High Dose Inhaled Nitric Oxide Therapy in Critically Ill Patients With Pneumonia: a Pilot, Double-blinded, Randomized, Controlled Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Peaks of methomoglobin
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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
Intervention: Sham treatment (Other)
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.
Intervention: High dose inhaled nitric oxide (Drug)
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.
Intervention: standard therapy (Other)
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
Intervention: standard therapy (Other)
Outcomes
Primary Outcomes
Peaks of methomoglobin
Time Frame: From Day 1 to Day 5
Continuous recording of MetHb and peaks of MetHb will be determined.
Secondary Outcomes
- 28-day all cause mortality(From enrollment to Day 28)
- ICU length of stay(From enrollment to the day of ICU discharge or death, whichever comes earlier, assessed up to 60 days)
- 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))
- 60-day all cause mortality(From enrollment to Day 60)
- 28-day ventilator free days(From enrollment to Day 28)
- Days free from organ support in 28 days(From enrollment to Day 28)
- Blood stream infection(From enrollment to Day 28)
- 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(From enrollment to Day 28)
- Hospital stay(From enrollment to the day of hospital discharge or death, whichever comes earlier, assessed up to 60 days)
- Inflammatory markers(From enrollment to test of cure (4-11 days post end of treatment))
- Relapse rate(From enrollment to Day 28)
Investigators
Lorenzo Berra, MD
Clinician Investigator, Associate Professor, Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute
Massachusetts General Hospital