Clinical trial NCT06950294: iNO300 Therapy in Critically Ill Patients With Pneumonia
Official title: High Dose Inhaled Nitric Oxide Therapy in Critically Ill Patients With Pneumonia: a Pilot, Double-blinded, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Critical Illness
Pneumonia
Keywords: High dose inhaled nitric oxide
Pneumonia
Critical care
Methemoglobin
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2025-04-30
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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:

* Obvious signs of pregnancy (the third trimester) or active lactation.
* 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
* Documented history of left ventricular ejection fraction less than 30%
* Acute cardiogenic shock requiring inotropic or mechanical support with an ejection fraction less than 20%
* eGFR \< 30 ml/min/1.73m\^2 or use of continuous renal replacement therapy
* Platelet count less than 30,000/μl and/or high risk of bleeding
* A decision to do-not-resuscitate
* Enrollment in another experimental antimicrobial treatment protocol

Primary outcomes:
measure: Peaks of methomoglobin
timeFrame: From Day 1 to Day 5
Secondary outcomes:
measure: Nitrogen dioxide level
timeFrame: From Day 1 to Day 5
measure: Feasibility
timeFrame: From enrollment to Day 60
measure: Clinical cure rate of pneumonia
timeFrame: From enrollment to test of cure day (4 -11 days post end of treatment)
measure: Clinical improvement rate of pneumonia
timeFrame: Day 5
measure: Microbiologic eradication rate
timeFrame: From enrollment to test of cure day (4 -11 days post end of treatment)
measure: 28-day all cause mortality
timeFrame: From enrollment to Day 28
measure: 60-day all cause mortality
timeFrame: From enrollment to Day 60
measure: 28-day ventilator free days
timeFrame: From enrollment to Day 28
measure: Days free from organ support in 28 days
timeFrame: From enrollment to Day 28
measure: Blood stream infection
timeFrame: From enrollment to Day 28
measure: Days free from antibiotics during hospitalization
timeFrame: From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days
measure: Acquisition of multidrug-resistant (MDR) infection or colonization
timeFrame: From enrollment to Day 28
measure: Hospital stay
timeFrame: From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days
measure: ICU length of stay
timeFrame: From enrollment to the day of ICU discharge or death, whichever comes earlier, assessed up to 60 days
measure: Inflammatory markers
timeFrame: From enrollment to test of cure (4-11 days post end of treatment)
Other outcomes:
Locations:
Study officials:
affiliation: Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital
name: Lorenzo Berra, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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