Standard therapy pneumonia and critical illness

Interventions

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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.

Intervention Type DRUG

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

Intervention Type OTHER

standard therapy

Standard therapy pneumonia and critical illness

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Lorenzo Berra, MD

Clinician Investigator, Associate Professor, Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lorenzo Berra, MD

Role: PRINCIPAL_INVESTIGATOR

Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital

Central Contacts

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Lorenzo Berra, MD

Role: CONTACT

Phone: 617-726-3030

Email: [email protected]

Run Dong, MD

Role: CONTACT

Phone: 617-726-3030

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 39793728 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29178284 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39060420 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22520076 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33225304 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35623183 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34400339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33352464 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35852269 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32685229 (View on PubMed)

Other Identifiers

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2025P000909

Identifier Type: -

Identifier Source: org_study_id